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Caffeic Acid and Its Derivatives: Antimicrobial Drugs toward Microbial Pathogens
Abstract
Caffeic acid is a plant-derived compound that is classified as hydroxycinnamic acid which contains both phenolic and acrylic functional groups. Caffeic acid has been greatly employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses. Similarly, several derivatives of caffeic acid such as sugar esters, organic esters, glycosides, and amides have been chemically synthesized or naturally isolated as potential antimicrobial agents. To overcome the issue of water insolubility and poor stability, caffeic acid and its derivative have been utilized either in conjugation with other bioactive molecules or in nanoformulation. Besides, caffeic acid and its derivatives have also been applied in combination with antibiotics or photoirradiation to achieve a synergistic mode of action. The present review describes the antimicrobial roles of caffeic acid and its derivatives exploited either in free form or in combination or in nanoformulation to kill a diverse range of microbial pathogens along with their mode of action. The chemistry employed for the synthesis of the caffeic acid derivatives has been discussed in detail as well.
... It is widely distributed in edible fruits and vegetables (such as tomatoes, olives, coffee beans, potatoes, carrots), propolis and medicinal plants such as wormwood, eucommia, artichoke, honeysuckle, dandelion. 7 CA and its metabolic derivatives in vivo, such as CA phenylethyl ester, have a wide range of biological activities, for instance, anti-inflammatory, antioxidant, antitumor, anticell proliferation, liver antifibrotic effect. 7,8 CA is mainly absorbed through the intestine, with a small burden on the liver and kidney, and has a high distribution in the blood and kidney. ...
... 7 CA and its metabolic derivatives in vivo, such as CA phenylethyl ester, have a wide range of biological activities, for instance, anti-inflammatory, antioxidant, antitumor, anticell proliferation, liver antifibrotic effect. 7,8 CA is mainly absorbed through the intestine, with a small burden on the liver and kidney, and has a high distribution in the blood and kidney. 9 This is the basis for its therapeutic effect in the kidney. ...
... CA has been widely used as an alternative therapy against microbial pathogenic mechanisms and chronic infections induced by microorganisms such as bacteria, fungi, and viruses. 7,10 As in kidney-related diseases, it has been reported that CA derivatives, such as CA phenethyl ester or rosmarinic acid, have a protective effect from ischemia/reperfusion injury in kidney 11 and can ameliorate RTF. 12 Veeren et al 13 also reported that oral administration of CA performs nephroprotective effects, but no more detail molecular mechanism has been explored. It is necessary to explore the molecular mechanism of CA in RTF, in order to find out reliable therapeutic targets, reduce and even reverse the damage. ...
Background: Renal tubulointerstitial fibrosis (RTF) is a progressive kidney condition characterized by the formation of fibrotic tissue. Caffeic acid (CA), a key component of the medicinal plant Antirhea borbonica, shows promise as a potential treatment for renal fibrosis. Here, we investigated the nephroprotective effect of CA in RTF and its underlying mechanisms. Methods: RTF was induced in rats through unilateral ureteral obstruction (UUO), followed by intraperitoneal administration of CA for 5 days. We assessed kidney weight/body weight (KW/BW) ratio, serum creatinine (Scr), blood urea nitrogen (BUN), 24-h urine protein (UP), and performed histological examinations. We also analyzed the expression of fibrosis-related proteins. Genes associated with RTF and CA were identified using public databases. A protein-protein interaction (PPI) network and molecular docking studies were conducted. Results: CA treatment significantly reduced the KW/BW ratio, levels of Scr, BUN, and 24-h UP, indicating improved kidney function in UUO-induced RTF rats. Histological examination revealed reduced fibrotic changes. CA administration also led to decreased collagen deposition and downregulation of fibrosis-related protein expression. CA administration also led to decreased collagen deposition and downregulation of fibrosis-related protein expression. The PPI network analysis showed significant differential expression of 13 genes between the fibrosis and normal groups. Notably, EGFR and MAPK14 were strongly associated with CA, and CA treatment downregulated EGFR and MAPK14 protein expression in UUO rats. Conclusion: CA exhibits substantial nephroprotective effects in UUO-induced RTF rats by modulating key genes EGFR and MAPK14, and MAPK signaling pathway.
... Second, TcCSE is a member of the phenylpropanoid pathway and, in Arabidopsis, is responsible for hydrolyzing caffeoyl shikimate into the hydroxycinnamic acid (HCA) caffeate (caffeic acid) [124]. HCAs and derivatives thereof are well-known antimicrobial secondary metabolites involved in various plant-pathogen interactions [83,86,[125][126][127]. Together, these results indicate TcCSE could be a potentially important and as yet uncharacterized gene involved in cacao's defense response. ...
... The hydroxycinnamic acid amide clovamide indirectly inhibits the growth of three species of Phytophthora, including P. palmivora, in cacao [83]. And lastly, caffeic acid and its derivatives both directly and indirectly inhibit many pathogens, among them P. palmivora and P. megakarya [86,127]. ...
... Second, it could be the case that caffeic acid was converted into lignin via sinapic acid [134], which would not be detected using our metabolite extraction protocol. And lastly, caffeic acid could have been converted into one or more caffeic acid derivatives that are difficult to predict and quantify [127]. Together, our results indicate that TcCSE and caffeic acid are potentially important components of the cacao plant defense, though we so far lack a complete understanding of expression time course and the fate of resulting metabolites. ...
Background
Plants have complex and dynamic immune systems that have evolved to resist pathogens. Humans have worked to enhance these defenses in crops through breeding. However, many crops harbor only a fraction of the genetic diversity present in wild relatives. Increased utilization of diverse germplasm to search for desirable traits, such as disease resistance, is therefore a valuable step towards breeding crops that are adapted to both current and emerging threats. Here, we examine diversity of defense responses across four populations of the long-generation tree crop Theobroma cacao L., as well as four non-cacao Theobroma species, with the goal of identifying genetic elements essential for protection against the oomycete pathogen Phytophthora palmivora.
Results
We began by creating a new, highly contiguous genome assembly for the P. palmivora-resistant genotype SCA 6 (Additional file 1: Tables S1-S5), deposited in GenBank under accessions CP139290-CP139299. We then used this high-quality assembly to combine RNA and whole-genome sequencing data to discover several genes and pathways associated with resistance. Many of these are unique, i.e., differentially regulated in only one of the four populations (diverged 40 k–900 k generations). Among the pathways shared across all populations is phenylpropanoid biosynthesis, a metabolic pathway with well-documented roles in plant defense. One gene in this pathway, caffeoyl shikimate esterase (CSE), was upregulated across all four populations following pathogen treatment, indicating its broad importance for cacao’s defense response. Further experimental evidence suggests this gene hydrolyzes caffeoyl shikimate to create caffeic acid, an antimicrobial compound and known inhibitor of Phytophthora spp.
Conclusions
Our results indicate most expression variation associated with resistance is unique to populations. Moreover, our findings demonstrate the value of using a broad sample of evolutionarily diverged populations for revealing the genetic bases of cacao resistance to P. palmivora. This approach has promise for further revealing and harnessing valuable genetic resources in this and other long-generation plants.
... Although their concentration is relatively low, they may still contribute to the overall health benefits of Echinacea Due to the important role of Echinacea and the significance of its chemical constituents, various studies have employed biotechnological methods to enhance the yield of certain bioactive compounds, with a particular focus on the caffeic derivatives group [1,[18][19]22,24]. The Figure 2 illustrates the molecular structures of compounds derived from Echinacea, demonstrating their potential production through biotechnological methods [22]. ...
... The Figure 2 illustrates the molecular structures of compounds derived from Echinacea, demonstrating their potential production through biotechnological methods [22]. In particular, the compounds echinacoside, cynarin, and chlorogenic acid are highlighted as important chemical components with substantial potential for further growth in the pharmaceutical and cosmetics industries [8,18,22]. Biotechnological approaches offer a promising avenue for the sustainable and controlled synthesis of these bioactive compounds, ensuring a reliable source for pharmaceutical and nutraceutical industries. ...
The Echinacea genus is known for its medicinal properties, particularly its immune-stimulating effects. Thus, it makes a significant focus of phytochemical research. This literature review provides a short overview of the chemical constituents found within the Echinacea genus, with a primary emphasis on E. purpurea, E. angustifolia, and E. pallida, the three most extensively studied species. The constituents discussed include alkamides, polysaccharides, glycoproteins, phenolic compounds, and flavonoids, which are derived from various plant parts, such as roots, stems, leaves, and flowers. Detailed insights into the structural diversity, distribution, and biological significance of these compounds are presented. Additionally, key differentiating markers for species identification are highlighted, aiding researchers and herbal practitioners in understanding the chemical complexities of Echinacea species. This review offers information for the development of herbal medicines and supplements, shedding light on the potential therapeutic benefits of chemical constituents of these species.
... Drying processes for commercial instant coffee usually reduce its water content by less than 5% by mass. The remaining composition of the blend is a mixture of carbohydrates, proteins, flavor oils, phosphates, and melanoidins (Gloess et al., 2013;Khan et al., 2021;Shofinita et al., 2024). ...
... Although no coffee extraction samples showed antimicrobial activity, it is known that phenolic compounds, like caffeic acid, an ordinary phenolic compound found in coffee beans, have a large antimicrobial activity against bacteria, viruses, and fungi (Khan et al., 2021). This class of compounds alters the rigidity of the cell wall, which results in the loss of cell integrity. ...
Cold brew is a method of coffee extraction that uses low temperature, preserving the volatile compounds of coffee. Freeze-drying allows the preservation of coffee features and nutritional value. The aim of this study was to evaluate the effects of different cryoprotectants in cold brew extracts as a basis for freeze-dried coffee production. Thus, the Coffea arabica extracts and the soluble coffee were characterized concerning caffeine content, antioxidant capacity, total phenolic compounds, and antimicrobial activity to verify the potential of this method. The extracts did not show antimicrobial activity with a high soluble solid content. It was observed that the cold extraction methods were efficient regarding the caffeine content, antioxidant capacity, and total phenolic compounds. Freeze-dried coffees also did not show antimicrobial activity, and they maintained the water and humidity activity standards. In general, cryoprotectants displayed an unfavorable influence on the extract and freeze-dried coffee in the analyses performed. The coffee extract without cryoprotectants had a higher antioxidant capacity (88.12%) and content of phenolic compounds (7.74 mg AG/mL of the coffee extract). Only for the analyses of soluble solids, the cryoprotectants mannitol and fructose showed promising results (14.03 °Brix, 14.40 °Brix, 11.33 °Brix, respectively). Thus, for the analyses conducted, the cryoprotectants did not lead to significant advantages for this process.
... Caffeic acid (CA), also known as 3,4-dihydroxy cinnamic acid, is an organic compound that has two functional groups (phenolic hydroxyl and acrylic acid) [1]. Caffeic acid derivatives refer to a large class of compounds that contain caffeic acid structural units [2]. ...
... The type of sugar in caffeoyl glycosides can be determined by the chemical shift and coupling constant observed for the characteristic end-substrate hydrogen signal of the sugar. In general, the end-substrate proton signals of sugar in 1 The relative configuration of the glycoside bond was determined by 1 H-NMR and the coupling constants of C 1 -H and C 2 -H. In most monosaccharides, such as glucose and their glycosides, the two-sided angle between the end-group proton and H-2 is 180 • because H-2 on the sugar is located on the upright bond when the oxygen on the end group is β-oriented, and the 3 J H1,H2 value is approximately 6~8 Hz. ...
In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.
... It was found that Enterobacter hormaechei cells experienced a significant decrease in intracellular ATP levels upon treatment with vanillic acid [27]. Similarly, caffeic acid, a polyphenol found in WGHa, disrupted ATP synthesis by down-regulating the activity of H + -ATPase, consequently impeding the growth of S. aureus and K. pneumoniae [28]. Additionally, ginger phenolics reduced intracellular ATP synthesis in E. coli by inhibiting the activity of F1Fo ATP synthase [29]. ...
... Molecules 2023,28, 7981 ...
Walnut green husks (WGHs), by-products of walnut production, are believed to possess antimicrobial properties, making them a potential alternative to antibiotics. In this study, the antibacterial activities of three extracts, derived from WGH, against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli were investigated, and the antibacterial mechanisms of an anhydrous ethanol extract of WGH (WGHa) were examined. The results showed that WGHa exhibited inhibitory effects on all tested bacteria. The ultrahigh-performance liquid chromatography–tandem mass spectrometry analysis revealed that the major active compounds present in WGHa were terpenoids, phenols, and flavonoids. Treatment with WGHa resulted in the leakage of intracellular ions and alkaline phosphatase; a reduction in intracellular ATP content, ATPase activity, and nucleic acid content; as well as cellular metabolic viability. The transmission electron microscopy images showed varying degrees of cell deformation and membrane damage following WGHa treatment. The transcriptome sequencing and differentially expressed gene enrichment analyses revealed an up-regulation in pathways associated with RNA degradation, translation, protein export, and oxidative phosphorylation. Conversely, pathways involved in cell movement and localization, as well as cell wall organization and carbohydrate transport, were found to be down-regulated. These findings suggest that WGHa alters cell membrane permeability and causes damage to the cell wall. Additionally, WGHa interferes with cellular energy metabolism, compromises RNA integrity, and induces DNA replication stress, consequently inhibiting the normal growth and proliferation of bacteria. These findings unveiled the antimicrobial mechanisms of WGHa, highlighting its potential application as an antibiotic alternative.
... CFA and other phenolic compounds are involved in plants' defense mechanism against insects, pathogens, animals (biotic stresses), and environmental conditions, such as excess water, drought, low and high temperatures, salinity, heavy metals, and ultraviolet radiation (abiotic stresses) [8,9]. Numerous in vitro and in vivo studies have shown that CFA has many biological properties, including anti-inflammatory [10][11][12], anticancer [1,[13][14][15], antibacterial [16][17][18], antiviral [19,20], antidiabetic [21,22], hepatoprotective [23][24][25], and cardioprotective activity [26,27]. The presence of a catechol group with a chain of α,β-unsaturated carboxylic acids in the chemical structure of CFA affects its antioxidant properties. ...
Spectroscopic studies (FT-IR, Raman, 1H, and 13C NMR, UV-VIS) of caffeic acid (CFA) and its conjugates, i.e., caftaric acid (CTA), cichoric acid (CA), and cynarin (CY), were carried out. The antioxidant activity of these compounds was determined by a superoxide dismutase (SOD) activity assay and the hydroxyl radical (HO•) inhibition assay. The cytotoxicity of these compounds was performed on DLD-1 cell lines. The molecules were theoretically modeled using the B3LYP-6-311++G(d,p) method. Aromaticity indexes (HOMA, I6, BAC, Aj), HOMO and LUMO orbital energies and reactivity descriptors, NBO electron charge distribution, EPS electrostatic potential maps, and theoretical IR and NMR spectra were calculated for the optimized model systems. The structural features of these compounds were discussed in terms of their biological activities.
... To identify a novel structural class for DHFR inhibition, caffeic acid was selected as a lead to design novel derivatives as in our previous investigation aimed at identifying novel compounds from natural sources that could inhibit DHFR; caffeic acid demonstrated significant activity and favorable binding scores [18]. Although numerous studies have been conducted to assess the antimicrobial and anticancer properties of caffeic acid, the lack of understanding regarding its mechanism of action and its interaction with DHFR has significantly impeded the utilization of caffeic acid as a lead and the discovery of promising novel derivatives based on caffeic acid [19][20][21][22][23]. Screening various heterocyclic compounds for the development of novel derivatives of caffeic acid, we found that compounds containing nitrogen and oxygen atoms have demonstrated significant biological efficacy [24]. ...
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (−9.9; −70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π–cation bond with Phe92, and a salt bridge with the polar residue Asp27.
... Caffeic acid, another compound identified in AECO, also exhibits promising antimicrobial activity. According to Khan et al. [39], this phenolic compound alters membrane permeability, inhibits enzymatic activity, and damages the DNA of bacterial and fungal pathogens. Furthermore, Kępa et al. [40] found that the combination of caffeic acid with the antibiotics, erythromycin, clindamycin, cefoxitin, and vancomycin, induced promising synergistic activity against strains of S. aureus isolated from infectious wounds, reinforcing the hypothesis that natural products can enhance the effect of commercial antibiotics against resistant microorganisms. ...
The global antibiotic resistance crisis highlights the inappropriate use of medicines by the population and the lack of development of new antimicrobial agents. According to various studies, natural products are promising alternatives for combating bacterial resistance and treating infectious diseases. Accordingly, the present study aimed to analyze the chemical composition and evaluate the antibacterial and antibiotic potential of an aqueous extract of Cordia oncocalyx Allemão (AECO). Phytochemical analyses were performed using high-performance liquid chromatography equipped with a diode array detector (HPLC-DAD). The minimum inhibitory concentration (MIC) was used to evaluate the antibacterial activity of C. oncocalyx against conventional and multidrug-resistant (MDR) bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). According to HPLC-DAD analysis, the following compounds could be identified in the aqueous extract of C. oncocalyx: luteolin (3.07 AE 0.04 mg/g), caffeic acid (1.05 AE 0.03 mg/g), ellagic acid (0.62 AE 0.05 mg/g), and quercetin (0.58 AE 0.01). AECO did not exhibit antibacterial activity when administered alone (MIC >512 μg/mL). However, when combined with gentamicin, ampicillin, and norfloxacin, AECO potentiated the action of these antibiotics against the multi-resistant strains of P. aeruginosa and S. aureus. Although clinical relevance was not revealed by the in vitro tests against pathogenic bacteria, AECO can combined with commercial antibiotics to improve their antibacterial effects. Future studies focusing on the mechanisms of action of the compounds isolated from C. oncocalyx and toxicological tests are fundamental.
... Caffeic acid is one of the ingredients in cosmetic (dermatological) preparations that enhances the antimicrobial effect of these preparations, even if they do not have a direct antibacterial and antifungal effect [58]. Caffeic acid has significantly been employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses [60]. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive phytochemical, and its derivatives are often present in cosmetic formulations and can be considered "safe" and "natural" in the context of cosmetic production [61]. ...
The group of innovative ingredients in cosmetic preparations includes bio-ferments (Bs), which are characterized by high bioactivity and biocompatibility, and one of the plants rich in bioactive compounds that has a beneficial effect on the skin and the body is Silybum marianum. Bio-ferments obtained from this plant are becoming increasingly useful as active ingredients in cosmetics. In the present study, four different bio-ferments were obtained by fermentation of pomace (B-P), extract (B-E), oil (B-O), and seeds (B-S) of milk thistle. Their biodegradability (%B), total polyphenols content (Folin-Ciocalteu method), and antimicrobial, antioxidant (DPPH, ABTS, and FRAP methods), chelating (Fe 2+ ions), and reduction (Cu 2+ and Fe 3+ ions) properties, as well as the acidity, were evaluated. The contact angle using the sessile drop method was assessed to investigate bio-ferments' impact on skin wettability. Finally, the content of selected phenolic acids in the Bs was evaluated using the HPLC method, while the lactic acid (LA) content was assessed using the GC-MS method. All bio-ferments were characterized by high polyphenols content (13.56 ± 0.10-15.28 ± 0.12 mmol GA/L B), chelating (0.08 ± 0.01-0.17 ± 0.01 mmol Fe 2+ /L B) and antioxidant activity (DPPH method, 2.41 ± 0.01-3.53 ± 0.01 mmol Tx/L B), and reducing Cu 2+ and Fe 3+ ions. Gallic acid, protocatechuic acid, caffeic acid, neochlorogenic acid, coumaric acid, and LA were identified in Bs. The most increased antibacterial activity for B-P was observed for a strain of Staphylococcus aureus (MIC = 250 µL/mL) and Pseudomonas aeruginosa (MIC = 250 µL/mL). Simultaneously, B-S demonstrated the highest inhibitory effects against Escherichia coli (MIC = 125 µL/mL), emphasizing the varied antimicrobial profiles of these bio-ferments against different bacterial strains. Research on aerobic biodegradation demonstrated a high level of degradation (%B= 60 ± 1-65 ± 3), and all Bs were categorized as readily degradable according to the OECD classification. Citation: Kucharska, E.; Grygorcewicz, B.; Spietelun, M.; Olszewska, P.; Bobkowska, A.; Ryglewicz, J.; Nowak, A.; Muzykiewicz-Szymańska, A.; Kucharski, Ł.; Pełech, R. Potential
... Caffeic acid is one of the ingredients in cosmetic (dermatological) preparations that enhances the antimicrobial effect of these preparations, even if they do not have a direct antibacterial and antifungal effect [58]. Caffeic acid has significantly been employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses [60]. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive phytochemical, and its derivatives are often present in cosmetic formulations and can be considered "safe" and "natural" in the context of cosmetic production [61]. ...
The group of innovative ingredients in cosmetic preparations includes bio-ferments (Bs), which are characterized by high bioactivity and biocompatibility, and one of the plants rich in bioactive compounds that has a beneficial effect on the skin and the body is Silybum marianum. Bio-ferments obtained from this plant are becoming increasingly useful as active ingredients in cosmetics. In the present study, four different bio-ferments were obtained by fermentation of pomace (B-P), extract (B-E), oil (B-O), and seeds (B-S) of milk thistle. Their biodegradability (%B), total polyphenols content (Folin-Ciocalteu method), and antimicrobial, antioxidant (DPPH, ABTS, and FRAP methods), chelating (Fe 2+ ions), and reduction (Cu 2+ and Fe 3+ ions) properties, as well as the acidity, were evaluated. The contact angle using the sessile drop method was assessed to investigate bio-ferments' impact on skin wettability. Finally, the content of selected phenolic acids in the Bs was evaluated using the HPLC method, while the lactic acid (LA) content was assessed using the GC-MS method. All bio-ferments were characterized by high polyphenols content (13.56 ± 0.10-15.28 ± 0.12 mmol GA/L B), chelating (0.08 ± 0.01-0.17 ± 0.01 mmol Fe 2+ /L B) and antioxidant activity (DPPH method, 2.41 ± 0.01-3.53 ± 0.01 mmol Tx/L B), and reducing Cu 2+ and Fe 3+ ions. Gallic acid, protocatechuic acid, caffeic acid, neochlorogenic acid, coumaric acid, and LA were identified in Bs. The most increased antibacterial activity for B-P was observed for a strain of Staphylococcus aureus (MIC = 250 µL/mL) and Pseudomonas aeruginosa (MIC = 250 µL/mL). Simultaneously, B-S demonstrated the highest inhibitory effects against Escherichia coli (MIC = 125 µL/mL), emphasizing the varied antimicrobial profiles of these bio-ferments against different bacterial strains. Research on aerobic biodegradation demonstrated a high level of degradation (%B= 60 ± 1-65 ± 3), and all Bs were categorized as readily degradable according to the OECD classification. Citation: Kucharska, E.; Grygorcewicz, B.; Spietelun, M.; Olszewska, P.; Bobkowska, A.; Ryglewicz, J.; Nowak, A.; Muzykiewicz-Szymańska, A.; Kucharski, Ł.; Pełech, R. Potential
... The extracts containing such a class of molecule have been extensively tested for their antimicrobial properties, as revised by Khan et al. in 2021 [30]. Moreover, increased antimicrobial activity has been observed for caffeic acid conjugated with other active molecules or vehiculized in nanoparticles [30][31][32][33][34][35][36]. ...
Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today’s central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol–ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.
... Quercetin, kaempferol, and caffeic acid were most likely the compounds responsible for the remarkable antimicrobial activity of the BBE5 sample because these were present in the highest amount in this, have activity on both Gram-positive and Gram-negative bacterial strains, and the first two sometimes acted synergistically [105][106][107]. In addition, Qian et al. [108] revealed that vanillic acid, which had the highest concentration in this sample (BBE5), possessed antimicrobial activity against S. aureus and E. coli. ...
Bee bread has received attention due to its high nutritional value, especially its phenolic composition, which enhances life quality. The present study aimed to evaluate the chemical and antimicrobial properties of bee bread (BB) samples from Romania. Initially, the bee bread alcoholic extracts (BBEs) were obtained from BB collected and prepared by Apis mellifera carpatica bees. The chemical composition of the BBE was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and the total phenols and flavonoid contents were determined. Also, a UHPLC-DAD-ESI/MS analysis of phenolic compounds (PCs) and antioxidant activity were evaluated. Furthermore, the antimicrobial activity of BBEs was evaluated by qualitative and quantitative assessments. The BBs studied in this paper are provided from 31 families of plant species, with the total phenols content and total flavonoid content varying between 7.10 and 18.30 mg gallic acid equivalents/g BB and between 0.45 and 1.86 mg quercetin equivalents/g BB, respectively. Chromatographic analysis revealed these samples had a significant content of phenolic compounds, with flavonoids in much higher quantities than phenolic acids. All the BBEs presented antimicrobial activity against all clinical and standard pathogenic strains tested. Salmonella typhi, Candida glabrata, Candida albicans, and Candida kefyr strains were the most sensitive, while BBEs’ antifungal activity on C. krusei and C. kefyr was not investigated in any prior research. In addition, this study reports the BBEs’ inhibitory activity on microbial (bacterial and fungi) adhesion capacity to the inert substratum for the first time.
... Because of its strong antioxidant action, it helps plants tolerate stress e ciently. It participates in the control of pathogen attacks by fungi, bacteria, and viruses, as well as the management of salinity, ion toxicity, drought, and heavy metal stress 35 . These results are the same as those of Anuradha who said that infecting P. edulis fruit with the telosma mosaic virus increased the total amount of phenolics in the fruit 36 . ...
The present study focused on the impact of infection with the tobacco mosaic virus (TMV) Specifically, changes in phytochemicals and gene activity related to pathogenesis-related and the phenylpropanoid pathway genes in tomato plants (Solanum lycopersicum L.) during a period of 2-to-14-day post inoculation (dpi). According to TEM investigation and coat protein sequence analysis, the purified TMV Egyptian AM isolate (PP133743) has a rod-shaped structure with a diameter of around 110 nm. The RT-qPCR analysis revealed that PR-1 showed an initial increase after TMV infection, as seen in the time-course analysis. In contrast, PR-2 was consistently elevated throughout the infection, suggesting a stronger reaction to the virus and suppressing PAL expression at 6 to 14 dpi. The expression levels of HQT and CHS transcripts exhibited alternating patterns of upregulation and downregulation at different time intervals. The HPLC and GC-MS analysis of control and TMV-infected tomato extracts revealed that different phenolic, flavonoid, and fatty acid compounds could be increased (such as naringenin, rutin, flavone, ferulic acid, and pyrogallol) or decreased (such as salicylic acid and chlorogenic acid) after TMV infection. The ability of TMV to inhibit most polyphenolic compounds could potentially accelerate the viral life cycle. Consequently, working to increase such suppressed compounds in tomato plants could be important for developing the management of plant viral infections.
... The major compounds were determined as 3,4-dihydroxy benzoic acid, quercetin-3,4'-O-di-β-glucopyranoside, caffeic acid, citrulline, 3-hydroxy-3methyl glutaric acid, acacetin, citraconic acid, isookanin-7-glucoside, esculin, myricetin, luteolin-7-O-glucoside, malic acid, and kaempferol-7-neohesperidoside. Several studies have documented the potential antibacterial activity of these bioactive compounds in fenugreek extract [54][55][56][57][58]. ...
Owing to the spread of resistance between pathogenic bacteria, searching for novel compounds with antibacterial activity is essential. Here, we investigated the potential antibacterial activity of Greek clover or Trigonella foenum-graecum herb extract on Salmonella typhimurium clinical isolates. The chemical profile of the herb was initially determined using LC-ESI-MS/MS, which explored 36 different compounds. Interestingly, the fenugreek extract possessed antibacterial action in vitro with minimum inhibitory concentrations of 64 to 512 µg/mL. The potential mechanism of action was studied by elucidating the effect of the fenugreek extract on the membrane properties of S. typhimurium bacteria, including the inner and outer membrane permeability and membrane integrity. Remarkably, the fenugreek extract had detrimental effects on the membrane properties in 40–60% of the isolates. Moreover, the in vivo antibacterial action was studied using a gastrointestinal infection model with S. typhimurium bacteria. Interestingly, the fenugreek extract (200 mg/kg) improved the infection outcomes in the tested mice. This was represented by the noteworthy decrease (p < 0.05) in the bacterial count in the small intestine and caecum tissues. The survival rate of the fenugreek-extract-treated mice significantly increased compared to the S. typhimurium-infected group. Additionally, there was an improvement in the histological and immunohistochemical features of tumor necrosis factor-alpha. In addition, using an ELISA and qRT-PCR, there was an improvement in the proinflammatory and oxidative stress markers in the fenugreek-extract-treated group. Consequently, fenugreek extract should be investigated further on other food pathogens.
... All phenolic acids investigated in the present study, caffeic acid [129,130], chlorogenic acid [131,132], ellagic acid [133,134], and gallic acid [135,136], were found to have significant antimicrobial activity. In addition, flavonoids have multiple bacteria cellular targets due to their chemical structure. ...
Plant waste materials are important sources of bioactive compounds with remarkable health-promoting benefits. In particular, industrial by-products such as mango peels are sustainable sources of bioactive substances, with antioxidant, enzymatic, and antimicrobial activity. Appropriate processing is essential to obtain highly bioactive compounds for further use in generating value-added products for the food industry. The objective of the study was to investigate and compare the biological activity of compounds from fresh and dried mango peels obtained by different conventional methods and unconventional extraction methods using supercritical fluids (SFE). The highest total phenolic content (25.0 mg GAE/g DW) and the total content of eight phenolic compounds (829.92 µg/g DW) determined by LC-MS/MS were detected in dried mango peel extract obtained by the Soxhlet process (SE). SFE gave the highest content of proanthocyanidins (0.4 mg PAC/g DW). The ethanolic ultrasonic process (UAE) provided the highest antioxidant activity of the product (82.4%) using DPPH radical scavenging activity and total protein content (2.95 mg protein/g DW). Overall, the dried mango peels were richer in bioactive compounds (caffeic acid, chlorogenic acid, gallic acid, catechin, and hesperidin/neohesperidin), indicating successful preservation during air drying. Furthermore, outstanding polyphenol oxidase, superoxide dismutase (SOD), and lipase activities were detected in mango peel extracts. This is the first study in which remarkable antibacterial activities against the growth of Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) were evaluated by determining the microbial growth inhibition rate after 12 and 24 h incubation periods for mango peel extracts obtained by different methods. Ethanolic SE and UAE extracts from dried mango peels resulted in the lowest minimum inhibitory concentrations (MIC90) for all bacterial species tested. Mango peels are remarkable waste products that could contribute to the sustainable development of exceptional products with high-added value for various applications, especially as dietary supplements.
... Accumulating evidence has shown that natural products have become promising agents for pathogen resistance, such as luteolin (32), sanguinarine (33), brevilin A (13), and dioscin (34). Caffeic acid (3,4-dihydroxy cinnamic acid) is a major phenolic compound present in several plant species such as fruits, wine, coffee, olive oil, and legumes (14,15), which exhibits a wide variety of biological activities, including anti-oxidative (16), anti-fibrosis (17), anti-inflammatory (18), anti-tumor (19), Table S1 for survival data. EV (empty vector). ...
Mitochondria play roles in the resistance of Caenorhabditis elegans against pathogenic bacteria by regulating mitochondrial unfolded protein response (UPRmt). Caffeic acid (CA) (3,4-dihydroxy cinnamic acid) is a major phenolic compound present in several plant species, which exhibits biological activities such as antioxidant, anti-fibrosis, anti-inflammatory, and anti-tumor properties. However, whether caffeic acid influences the innate immune response and the underlying molecular mechanisms remains unknown. In this study, we find that 20 µM caffeic acid enhances innate immunity to resist the Gram-negative pathogen Pseudomonas aeruginosa infection in C. elegans. Meanwhile, caffeic acid also inhibits the growth of pathogenic bacteria. Furthermore, caffeic acid promotes host immune response by reducing the bacterial burden in the intestine. Through genetic screening in C. elegans, we find that caffeic acid promotes innate immunity via the transcription factor ATFS-1. In addition, caffeic acid activates the UPRmt and immune response genes for innate immune response through ATFS-1. Our work suggests that caffeic acid has the potential to protect patients from pathogen infection.
... Bajko et al. showed that 5-O-caffeoylquinic acid has interesting antibacterial activity against both Gram-positive and Gram-negative bacteria, with MICs between 5 and 10 mg/mL [44]. In addition, studies have proven the antibacterial activity of quercetin, apigenin, luteolin, and caffeic acid and their derivative compounds [45][46][47][48]. Interestingly, the mode of action of plant compounds on bacteria is complex and may vary depending on different factors. ...
Medicinal plants are considered a major source for discovering novel effective drugs. To our knowledge, no studies have reported the chemical composition and biological activities of Moroccan Lactuca saligna extracts. In this context, this study aims to characterize the polyphenolic compounds distributed in hydro-methanolic extracts of L. saligna and evaluate their antioxidant and antibacterial activities; in addition, in silico analysis based on molecular docking and ADMET was performed to predict the antibacterial activity of the identified phenolic compounds. Our results showed the identification of 29 among 30 detected phenolic compounds with an abundance of dicaffeoyltartaric acid, luteolin 7-glucoronide, 3,5-di-O-caffeoylquinic acid, and 5-caffeoylquinic acid with 472.77, 224.30, 196.79, and 171.74 mg/kg of dried extract, respectively. Additionally, antioxidant activity assessed by DPPH scavenging activity, ferric reducing antioxidant power (FRAP) assay, and ferrous ion-chelating (FIC) assay showed interesting antioxidant activity. Moreover, the results showed remarkable antibacterial activity against Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes with minimum inhibitory concentrations between 1.30 ± 0.31 and 10.41 ± 0.23 mg/mL. Furthermore, in silico analysis identified three compounds, including Apigenin 7-O-glucuronide, Quercetin-3-O-glucuronide, and 3-p-Coumaroylquinic acid as potent candidates for developing new antibacterial agents with acceptable pharmacokinetic properties. Hence, L. saligna can be considered a source of phytochemical compounds with remarkable activities, while further in vitro and in vivo studies are required to explore the main biological activities of this plant.
... It is derived from fruits and vegetables. Previous studies have shown that caffeic acid and its derivatives could exert various functions, including antioxidant, antiinflammatory, anti-cancer, and immunoregulatory functions [19][20][21]. Caffeic acid derivatives could reduce the consumption of SOD via scavenging ROS, and inhibiting the activities of xanthine oxidase and nitric oxide synthase. The present study investigated whether WSY6 could protect melanocytes from oxidative stress-induced damage and its potential mechanisms. ...
Purpose
Vitiligo is a chronic depigmentation disease caused by a loss of functioning melanocytes and melanin from the epidermis. Oxidative stress-induced damage to melanocytes is key in the pathogenesis of vitiligo. WSY6 is a caffeic acid derivative synthesized from epigallocatechin-3-gallate (EGCG). This study is to investigate whether the new chemical WSY6 protected melanocytes from H2O2-induced cell damage and to elucidate the underlying molecular mechanism.
Patients and methods
The present study compared the antioxidative potential of WSY6 with EGCG in hydrogen peroxide (H2O2)-treated PIG1 cells. Western blotting was used to study the protein expression of cyto-c, cleaved-caspase3, cleaved-caspase9, and the activation of MAPK family members, including p38, ERK1/2, JNK and their phosphorylation in melanocytes. ROS assay kit to detect intracellular reactive oxygen species production; CCK8 and lactate dehydrogenase leak assay to detect cytotoxicity.
Results
EGCG and WSY6 ameliorated H2O2-induced oxidative stress damage in PIG1 cells in a does-dependent manner, while WSY6 was much more effective. WSY6 reduced cellular ROS production, cytochrome c release, downregulated caspase-3 and caspase-9 activation. MAPK pathway signaling including phosphorylated p38, ERK and JNK were observed under oxidative stress and can be much protected by pre-treatment of WSY6.
Conclusion
These results indicated that WSY6 could be a more powerful antioxidant than EGCG and protect melanocytes against oxidative cytotoxicity.
... The caffeic acid MIC/MBC values in the case of the other tested bacteria and the strain of Candida albicans exceeded 6900 µM (1200 µg/mL). The results of the obtained caffeic acid antimicrobial activity match the results of former studies with corresponding test conditions [9]. Even if various semi-synthetic caffeic acid derivatives have already been studied, according to available reports, no research on antimicrobial activity has been performed with caffeic acid quaternary phosphanium bromide derivatives until now. ...
Caffeic acid (CA) is one of the most abundant natural compounds present in plants and has a broad spectrum of beneficial pharmacological activities. However, in some cases, synthetic derivation of original molecules can expand their scope. This study focuses on the synthesis of caffeic acid phosphanium derivatives with the ambition of increasing their biological activities. Four caffeic acid phosphanium salts (CAPs) were synthesized and tested for their cytotoxic, antibacterial, antifungal, and amoebicidal activity in vitro, with the aim of identifying the best area for their medicinal use. CAPs exhibited significantly stronger cytotoxic activity against tested cell lines (HeLa, HCT116, MDA-MB-231 MCF-7, A2058, PANC-1, Jurkat) in comparison to caffeic acid. Focusing on Jurkat cells (human leukemic T cell lymphoma), the IC50 value of CAPs ranged from 0.9 to 8.5 μM while IC50 of CA was >300 μM. Antimicrobial testing also confirmed significantly higher activity of CAPs against selected microbes in comparison to CA, especially for Gram-positive bacteria (MIC 13–57 μM) and the yeast Candida albicans (MIC 13–57 μM). The anti-Acanthamoeba activity was studied against two pathogenic Acanthamoeba strains. In the case of A. lugdunensis, all CAPs revealed a stronger inhibitory effect (EC50 74–3125 μM) than CA (>105 µM), while in A. quina strain, the higher inhibition was observed for three derivatives (EC50 44–291 μM). The newly synthesized quaternary phosphanium salts of caffeic acid exhibited selective antitumor action and appeared to be promising antimicrobial agents for topical application, as well as potential molecules for further research.
... Yet, the avor of cigar tobacco is created and determined by the climate (temperature, sunlight duration, and rainfall) and soil environment of different geographical regions [9,10]. The accumulation of various metabolites is the fundamental reason for the formation of cigar avor pro les [11][12][13]. At the same time, the quality of agronomic traits determine the yield of cigar tobacco [14,15]. ...
Background Despite the flourishing international trade of cigar tobacco leaves and China's significant cigar market, there has been limited systematic reports on the main characteristics of cigar tobacco leaves from different regions of China. These characteristics include the agro-ecological adaptability of cigar tobacco to major tobacco producing areas in China and the characteristics of cigar metabolite accumulation among different regions in China. Therefore, the cigar industry developed in various provinces in China lacks reference for agricultural and ecological adaptability assessment, reference for the selection of planting areas, and reference databases for cigar and tobacco metabolite characteristics.
Results The agronomic traits of the cigar tobacco varieties across the four regions displayed considerable value for harvesting. All four regions possessed the necessary agricultural conditions for conducting cigar tobacco agroecological adaptability research. A total of 793 metabolites were detected and annotated, including 80 volatile metabolites, 209 semi-volatile metabolites, and 504 endogenous metabolites. These comprised 113 alcohols, 97 sugars, 73 amino acids, 56 ketones, 45 alkanes, and 26 aldehydes. By selecting for VIP≥1, FC＞2, or FC＜0.5, 36.65% of metabolites exhibited differences between at least two experimental points. A preliminary reference database encompassing characteristics of metabolites accumulation of cigar tobacco was constructed, providing a reference for future metabolite research in various domestic cigar tobacco producing regions.
Conclusions Positive correlations between cigar tobacco yield and primary metabolite accumulation were observed. Prolonged high-temperature and rainy conditions were found to be detrimental to the accumulation of secondary metabolites responsible for aroma in cigar tobacco. Shifang, Sichuan (N: 31.127°, E: 104.168°) demonstrated significant advantages in the accumulation of various aroma-related metabolites such as aldehydes, sugars and amino acids. It was selected as a reference point for subsequent comparisons of metabolite accumulation levels in cigar tobacco, offering insights and references for the cultivation site selection and in-depth metabolite research of cigar tobacco in China.
The Runchang‐Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra‐high‐performance liquid chromatography coupled with mass spectrometry (UPLC–MS) and high‐resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top‐three‐scoring receptor‐small‐molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds.
Secondary metabolites, polyphenols, are widespread in the entire kingdom of plants. They contain one or more hydroxyl groups that have a variety of biological functions in the natural environment. These uses include polyphenols in food, beauty products, dietary supplements, and medicinal products and have grown rapidly during the past 20 years. Antimicrobial polyphenols are described together with their sources, classes, and subclasses. Polyphenols are found in different sources, such as dark chocolate, olive oil, red wine, almonds, cashews, walnuts, berries, green tea, apples, artichokes, mushrooms, etc. Examples of benefits are antiallergic, antioxidant, anticancer agents, anti-inflammatory, antihypertensive, and antimicrobe properties. From these sources, different classes of polyphenols are helpful for the growth of internal functional systems of the human body, providing healthy fats, vitamins, and minerals, lowering the risk of cardiovascular diseases, improving brain health, and rebooting our cellular microbiome health by mitochondrial uncoupling. Among the various health benefits of polyphenols (curcumin, naringenin, quercetin, catechin, etc.) primarily different antimicrobial activities are discussed along with possible future applications. For polyphenols and antimicrobial agents to be proven safe, adverse health impacts must be substantiated by reliable scientific research as well as in vitro and in vivo clinical data. Future research may be influenced by this evaluation.
Herein, we describe the synthesis of the proposed structure of the caffeamide alkaloid bassiamide A. The amide moiety of bassiamide A was readily formed via an amide coupling reaction between caffeic acid and the known N ‐(3‐aminopropyl)‐3‐methylbutanamide. However, the spectral data of the synthesized bassiamide A did not agree with that of a previous study. The structure of the synthesized bassiamide A was confirmed using combined two‐dimensional NMR analysis. Extended analyses of the bioactivity of the synthesized bassiamide A revealed its efficacy in protecting dopaminergic neurons from MPP ⁺ ‐induced neurotoxicity in Caenorhabditis elegans . Additionally, treatment with bassiamide A notably ameliorated the impaired food‐sensing ability and locomotion of Caenorhabditis elegans , suggesting a protective effect on the functionality of dopaminergic neurons.
Pacific white shrimp without and with prior pulsed electric field (PEF) followed by soaking in 0.5 and 1 % soursop leaf extract (SLE) without and with vacuum impregnation (VI) for 2 cycles were prepared. After soaking, PEF-treated shrimp in 1% SLE in combination with VI (PEF-SLE1-VI), 13 phenolic compounds in shrimp meat were found. When the changes in quality of shrimp with varying treatments were monitored, PEF-SLE1-VI showed the lowest alterations during 15 days of storage. It was the only sample having the microbial load below the maximum limit after 15 days and showed the lowest melanosis with likeness score defined as “like slightly”. Such treatment retarded microbial growth, particularly psychrotrophic bacteria and Pseudomonas. Overall, prior PEF treatment of whole shrimp before soaking in 1% SLE with the aid of VI maintained quality and lengthened shelf life via inhibiting melanosis and deterring microbial proliferation in refrigerated shrimp.
Chitooligosaccharide (COS) is a derivative of chitosan, which is a natural macromolecular compound. COS has been shown effects in an inflammatory response. Recent reports show that COS derivatives have enhanced anti‐inflammatory activity by inhibiting intracellular signals. Evaluation of the anti‐inflammatory effect of caffeic acid conjugated COS chain (CA‐COS) was performed in this study. The effects of CA‐COS on the inflammatory response were demonstrated in lipopolysaccharide‐stimulated RAW264.7 macrophages. The results showed that CA‐COS inhibited nitric oxide (NO) production and downregulated the gene expression of nitric oxide synthase (iNOS), and cytokines such as tumor necrosis factor‐alpha (TNF‐α), IL‐1β, and IL‐6 without cytotoxic effect. In addition, western blot analysis showed that CA‐COS inhibits the protein expression of iNOS and nuclear factor kappa B (NF‐kB), including p50 and p65, and mitogen‐activated protein kinase (MAPK) signaling pathways. Collectively, these results provide clear evidence for the anti‐inflammatory mechanism of CA‐COS that show great potential as a novel agent for the prevention and therapy of inflammatory diseases.
Phenolic compounds (polyphenols/phenolics) are the plants’ secondary metabolites produced for defense purposes. The ubiquitous nature of phenolics describes their functional diversity. They have noteworthy impact on different physiological and metabolic processes of plant. These compounds act as antimicrobial, antifungal, and antioxidant agents that intercept microbial invasions. Phenolics also play structural role in plants and provide integrity, vigor, and vitality to plant cells. Plant phenolic defense system includes physical alterations (suberization or lignification), metabolic changes (de novo biosynthesis of pathogenesis-related proteins), synthesis, and accretion of phenylpropanoid-derived metabolites (phytoalexins). Phenolics have dual function and act as both attractants and repellents for organisms around plants. They protect plants from the damage caused by pathogens and other microbes. Phenolic compounds have various defensive mechanisms that provide shield to plants for invading pathogens. Moreover, being weak acids, phenolics such as anthocyanins, hydroxycinnamic acid (HCAs), and flavonoids have free radicals scavenging potential that is accumulative in plants under stress and prevents plants from oxidative stress. In addition, phenolic compounds such as flavonoids are an important rhizospheric signaling molecules that attract symbiotic (Rhizobium) as well as pathogenic microbes (Agrobacterium). Thus, they are important in developing plant–microbial interactions.
Drought is the most common abiotic stress that hinders plantgrowth. To clarify the changes in the growth and metabolism of Panax notoginseng following drought stress, here the effects of drought stress on the growth and metabolism of P. notoginseng are investigated using gas chromatography–mass spectrometry based on a widely targeted metabolomic approach. We conducted drought stress treatments (DS) and re‐watering treatments after drought stress (RW) with no drought stress as the control group. The results showed that DS treatment significantly inhibited biomass accumulation and root development of P. notoginseng . Single saponin Rg 1 and total saponin in the roots were the highest in the control group, while the total saponins in the leaves were the highest in DS. A total of 120 metabolites were identified using metabolomics and they were classified into eight categories. The metabolites of P. notoginseng under DS were significantly different from the control and RW treatment. Caffeic acid was significantly enriched in all comparison groups, suggesting its important role in the drought resistance of P. notoginseng . Enrichment analysis of differential metabolites showed that the ATP‐binding cassette (ABC) transporters, the metabolic pathway of valine, leucine, and isoleucine were closely associated with the drought resistance of P. notoginseng . We also verified that significantly upregulated differential metabolites such as 5‐aminolevulinic acid (5‐ALA) and quinic acid can enhance the drought resistance of P. notoginseng through exogenous application.
A current alternative for sustainable development through green chemistry is the replacement of synthetic compounds with natural ones through the superior capitalization of natural resources, with numerous applications in different fields. The benefits of walnuts (Juglans regia L.) and elderberries (Sambucus nigra L.) have been known since ancient times, due to the presence of phytochemicals such as flavonoids, polyphenols, carotenoids, alkaloids, nitrogen-containing compounds, tannins, steroids, anthocyanins, etc. These active compounds have multiple biological activities for human health, including benefits that are antibacterial, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, antihypertensive, neuroprotective, etc. Like other medicinal plants, the walnut and the elderberry possess important phytosanitary properties (antibacterial, antifungal, and insecticidal) and their extracts can also be used as environmentally safe biopesticides, with the result that they constitute a viable and cheap alternative to environmentally harmful synthetic products. During recent years, walnut by-products and elderberries have attracted the attention of researchers, and investigations have focused on the species’ valuable constituents and active properties. Comparing the information from the literature regarding the phytochemical profile and biological activities, it is highlighted that, apart from the predominant specific compounds, the walnut and the elderberry have common bioactive compounds, which come from six classes (phenols and derivatives, flavonoids, hydroxycinnamic acids, tannins, triterpenoids, and phytosteroids), and act on the same microorganisms. From this perspective, the aim of this review is to provide an overview of the bioactive compounds present in the different constitutive parts of walnut by-products and elderberries, which present a specific or common activity related to human health and the protection of agricultural crops in the context of sustainable development.
CA is a plant derivative with antibacterial and antiviral pharmacological effects, however, the therapeutic effect of CA on Klebsiella pneumonia and its mechanism study is still unclear. A rat KP model was established in vitro, a pneumonia cell model was established in vivo, the histopathological changes in the lungs were observed by HE staining after CA treatment, the expression of relevant inflammatory factors was detected by ELISA, the changes in the expression of proteins related to the AhR‐Src‐STAT3‐IL‐10 signaling pathway were detected by Western blot and immunofluorescence in the lungs, and the interactions between the proteins were verified by COIP relationship. The results showed that CA was able to attenuate the injury and inflammatory response of lung tissues, and molecular docking showed that there were binding sites between CA and AhR, and COIP demonstrated that AhR interacted with both STAT3 and Ser. In addition, CA was able to up‐regulate the expression levels of pathway‐related proteins of AhR, IL‐10, p‐Src, and p‐STAT3, and AhR knockdown was able to reduce LPS‐induced inflammatory responses and up‐regulate pathway‐related proteins, whereas CA treatment of AhR‐knockdown‐treated A549 cells did not show any statistically significant difference compared with the AhR knockdown group, demonstrating that CA exerts its pharmacological effects. These findings elucidated the mechanism of CA in the treatment of KP and demonstrated that CA is a potential therapeutic agent for KP.
The emergence of antibiotic resistance is a serious global health problem. There is an incessant demand for new antimicrobial drugs and materials that can address this global issue from different angles. Dendritic hydrogels have appeared as a promising strategy. A family of bifunctional amphiphilic carbosilane dendrimers was designed and employed as nanosized cross-linking points for the synthesis of high-swelling hydrogels using the highly efficient Thiol–Ene click reaction for their preparation. Both stoichiometric and off-stoichiometric conditions were studied, generating hydrogels with pendant hydroxyl or alkene moieties. These hydrogels were found to be tunable antibacterial materials. They can easily be postmodified with relevant antibiotic moieties through covalent attachment on the hydroxyl or alkene pendant groups, generating ammonium-decorated networks with temperature and pH-responsive properties. Additionally, they can efficiently encapsulate drugs with poor solubility in water, like ciprofloxacin, and perform a sustained release over time, as demonstrated in preliminary assays against Staphylococcus aureus.
Colorectal cancer (CRC) is generally characterized by a high prevalence of Fusobacterium nucleatum ( F. nucleatum ), a spindle‐shaped, Gram‐negative anaerobe pathogen derived from the oral cavity. This tumor‐resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, F. nucleatum can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non‐antibiotic approaches to eradicate F. nucleatum and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic‐organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat F. nucleatum and F. nucleatum biofilms. This review summarizes the latest advancements in anti‐ F. nucleatum research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC.
The rising trend of antibiotic-resistant infections around the world and the low antimicrobials development pipeline volume are necessitating continued efforts in the search for novel treatment options. The prominent success from fungi and bacteria as sources of antibiotics has long motivated widespread efforts in the search for antibacterial compounds from other natural sources including plants. This review aimed at appraising the approaches and outcomes from studies commissioned to evaluate the antibacterial activities of crude plant extracts and phytochemicals. Notably, the existing traditional practices provided the greatest motivation in screening for antibacterial properties of plants, whereby the need to validate ethnomedically reported potentials formed a crucial objective. Moreover, choices of experimental techniques to address different objectives were largely dependent on the prevailing access to resources, facilities, and technical skills. The lack of streamlined guidelines dedicated to testing of crude plant extracts have resulted into broad methodological variations and lack of a standardized classification system for antibacterial activities exhibited by plant extracts. Furthermore, libraries of 128 extracts from different plant species and 122 phytochemicals substantially active against the Escherichia coli and Klebsiella pneumoniae were assembled. This enabled the elucidation of existing patterns between the Minimum Inhibitory Concentrations (MICs) and studied plant families, plant tissues, extractants, phytochemical classes, as well as the rules of drug-likeness, penetration and accumulation. The insights provided in this review will potentially impart the ongoing efforts with improved experimental designs, inspire ideas for further studies and contribute to successful hunting for new antibacterial chemical scaffolds via in silico approaches.
Graphical abstract
Candida albicans is an opportunistic yeast that causes most fungal infections. C. albicans has become increasingly resistant to antifungal drugs over the past decade. Our study focused on the identification of pure natural compounds for the development of antifungal medicines. A total of 15 natural compounds from different chemical families (cinnamic derivatives, aromatic phenols, mono- and sesquiterpenols, and unclassified compounds) were screened in this study. Among these groups, hinokitiol (Hi), a natural monoterpenoid extracted from the wood of the cypress family, showed excellent anti-C. albicans activity, with a MIC value of 8.21 µg/mL. Hi was selected from this panel for further investigation to assess its antifungal and anti-inflammatory properties. Hi exhibited significant antifungal activity against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. It also reduced biofilm formation and hyphal growth. Treatment with Hi protected Caenorhabditis elegans against infection with C. albicans and enhanced the expression of antimicrobial genes in worms infected with C. albicans. Aside from its antifungal activities against C. albicans, Hi challenge attenuated the LPS-induced expression of pro-inflammatory cytokines (IL-6, IL-1β, and CCL-2) in macrophages. Overall, Hi is a natural compound with antifungal and anti-inflammatory properties, making Hi a promising platform with which to fight against fungal infections.
The fungus Pochonia chlamydosporia colonizes plant-parasitic nematode eggs, but also may suppress soilborne phytopathogenic fungi. This study aimed to assess the impact of four P. chlamydosporia isolates on the mycelial growth of Rhizoctonia solani in laboratory settings and the effect of these isolates in the management of R. solani in table beet under greenhouse conditions, including the combination or not of the isolate Pc-13 with a wine industry by-product. In laboratory, the isolates Pc-10, Pc-11, and Pc-13 of P. chlamydosporia inhibited R. solani mycelial growth in the assays of direct confrontation and production of volatile metabolites. In the greenhouse, all isolates of P. chlamydosporia increased table beet seedling emergence. However, only isolate Pc-13 reduced damping-off in the seedlings. The combination of the fungus with wine industry by-product reduced disease incidence in comparison to the control, but the effect was similar to applying the residue alone. Pochonia chlamydosporia isolate Pc-13 and the wine industry by-product have potential to manage damping-off in table beet.
The Bougainvillea glabra or bougainvillea is a climbing plant native from South America belonging to the Nyctaginaceae family. The bougainvillea is recognized worldwide for its horticultural importance, due to the color of its bracts, commonly known as “flowers,” made up of bracts, which are the striking parts, and the true flowers, which are white and small. Bougainvillea is widely known in traditional medicine to treat respiratory diseases such as cough, asthma, and bronchitis, gastrointestinal diseases, also for its antibacterial and insecticidal capacity. The antimicrobial potential of the involucre of this plant has not been studied, despite research showing a high phytochemical presence of secondary metabolites such as alkanes, phenols, terpenes, and betalains. This review compiles information about the traditional uses of B. glabra, its botanical description, ecological relevance, phytochemistry, antimicrobial and antibiofilm activity, such as the toxicology of bracts and flowers.
Adiantum philippenseLinn (Pteridiaceae), commonly known as “Goyalelata” which has been traditionally used to cure of different diseases including dysentery, ulcers, fevers, cooling and elephantiasis. This study aims to summarize the phytoconstituents reported for A. philippenseand its pharmacological activities as well as further in-silicomolecular dynamics studies to identify active compounds against COX-2 enzyme as potent analgesic. The data for this study were collected using online databases such as Google Scholar, PubMed, Scopus and Web of Science. Previous studies have established that a number of phytochemicals have been identified from this plant including phenolic compounds (caffeic acid, chlorogenic acid, phloroglucino, esculetin), flavonoids (rutin, quercetin, luteolin), terpenoids (ursolic acid, botulin, carvone and glycyrrhetinic acid). Literature study demonstrated that A. philipensehas the potential analgesic, antioxidant, antimicrobial, cytotoxic and hepatoprotective effects in both in-vivoand in-vitrotest systems. The plant can act as suitable candidate for the biosynthesis of nanoparticles and application as a therapeutic purpose. The molecular docking analysis of itsreported phytoconstituents with CoX-2 showed that quercetin, and luteolin exhibited the most favorable binding affinity with a value of -8.1 and -8.0 kcal/mol, respectively. Further molecular dynamics study revealed that quercetin was the most promising anti-inflammatory compounds present inA. philippense confirmed by the RMSD, RMSF, Rg, SASA and hydrogen bond analysis. In summary, it is proved that A. philippenseone of the potential traditional medicinal fern that possess bioactive compounds which couldbe useful in the prevention of pain and inflammation
There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.
Simple phenylpropanoids are a large group of natural products with primary C6-C3 skeletons. They are not only important biomolecules for plant growth but also crucial chemicals for high-value industries, including fragrances, nutraceuticals, biomaterials, and pharmaceuticals. However, with the growing global demand for simple phenylpropanoids, direct plant extraction or chemical synthesis often struggles to meet current needs in terms of yield, titre, cost, and environmental impact. Benefiting from the rapid development of metabolic engineering and synthetic biology, microbial production of natural products from inexpensive and renewable sources provides a feasible solution for sustainable supply. This review outlines the biological activities of simple phenylpropanoids, compares their biosynthetic pathways in different species (plants, bacteria, and fungi), and summarises key research on the microbial production of simple phenylpropanoids over the last decade, with a focus on engineering strategies that seem to hold most potential for further development. Moreover, constructive solutions to the current challenges and future perspectives for industrial production of phenylpropanoids are presented.
The chloroform extract of Origanum majorana exhibited high antibacterial and antifungal activities against 12 bacterial and 4 fungal strains; therefore, it was subjected to bioassay-guided isolation to afford six compounds (1–6). The structures were determined via one- and two-dimensional nuclear magnetic spectroscopy and high-resolution electrospray ionization mass spectrometry experiments. The compounds were identified as furanonaphthoquinones [majoranaquinone (1), 2,3-dimethylnaphtho[2,3-b]furan-4,9-dione (2)], diterpenes [19-hydroxyabieta-8,11,13-trien-7-one (3), 13,14-seco-13-oxo-19-hydroxyabieta-8-en-14-al (4)], and flavonoids [sterubin (5) and majoranin (6)]. Compounds 1 and 2 were first obtained from a natural source and compounds 3 and 4 were previously undescribed. Majoranaquinone (1) exhibited a high antibacterial effect against 4 Staphylococcus, 1 Moraxella, and 1 Enterococcus strains (MIC values between 7.8 μM and 1 mM). In the efflux pump inhibition assay, majoranaquinone (1) showed substantial activity in Escherichia coli ATCC 25922 strain. Furthermore, 1 was found to be an effective biofilm formation inhibitor on E. coli ATCC 25922 and E. coli K-12 AG100 bacteria. Our findings proved that bioactivities of majoranaquinone (1) significantly exceed those of the essential oil constituents; therefore, it should also be considered when assessing the antimicrobial effects of O. majorana.
In this study, we investigated the structures of lanthanide (Eu(III), Dy(III), and Gd(III)) complexes with p-coumaric (p-CAH2) and caffeic (CFAH3) acids using the FTIRKBr, FTIRATR, and Raman spectroscopic methods. The compositions of the solid phase caffeinates and p-coumarates were obtained on the basis of the amounts of hydrogen and carbon determined using an elemental analysis. The degree of hydration and the thermal decomposition of each compound were examined via a thermal analysis of TG, DTG, and DSC. Antioxidant spectroscopic tests were performed using the DPPH (1,1-diphenyl-2-picrylhydrazyl radical), FRAP (ferric reducing antioxidant activity), and ABTS (2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (diammonium salt radical cation) methods. The antimicrobial activity of each compound against Escherichia coli, Bacillus subtilis, and Candida albicans was investigated. The electrical properties of the liposomes which mimicked the microbial surfaces formed in the electrolyte containing the tested compounds were also investigated. The above biological properties of the obtained complexes were compared with the activities of p-CAH2 and CFAH3. The obtained data suggest that lanthanide complexes are much more thermally stable and have higher antimicrobial and antioxidant properties than the ligands (with the exception of CFAH3 in the case of antioxidant activity tests). The Gd(III) complexes revealed the highest biological activity among the studied lanthanide complexes.
The 3,4-dihydroxy cinnamic acid derivatives are known as caffeic acid derivatives are widely distributed in the plant kingdom. The most common caffeic acid derivatives are esters of caffeic acid with quinic acid and the caffeic acid phenylethyl ester (CAPE). CAPE is an active component of propolis from honeybee hives and is widely known for its antiviral, anti-inflammatory, and immunomodulatory properties. Caffeic acid esters also have the ability to alter the redox state and induce apoptosis. Since CAPE, an ester derivative of Caffeic acid, a naturally occurring active compound having antimicrobial, anti-inflammatory and antioxidant / anticancer properties, we decided to make a library of compounds using various permutation and combinations to come up with novel ether, ester and hybrid derivatives of Caffeic acid wherein Caffeic acid would be esterified with various other compounds and check if such compounds can have antimicrobial, anti-inflamma-tory and antioxidant / anticancer properties. Several novel esters of caffeic acid were synthesized and tested for potential antibacterial activity. This combinatorial synthesis of novel caffeic ester derivatives can be a useful approach to generate potent chemotherapeutic agents in developing new drug candidates.
The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into a phosphatidylcholine ethanol solution under magnetic stirring. Size distribution and morphology of ethosome were investigated by photon correlation spectroscopy, small-angle X-ray spectroscopy, and cryogenic transmission electron microscopy, while the entrapment capacity of caffeic acid was evaluated by high-performance liquid chromatography. Caffeic acid stability in ethosome was compared to the stability of the molecule in water, determined by mass spectrometry. Ethosome dispersion was thickened by poloxamer 407, obtaining an ethosomal gel that was characterized for rheological behavior and deformability. Caffeic acid diffusion kinetics were determined by Franz cells, while its penetration through skin, as well as its antioxidant activity, were evaluated using a porcine skin membrane–covered biosensor based on oxygen electrode. Ethosome mean diameter was ≈200 nm and almost stable within three months. The entrapment of caffeic acid in ethosome dramatically prolonged drug stability with respect to the aqueous solution, being 77% w/w in ethosome after six months, while in water, an almost complete degradation occurred within one month. The addition of poloxamer slightly modified vesicle structure and size, while it decreased the vesicle deformability. Caffeic acid diffusion coefficients from ethosome and ethosome gel were, respectively, 137- and 33-fold lower with respect to the aqueous solution. At last, the caffeic acid permeation and antioxidant power of ethosome were more intense with respect to the simple solution.
Dental caries is the most common disease in the human mouth. Streptococcus mutans is the primary cariogenic bacteria. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibit S. mutans growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases. However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria ( Streptococcus mutans , Streptococcus sobrinus , Actinomyces viscosus and Lactobacillus acidophilus ) and its effects on the biofilm-forming and cariogenic abilities of S. mutans . CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of S. mutans biofilms and its metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of S. mutans associated with cariogenicity, including acid production, acid tolerance and its ability to produce extracellular polysaccharides without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.
The present study aimed to prepare usnic acid (UA)-loaded chitosan (CS) nanoparticles (UA-CS NPs) and evaluate its antibacterial activity against biofilm-forming pathogenic bacteria. UA-CS NPs were prepared through simple ionic gelification of UA with CS, and further characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and field-emission transmission electron microscopy. The UA-CS NPs presented a loading capacity (LC) of 5.2%, encapsulation efficiency (EE) of 24%, and a spherical shape and rough surface. The maximum release of UA was higher in pH 1.2 buffer solution as compared to that in pH 6.8 and 7.4 buffer solution. The average size and zeta potential of the UA-CS NPs was 311.5 ± 49.9 nm in diameter and +27.3 ± 0.8 mV, respectively. The newly prepared UA-CS NPs exhibited antibacterial activity against persister cells obtained from the stationary phase in batch culture, mature biofilms, and antibiotic-induced gram-positive and gram-negative pathogenic bacteria. Exposure of sub-inhibitory concentrations of UA-CS NPs to the bacterial cells resulted in a change in morphology. The present study suggests an alternative method for the application of UA into nanoparticles. Furthermore, the anti-persister activity of UA-CS NPs may be another possible strategy for the treatment of infections caused by biofilm-forming pathogenic bacteria.
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.
Listeria monocytogenes, a human foodborne pathogen that causes listeriosis with high-rate mortality, has been reported to be resistant to commonly used antibiotics. New antibiotics or cocktails of existing antibiotics with synergistic compounds are in high demand for treating this multi-drug-resistant pathogen. Fosfomycin is one of the novel and promising therapeutic antibiotics for the treatment of listeriosis. However, some L. monocytogenes strains with the FosX gene were recently reported to survive from the fosfomycin treatment. This work aims to identify FosX inhibitors that can revive fosfomycin in treating resistant L. monocytogenes. Since structures and activities of the FosX protein in L. monocytogenes have been well studied, we used an integrated computational and experimental approach to identify FosX inhibitors that show synergistic effect with fosfomycin in treating resistant L. monocytogenes. Specifically, automated ligand docking was implemented to perform virtual screening of the Indofine natural-product database and FDA-approved drugs to identify potential inhibitors. An in vitro bacterial growth inhibition test was then utilized to verify the effectiveness of identified compounds combined with fosfomycin in inhibiting the resistant L. monocytogenes strains. Two phenolic acids, i.e., caffeic acid and chlorogenic acid, were predicted as high-affinity FosX inhibitors from the ligand-docking platform. Experiments with these compounds indicated that the cocktail of either caffeic acid (1.5 mg/mL) or chlorogenic acid (3 mg/mL) with fosfomycin (50 mg/L) was able to significantly inhibit the growth of the pathogen. The finding of this work implies that the combination of fosfomycin with either caffeic acid or chlorogenic acid is of potential to be used in the clinical treatment of Listeria infections.
Anthropic activity in Antarctica has been increasing considerably in recent years, which could have an important impact on the local microbiota affecting multiple features, including the bacterial resistome. As such, our study focused on determining the antibiotic-resistance patterns and antibiotic-resistance genes of bacteria recovered from freshwater samples collected in areas of Antarctica under different degrees of human influence. Aerobic heterotrophic bacteria were subjected to antibiotic susceptibility testing and PCR. The isolates collected from regions of high human intervention were resistant to several antibiotic groups, and were mainly associated with the presence of genes encoding aminoglycosides-modifying enzymes (AMEs) and extended-spectrum β-lactamases (ESBLs). Moreover, these isolates were resistant to synthetic and semi-synthetic drugs, in contrast with those recovered from zones with low human intervention, which resulted highly susceptible to antibiotics. On the other hand, we observed that zone A, under human influence, presented a higher richness and diversity of antibiotic-resistance genes (ARGs) in comparison with zones B and C, which have low human activity. Our results suggest that human activity has an impact on the local microbiota, in which strains recovered from zones under anthropic influence were considerably more resistant than those collected from remote regions.
Developing a novel agent and understanding the interaction model between multipolymer nanoparticles and bacteria could be worthwhile to induce the protection of crops with the prevalence of frequent hazards because of the use of pesticides and chemical resistance. Unlike metal nanoparticles, multipolymer nanoparticles have bacteriostatic properties against Ralstonia solanacearum that can trigger bacterial wilt by infecting the plant. Therefore, a novel poly(lactic-co-glycolic acid) nanoparticle containing caffeic acid phenethyl ester (CAPE) and methyl caffeate (MC) was prepared with the sustained-release property (for 10 d at pH 6.5); here, 50% of the cumulative release rate was achieved. It was observed that the cytomembrane of R. solanacearum was jeopardized by the nanoparticle by the creation of large holes on the bacterial surface. The nanoparticle has an approximate EC50 value of 0.285 mg mL⁻¹ with active pharmaceutical ingredients (APIs), while the drug dosage could be reduced by 2/3. Furthermore, to reveal the possible mechanism of interaction between the multipolymer nanoparticles and bacteria, a formidable inhibition effect was observed; the pathogenicity-related genes, namely, phcA, phcB, pehC, egl, pilT, and polA, of R. solanacearum were downregulated by 1/2, 1/42, 1/13, 1/6, 1/2, and 1/8, respectively, showing significant effects on the major virulence-related genes. Hence, a novel nanoparticle with excellent antibacterial and sustained-release properties has been prepared, possessing the potential to replace chemical pesticides and serve as a new control strategy for mulberry blight disease.
Aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria. The mechanism of bactericidal action by aminoglycosides is well-known, by which it terminates the cytoplasmic protein synthesis. However, the potentials of aminoglycosides become hindered when facing the evolution of bacterial resistance mechanisms. Among multiple resistance mechanisms displayed by bacteria against antibiotics, the formation of biofilm is the mechanism that provides a barrier for antibiotics to reach the cellular level. Bacteria present in the biofilm also get protection against the impact of host immune responses, harsh environmental conditions, and other antimicrobial treatments. Hence, with the multifaceted resistance developed by biofilm-forming pathogenic bacteria, antibiotics are therefore discontinued for further applications. However, the recent research developed several alternative strategies such as optimization of the active concentration, modification of the environmental conditions, modification of the chemical structure, combinatorial application with other active agents, and formulation with biocompatible carrier materials to revitalize and exploit the new potential of aminoglycosides. The present review article describes the above mentioned multiple approaches and possible mechanisms for the application of aminoglycosides to treat biofilm-associated infections.
The sol–gel route represents a valuable technique to obtain functional materials, in which organic and inorganic members are closely connected. Herein, four hybrid materials, containing caffeic acid entrapped in a silica matrix at 5, 10, 15, and 20 wt.%, were synthesized and characterized through Fourier-Transform Infrared (FT-IR) and Ultraviolet-Visible (UV–Vis) spectroscopy. FT-IR analysis was also performed to evaluate the ability to induce the hydroxyapatite nucleation. Despite some structural changes occurring on the phenol molecular skeleton, hybrid materials showed scavenging properties vs. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) radical cation (ABTS•+), which was dependent on the tested dose and on the caffeic acid wt.%. The SiO2/caffeic acid materials are proposed as valuable antibacterial agents against Escherichia coli and Enterococcus faecalis.
As a natural polysaccharide, chitosan possesses good biocompatibility, biodegradability and biosafety. Its hydroxyl and amino groups make it an ideal carrier material in the construction of polymer-drug conjugates. In recent years, various synthetic strategies have been used to couple chitosan with active substances to obtain conjugates with diverse structures and unique functions. In particular, chitosan conjugates with antimicrobial activity have shown great application prospects in the fields of medicine, food, and agriculture in recent years. Hence, we will place substantial emphasis on the synthetic approaches for preparing chitosan conjugates and their antimicrobial applications, which are not well summarized. Meanwhile, the challenges, limitations, and prospects of antimicrobial chitosan conjugates are described and discussed.
American Foulbrood (AFB) is a deadly bacterial disease affecting pupal and larval honey bees. AFB is caused by the endospore-forming bacterium Paenibacillus larvae (PL). Propolis, which contains a variety of organic compounds, is a product of bee foraging and is a resinous substance derived from botanical substances found primarily in trees. Several compounds from the class of caffeic acid esters, which are commonly found in propolis, have been shown to have antibacterial activity against PL. In this study, six different caffeic acid esters were synthesized, purified, spectroscopically analyzed, and tested for their activity against PL to determine the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Caffeic acid isopropenyl ester (CAIE), caffeic acid benzyl ester (CABE), and caffeic acid phenethyl ester (CAPE) were the most effective in inhibiting PL growth and killing PL cell with MICs and MBCs of 125 µg/mL when used individually, and a MIC and MBC of 31.25 µg/mL for each compound alone when CAIE, CABE, and CAPE are used in combination against PL. These compounds inhibited bacterial growth through a bactericidal effect, which revealed cell killing but no lysis of PL cells after 18 h. Incubation with CAIE, CABE, and CAPE at their MICs significantly increased reactive oxygen species levels and significantly changed glutathione levels within PL cells. Caffeic acid esters are potent bactericidal compounds against PL and eliminate bacterial growth through an oxidative stress mechanism.
Titanium implants are extensively used in biomedical applications due to their excellent biocompatibility, corrosion resistance, and superb mechanical stability. In this work, we present the use of polycaffeic acid (PCA) to immobilize metallic silver on the surface of titanium materials to prevent implant bacterial infection. Caffeic acid is a plant-derived phenolic compound, rich in catechol moieties and it can form functional coatings using alkaline buffers and with UV irradiation. This combination can trigger oxidative polymerization and deposition on the surface of metallic substrates. Using PCA can also give advantages in bone implants in decreasing inflammation by decelerating macrophage and osteoclast activity. Here, chemical and physical properties were investigated using FE-SEM, EDS, XPS, AFM, and contact angle. The in vitro biocompatibility and antibacterial studies show that PCA with metallic silver can inhibit bacterial growth, and proliferation of MC-3T3 cells was observed. Therefore, our results suggest that the introduced approach can be considered as a potential method for functional implant coating application in the orthopedic field.
Caffeic acid (CA) is a phenolic compound synthesized by all plant species and is present in foods such as coffee, wine, tea, and popular medicines such as propolis. This phenolic acid and its derivatives have antioxidant, anti-inflammatory and anticarcinogenic activity.
In vitro and in vivo studies have demonstrated the anticarcinogenic activity of this compound against an important type of cancer, hepatocarcinoma (HCC), considered to be of high incidence, highly aggressive and causing considerable mortality across the
world. The anticancer properties of CA are associated with its antioxidant and pro-oxidant capacity, attributed to its chemical structure that has free phenolic hydroxyls, the number
and position of OH in the catechol group and the double bond in the carbonic chain. Pharmacokinetic studies indicate that this compound is hydrolyzed by the microflora of colonies and metabolized mainly in the intestinal mucosa through phase II enzymes,
submitted to conjugation and methylation processes, forming sulphated, glucuronic and/or methylated conjugates by the action of sulfotransferases, UDP-glucotransferases, and o-methyltransferases, respectively. The transmembrane flux of CA in intestinal cells
occurs through active transport mediated by monocarboxylic acid carriers. CA can act by preventing the production of ROS (reactive oxygen species), inducing DNA oxidation of cancer cells, as well as reducing tumor cell angiogenesis, blocking STATS (transcription factor and signal translation 3) and suppression of MMP2 and MMP-9
(collagen IV metalloproteases). Thus, this review provides an overview of the chemical and pharmacological parameters of CA and its derivatives, demonstrating its mechanism of action and pharmacokinetic aspects, as well as a critical analysis of its action in the fight against hepatocarcinoma
Chitosan-based nanomaterials have attracted significant attention in the biomedical field because of their unique biodegradable, biocompatible, non-toxic, and antimicrobial nature. Multiple perspectives of the proposed antibacterial effect and mode of action of chitosan-based nanomaterials are reviewed. Chitosan is presented as an ideal biomaterial for antimicrobial wound dressings that can either be fabricated alone in its native form or upgraded and incorporated with antibiotics, metallic antimicrobial particles, natural compounds and extracts in order to increase the antimicrobial effect. Since chitosan and its derivatives can enhance drug permeability across the blood-brain barrier, they can be also used as effective brain drug delivery carriers. Some of the recent chitosan formulations for brain uptake of various drugs are presented. The use of chitosan and its derivatives in other biomedical applications is also briefly discussed.
Background:
Plants have always played important role in treating human and animal diseases as a therapeutic agent for traditional medicine. Through extensive research throughout the world, potential of natural products have been identified to control the over activity of many enzymes. In-silico screening a library of chlorogenic acid derivatives highlighted some novel compounds which were found effective against urease enzyme and cancer causing H. Pylori bacterium. Selected top ligands possessing minimum binding energy and good docking score were synthesized in wet lab by suitable procedure and evaluated for urease enzyme inhibition and free radical scavenging property. Synthetic scheme includes three step reactions i. e protection of hydroxyl group of quinic acid part of chlorogenic acid with lactonisation process, anilide formation by reaction with substituted anilines followed by extraction with ethyl acetate under vacuum and deprotection of hydroxyl groups by treatment with hydrochloric acid.
Results:
In-vitro results of the series concluded that compounds C4a, C4d and C4b (IC50 11.01 ± 0.013, 13.8 ± 0.041 and 15.86 ± 0.004 µM respectively in urease inhibition and 5.10 ± 0.018, 5.34 ± 0.007 and 6.01 ± 0.005 µM in antioxidant property against DPPH) were found to be significantly potent with excellent dock score - 10.091, - 10.603, - 9.833 and binding energy - 62.674, - 63.352, 56.267 kg/mol as compared to standard drugs thiourea and acetohydroxamic acid (- 3.459, - 3.049 and - 21.156 kJ/mol and - 17.454 kJ/mol) whereas compounds C4c, C4(e, h) exhibited moderate in vivo activity when compared to standard.
Conclusions:
Selected candidates from the outcome of in vitro urease inhibitory were further examined for anti-H. Pylori activity by well diffusion method against H. pylori bacterium (DSM 4867). Compound C4a showed significant anti-H. Pylori activity with zone of inhibition 10.00 ± 0.00 mm and MIC value 500 μg/mL as compared to standard drug acetohydroxamic acid having zone of inhibition 9.00 ± 0.50 mm and MIC 1000 μg/mL. Molecular docking studies also showed that compounds show strong inhibition by forming strong hydrogen bonding interactions with residues of pocket site in target protein. Hence, the present investigation studies will provide a new vision for the discovery of potent agents against H. Pylori and urease associated diseases.
The present study evaluates the antibacterial effects of a set of 16 synthesized caffeic acid ester derivatives against strains of Staphylococcus aureus and Escherichia coli , as well as discusses their structure-activity relationship (SAR). The antibacterial assays were performed using microdilution techniques in 96-well microplates to determine minimal inhibitory concentration (MIC). The results revealed that five of the compounds present strong to optimum antibacterial effect. Of the sixteen ester derivatives evaluated, the products with alkyl side chains, as propyl caffeate ( 3 ), butyl caffeate ( 6 ), and pentyl caffeate ( 7 ), presented the best antibacterial activity with MIC values of around 0.20 μ M against Escherichia coli and only butyl caffeate ( 6 ) showing the same MIC against Staphylococcus aureus . For products with aryl substituents, the best MIC results against the tested strain of Escherichia coli were 0.23 µ M for (di-(4-chlorobenzyl)) caffeate ( 13 ) and 0.29 µ M for diphenylmethyl caffeate ( 10 ) and all were less active against the Staphylococcus aureus strain. Preliminary quantitative structure-activity relationship (QSAR) analyses confirmed that certain structural characteristics, such as a median linear carbon chain and the presence of electron withdrawal substituents at the para position of the aromatic ring, help potentiate antibacterial activity.
Dental caries is multifactorial disease and an important health problem worldwide. Streptococcus mutans is considered as a major cariogenic agent in oral cavity. This bacteria can synthetize soluble and insoluble glucans from sucrose by glucosyltransferases enzymes and generate stable biofilm on the tooth surface. Biological properties of Chilean propolis have been described and it includes antimicrobial, antifungal and antibiofilm activities. The main goal of this study was to quantify the concentrations of main flavonoids presents in Chilean propolis and compare some biological properties such as antimicrobial and antibiofilm activity of individual compounds and the mixture of this compounds, against S. mutans cultures. Chilean propolis was studied and some polyphenols presents in this extract was quantified by HPLC-DAD using commercial standards of apigenin, quercetin, pinocembrin and caffeic acid phenethyl ester (CAPE). MIC for antimicrobial activity was determined by serial dilution method and biofilm thickness on S. mutans was quantified by confocal microscopy. Pinocembrin, apigenin, quercetin and caffeic acid phenethyl ester (CAPE) are the most abundant compounds in Chilean propolis. These polyphenols have strong antimicrobial and antibiofilm potential at low concentrations. However, pinocembrin and apigenin have a greater contribution for this action. The effect of polyphenols on S. mutans is produced by a combination of mechanisms to decrease bacterial growth and affect biofilm proliferation due to changes in their architecture.
Hypoxia inducible factor and nuclear factor-kappa beta pathways have been proposed as therapeutic targets for several inflammatory diseases. Caffeic acid phenethyl ester (CAPE) and piceatannol (PIC) are natural anti-inflammatory compounds; however, poor bioavailability and limited understanding of biomolecular mechanistic limits its clinical use. The aims of this study are to enhance bioavailability and investigate their impact on nuclear p65 and HIF-1α for the first time in experimental colitis.
Dextran sulphate sodium was used to induce colitis in mice and effect of either free CAPE/PIC or CAPE/PIC loaded albumin nanoparticles treatment was observed on disease development and levels of cellular p65 and HIF-1α.
Our results indicate that albumin nano-encapsulation of CAPE/PIC not only enhances its anti-inflammatory potential but also potentiates its ability to effectively modulate inflammation related biomolecular pathways. Hence, combining nanotechnology with natural compounds could result in development of new therapeutic options for IBD.
Electronic supplementary material
The online version of this article (10.1007/s13346-018-00597-9) contains supplementary material, which is available to authorized users.
In the present study, the antibacterial potential of chitosan grafted with phenolics (CPCs) such as caffeic acid (CCA), ferulic
(CFA), and sinapic acid (CSA) were evaluated against foodborne pathogens like Pseudomonas aeruginosa (PA) and Listeria
monocytogenes (LM). The geometric means of minimum inhibitory concentration (MIC range 0.05–0.33 mg/ml), bactericidal
concentration (MBC range 0.30–0.45 mg/ml), biofilm inhibitory concentration (BIC range 0.42–0.83 mg/ml), and biofilm
eradication concentration (BEC range 1.71–3.70 mg/ml) of CPCs were found to be lower than the MIC (0.12–1.08 mg/ml),
MBC (0.17–1.84 mg/ml), BIC (4.0–4.50 mg/ml), and BEC (17.4–23.0 mg/ml) of unmodified chitosan against PA and LM.
CPCs attenuated the biofilms of PA and LM by increasing the membrane permeability of bacteria embedded within the
biofilms. Further, sub MIC of CPCs (0.5×MIC) significantly reduced the biofilm adhesion (p<0.001) by representative
strains of LM (CCA: 72.2±3.5, CFA: 79.3±0.9, and CSA: 74.9±1.5%) and PA (CCA: 64±1.1, CFA: 67.8±0.8, and CSA:
65.7±4.9%). These results suggested the antibacterial and anti-biofilm potential of CPCs that can be exploited to control
foodborne pathogenic infections.
Biofilm formation by Staphylococcus aureus on food contact surfaces is one of the most important issues for the food safety. The difficulties in controlling biofilms have driven the search for new antibacterial and antibiofilm agents from natural resources. The aims of the present study were to investigate the antibacterial and antibiofilm activities of the methanolic extract from Zanthoxylum bungeanum Maxim. leaves and identify the active compounds. By bioassay guide of inhibitory activity against S. aureus, four antibacterial compounds were separated from this extract and identified as neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and 4-O-caffeoyl-2,3-dihydroxy-2-C-methylbutyric acid based on MS and NMR data analyses. The four compounds exhibited moderate antibacterial activity against S. aureus with minimum inhibitory concentration of 5 mg/mL. Moreover, a fraction consisted of the four compounds was subjected to antibiofilm assays against S. aureus. Crystal violet staining and XTT reduction assay demonstrated that this fraction showed an excellent inhibitory efficacy on the biomass and metabolic activity of S. aureus biofilm. Scanning electron microscopic observation displayed that this fraction induced severe morphological changes in the architecture of S. aureus biofilm, which further confirmed that it possessed a potent inhibitory activity on the biofilm formation of S. aureus. So, these results suggested that Z. bungeanum leaves could be used as an attractive and promising candidate for the development of natural antibacterial agent for controlling food-related bacterial biofilms.
Healthcare-associated infections have increasingly become problematic in the endoscopic procedures resulting in several severe diseases such as carbapenem-resistant Enterobacteriaceae (CRE)-related infections, pneumonia, and bacteremia. Especially, some bacterial strains are resistant to traditional antimicrobials. Therefore, the necessity of developing new antibiotics or management to deal with bacterial infections has been increasing. The current study combined a low concentration of glutaraldehyde (GTA) with near-infrared (NIR) light and 405-nm laser to entail antibacterial activity on Staphylococcus aureus biofilm. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony forming unit (CFU) counting were used to quantify the viable cells while fluorescent and scanning electron microscopic images were used to qualitatively evaluate the cell membrane integrity and structural deformation, respectively. Practically, S. aureus biofilm was highly susceptible (7% cell viability and 6.8-log CFU/cm² bacterial reduction for MTT assay and CFU analysis, respectively) to the combination of GTA (0.1%), NIR light (270 J/cm²), and 405-nm laser (288 J/cm²) exposure. GTA could form either DNA-protein or protein-protein crosslinks to inhibit DNA and protein synthesis. The NIR light induced the thermal damage on protein/enzymes while 405-nm laser could induce reactive oxygen species (ROS) to damage the bacterial membrane. Thus, the proposed technique may be a feasible modality for endoscope cleaning to prevent any secondary infection in the healthcare industry.
The relentless rise of antibiotic resistance is considered one of the most serious problems facing mankind. This mini-review will cover three cutting-edge approaches that use light-based techniques to kill antibiotic-resistant microbial species, and treat localized infections. First, we will discuss antimicrobial photodynamic inactivation using rationally designed photosensitizes combined with visible light, with the added possibility of strong potentiation by inorganic salts such as potassium iodide. Second, the use of blue and violet light alone that activates endogenous photoactive porphyrins within the microbial cells. Third, it is used for "safe UVC" at wavelengths between 200 nm and 230 nm that can kill microbial cells without damaging host mammalian cells. We have gained evidence that all these approaches can kill multidrug resistant bacteria in vitro, and they do not induce themselves any resistance, and moreover can treat animal models of localized infections caused by resistant species that can be monitored by noninvasive bioluminescence imaging. Light-based antimicrobial approaches are becoming a growing translational part of anti-infective treatments in the current age of resistance.
Phenolic compounds constitute one of the most promising and ubiquitous groups with many biological activities. Synergistic interactions between natural phenolic compounds and antibiotics could offer a desired alternative approach to the therapies against multidrug-resistant bacteria. The objective of the presented study was to assess the antibacterial potential of caffeic acid (CA) alone and in antibiotic-phytochemical combination against Staphylococcus aureus reference and clinical strains isolated from infected wounds. The caffeic acid tested in the presented study showed diverse effects on S. aureus strains with the minimum inhibitory concentration (MIC) varied from 256 μ g/mL to 1024 μ g/mL. The supplementation of Mueller-Hinton agar (MHA) with 1/4 MIC of CA resulted in augmented antibacterial effect of erythromycin, clindamycin, and cefoxitin and to the lesser extent of vancomycin. The observed antimicrobial action of CA seemed to be rather strain than antibiotic dependent. Our data support the notion that CA alone exerts antibacterial activity against S. aureus clinical strains and has capacity to potentiate antimicrobial effect in combination with antibiotics. The synergy between CA and antibiotics demonstrates its potential as a novel antibacterial tool which could improve the treatment of intractable infections caused by multidrug-resistant strains.
Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent. In order to examine the anti-HBV effects of rosmarinic acid, HBV-infected primary human hepatocytes from a humanized mouse liver were treated with rosmarinic acid. The rosmarinic acid treatment decreased HBV components including the amounts of extracellular HBV DNA with negligible cytotoxicity. We also investigated the combined effects of rosmarinic acid and the NA, lamivudine. rosmarinic acid slightly enhanced the anti-HBV activity of lamivudine, suggesting that the HBV replication step targeted by rosmarinic acid is distinct from that of NA. We analyzed an additional 25 rosmarinic acid derivatives, and found that 5 also inhibited ε-Pol. Structural comparisons between these derivatives implied that the “two phenolic hydroxyl groups at both ends” and the “caffeic acid-like structure” of rosmarinic acid are critical for the inhibition of ε-Pol binding. Collectively, our results demonstrate that rosmarinic acid inhibits HBV replication in HBV-infected cells by specifically targeting ε-Pol binding.
Fungal pathogens are a growing threat to public health. As human immunodeficiency becomes increasingly common, fungal infections are becoming more prevalent. The use of antifungal agents for prophylaxis and treatment of fungal infections has favored the emergence of previously rare or unidentified species of drug‐resistant fungal pathogens, including several Candida and Cryptococcus species, as well as mold pathogens. As these new and increasingly drug‐resistant fungal pathogens continue to emerge, novel strategies for rapid identification and treatment are necessary to combat these life‐threatening infections.
Acinetobacter baumannii is a Gram-negative, aerobic, non-motile, and pleomorphic bacillus. A. baumanii is also a highly-infectious pathogen causing high mortality and morbidity rates in intensive care units. The discovery of novel agents against A. baumanii infections is urgently needed due to the emergence of drug-resistant A. baumannii strains and the limited number of efficacious antibiotics available for treatment. In addition to the production of several virulence factors, A. baumannii forms biofilms on the host cell surface as well. Formation of biofilms occurs through initial surface attachment, microcolony formation, biofilm maturation, and detachment stages, and is one of the major drug resistance mechanisms employed by A. baumanii. Several studies have previously reported the efficacy of naturally-derived and synthetic compounds as anti-biofilm and anti-virulence agents against A. baumannii. Here, inhibition of biofilm formation and virulence factors of A. baumannii using naturally-derived and synthetic compounds are reviewed.
Persister cells are transiently antibiotic-tolerant and dormant subpopulations that are produced to escape the effects of antibiotics within biofilms or planktonic cell populations. Persister cells are of high clinical importance due to their tolerance to antimicrobial agents and subsequent failure in antibiotic treatments. Understanding persister cell formation mechanisms is therefore highly important for developing effective therapeutic strategies against pathogenic bacterial persisters. Several anti-persister compounds have been previously identified via isolation from natural resources or chemical synthesis. Furthermore, a combination of these compounds with antibiotics or non-antibiotic drugs also allows action on multiple targets while reducing the administration frequency. Here, we present a comprehensive overview of the clinical importance and formation mechanisms of persister cells as well as the current treatment strategies against persister cell formations in chronic infections.
Background:
SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic.
Purpose:
This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation.
Methods:
A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions.
Results: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. Conclusion:
This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models
Caffeic acid (CA) is a polyphenol widely distributed in the plant kingdom. Studies have shown CA possesses antithrombotic activity in mouse cerebral arterioles in vivo and inhibits platelet aggregation in vitro. However, little is known regarding the effects of CA on platelet-mediated clot retraction. We investigated the effects of CA on platelet activation and clot retraction in response to thrombin. CA inhibited thrombin-induced platelet aggregation, calcium mobilization, adenosine 1,4,5-tri-phosphate (ATP) release, P-selectin expression and fibrinogen binding to integrin αIIbβ3 activation without inducing any cytotoxic effect, and inhibited the phosphorylations of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) in thrombin-stimulated platelets. In addition, CA enhanced cyclic adenosine monophosphate (cAMP) generation, which led to the phosphorylations of vasodilator-stimulated phosphoprotein (VASP) and inositol trisphosphate (IP3) receptor, and reduced clot retraction without any anticoagulation effect. Dipyridamole, a phosphodiesterase 3 (PDE3) inhibitor, reduced clot retraction, which suggested CA-mediated cAMP generation is the main signaling pathway responsible for its inhibition of clot retraction. Taken together, the findings of the present study suggest that CA may have potential as a therapeutic for the prevention of thrombotic disorders.
The phytochemical study of the aerial part of Mesona chinensis led to the isolation of five new caffeic acid oligomers (1–5), as well as four known analogues (6–9). The structures of the new compounds including their absolute configurations were elucidated by comprehensive spectroscopic analysis, chemical method, and quantum-chemical electronic circular dichroism (ECD) calculation. Among the isolates, compound 7 showed significant in vitro antiviral activity on respiratory syncytial virus (RSV).
Nanoparticles have emerged as an important carrier system to treat wounds as they permit the topical administration of an antimicrobial drug in a sustained and effective manner. On the other hand, if active excipients are added during the formulation, such as chitosan or graphene oxide, the developed nanoformulation could significantly improve its potential for chronic wound healing. Given that, we have conceived the fabrication and evaluation of rosmarinic acid loaded chitosan encapsulated graphene nanoparticles (RA-CH-G-NPOs) formulation to enhance wound healing capacity. The prepared nanoparticles were characterized by particle size, Zeta potential, FT-IR, SEM, TEM and AFM. It was observed the average diameter of RA-CH-G-NPOS is around 417.5 ± 18.3nm and showed sustained release behavior. Optimized RA-CH-G-NPOs were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro release, texture analysis, and viscosity. The antibacterial activity of optimized formulation was examined as a minimum inhibitory concentration against Staphylococcus aureus. The fabricated RA-CH-G-NPOs were than evaluated for in vitro antimicrobial activity by microdilution assay The combination of RA, Chitosan and Graphene oxide (GO) showed higher antibacterial activity of 0.0038 ± 0.2 mg/ml. Further, these nanoparticles were evaluated in- vivo for wound healing efficacy in Sprague Dawley rats. Histopathological evaluations demonstrated that RA-CH-G-NPOs showed significantly enhanced wound contraction, enhanced cell adhesion, epithelial migration, and high hydroxyproline content leading to faster and more efficient collagen synthesis as compared to plain carbopol, plain RA and controls. Hence the topical administration of fabricated RA-CH-G-NPOs appears to be an interesting and suitable strategy for the treatment of chronic wounds.
Chitosan and its derivatives can be called environmental purification functional materials as they can effectively control the growth and reproduction of hazardous bacteria and also control toxic pollutants. From the basic science to the latest developments and innovations, starting with the history of the material, this chapter presents a facile way to understand the antibacterial activity of the chitosan, together with other materials, to the reader. This chapter also summarizes the general developments in the study of antimicrobial applications. In the light of the current situation of the research and the progress in the related fields, this chapter discusses the differences among influencing factors in detail and compares the antimicrobial activity between different physical states of chitosan. Also, this chaper discusses the more recent processes and applications.
In this study, chitosan (CS) was grafted with phenolic acids including gallic acid (GA-g-CS) and caffeic acid (CA-g-CS) through carbodiimide coupling. The conjugates were further developed into films by casting and were characterized in terms of appearance, structure, and mechanical and barrier properties, as well as antioxidant and antimicrobial activities; the purpose was to evaluate their potential application in food packaging. The results showed that the CA-g-CS film exhibited the highest tensile strength (10.67 ± 0.47 MPa) and elongation at break and had desirable barrier properties against water vapour (0.70 ± 0.02 g mm/m²h kPa) and oxygen (37.72 ± 0.23 meq/kg). In addition, both the GA-g-CS and CA-g-CS films displayed higher antioxidant activity than the CS films, while CA-g-CS also exhibited a significantly stronger (p < 0.05) inhibitory effect on Bacillus subtilis (G⁺) and Staphylococcus aureus (G⁺). These findings will contribute to a theoretical basis for the development of the CA-g-CS film into food packaging.
Biofilm formed by several pathogenic bacteria results in the development of resistance against antimicrobial compounds. The polymeric materials present in the biofilm architecture hinder the entry of antimicrobial compounds through the surface of bacterial cells which are embedded as well as enclosed beneath the biofilm matrix. Recent and past studies explored the alternative approaches to inhibit the formation of biofilm by different agents isolated from plants, animals, and microbes. Among these agents, chitosan and its derivatives have got more attention due to their properties such as biodegradability, biocompatibility, non-allergenic and non-toxicity. Recent researches have focused on employing chitosan and its derivatives as effective agents to inhibit biofilm formation and attenuate virulence properties by various pathogenic bacteria. Such antibiofilm activity of chitosan and its derivatives can be further enhanced by conjugation with a wide range of bioactive compounds. The present review describes the antibiofilm properties of chitosan and its derivatives against the pathogenic bacteria. This review also summarizes the mechanisms of biofilm inhibition exhibited by these molecules. The knowledge of the antibiofilm activities of chitosan and its derivatives as well as their underlying mechanisms provides essential insights for widening their applications in the future.
Four phenolic acid-grafted-chitosan conjugates were prepared with different phenolic acids including gallic acid (GLA), caffeic acid (CA), gentisate acid (GTA) and sinapic acid (SA), and their characteristics were analyzed. Furthermore, the antioxidant and antimicrobial activities of conjugates were compared to screen out the optimal conjugates. The characterization analysis showed that the UV absorption peaks of CA-g-CS were stronger than that of GLA-g-CS, indicating a higher substitution degree. In addition, the substitution degree and antioxidant activity of caffeic acid-grafted-chitosan (CA-g-CS) and gallic acid-grafted-chitosan (GLA-g-CS) had significantly (p < 0.05) higher than CS and other two conjugates. However, CA-g-CS demonstrated stronger bacteriostatic ability, of which the minimum inhibitory concentrations (MICs) against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis and Staphylococcus aureus were lower, and the inhibitory zones were larger than GLA-g-CS. In summary, the present findings will provide a theoretical basis for the expanding of CS application in food processing and preservation.
The uses of medicinal plants for combating various human ailments, food utility and additive purposes have been adapted from ancient routine custom. Currently, developing countries used plants as a major source of primary health care. Besides, the astonishing increments of emerging drug resistance pathogenic microbes encourage the utilization of medicinal plants as preeminent alternative sources of new bioactive substances. Extensive research findings are reported in the last three decades, but most of them are checklist way of findings. Methods to investigate the phytoconstituents and their biological effects are limited. This review contains brief explanations of the method of selecting medicinal plants, ways of getting the crude as well as essential oil extracts, phytochemical screening, and in-vitro evaluation of antimicrobial activity. Furthermore, the potent medicinal plants reported with respective solvent fractionated and non-fractionated plant extracts used for in-vitro analysis are also described as a glance. The prioritized medicinal plant's bioactive substances molecular structure and biological effects are revealed in the content.
In this work, the novel Spiro cycles with high potential antibacterial activity were synthesized via a one-pot and environmentally friendly electrochemical approach, without toxic reagents and solvents. In the first, electrochemical oxidation of caffeic acid (1) in the presence of barbituric acids (3a-c) as nucleophiles have been studied using cyclic voltammetry and controlled-potential coulometry. The obtained electrochemical results demonstrate that an electrooxidative/Michael-type sequential reaction occurs between the barbituric acids and the caffeic acid o-quinone produced by electrooxidation of caffeic acid leading to the corresponding novel Spiro cycles (8a-c). The mechanism of the electrochemical reaction was suggested as an ECEC (Electron transfer, Chemical reaction, Electron transfer, Chemical reaction) pathway using cyclic voltammetry, controlled-potential coulometry and spectroscopic data. The antibacterial activities of the synthesized compounds were investigated and compared with caffeic acid and barbituric acids.
Background:
Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT).
Objectives:
To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia.
Methods:
This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables.
Results:
Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03).
Conclusions:
CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.
New organic-inorganic hybrid materials were synthesized by an acid catalysed sol-gel approach, using silicon alkoxide and low molecular weight polyethylene glycol (PEG400) as inorganic and organic precursor, respectively. Chlorogenic acid (CGA), an antioxidant natural phenol compound, enriched further the organic component. Hybrids synthesized, all identical in terms of their starting materials, but differing in terms of their relative proportions, were characterized by means of Fourier Transform InfraRed (FTIR) measurements, UV–Vis spectroscopy, and UHPLC-HRMS analysis. The preservation of the intrinsic chlorogenic acid ability to scavenge, in a dose-dependent manner, radical species was investigated by directly exposing the hybrids to DPPH radical and ABTS radical cation. The relative ratio of both the natural compound and PEG heavily affected the antiradical response, suggesting that chemical interactions in the established network were able, based on components’ ratio, to differently mask and/or display the CGA moieties, commonly deemed relevant for antioxidant power exerting. Cell culture MTT assay was used to assess the biocompatibility of hybrid materials towards fibroblast NIH-3 T3 cells and neuroblastoma SH-SY5Y cells. Cells tested appeared differently responsive. In particular, a marked cell viability increase was observed when hybrids with low PEG amount (6%) and high CGA (15%) were directly exposed to fibroblast cells, whose mitochondrial redox activity was negatively affected by hybrid synthesized using the highest organic component rate (both PEG and CGA). Cell viability and morphology of human neuroblastoma SH-SY5Y cells were broadly compromised regardless of organic/inorganic starting materials ratio, suggesting the ability of hybrids to exert pro-oxidant effect towards tumour cells and to selectively interfere with their growth. The hybrids, able to elicit cleverly anti- or proliferative effects, were also shown to be bioactive. In fact, a biologically active hydroxyapatite layer was observed to be formed on the surface of the smart synthesized materials. This feature, which makes them a valuable bonding interface with tissues, opens new scenario aiming at further investigating the employment of natural phenol compounds in versatile sol–gel synthesis routes.
Antimicrobial resistance threatens a resurgence of life-threatening bacterial infections and the potential demise of many aspects of modern medicine. Despite intensive drug discovery efforts, no new classes of antibiotics have been developed into new medicines for decades, in large part owing to the stringent chemical, biological and pharmacological requisites for effective antibiotic drugs. Combinations of antibiotics and of antibiotics with non-antibiotic activity-enhancing compounds offer a productive strategy to address the widespread emergence of antibiotic-resistant strains. In this Review, we outline a theoretical and practical framework for the development of effective antibiotic combinations.
Caffeic acid phenethyl ester (CAPE) is a natural compound with anticancer activities but has low water solubility. In this work, sucrose fatty acid ester (SFAE) was used to nanoencapsulate CAPE in aqueous propylene glycol (PG) with a temperature-cycle method by heating at 90 °C for 20 min and cooling to 21 °C, followed by additional heating at 90 °C for 5 min and cooling to 21 °C. A higher amount of PG facilitated encapsulation with up to 0.1%w/w CAPE in 1.0% w/w SFAE. Additional 0.3%w/w thymol further improved the CAPE loading capability to 0.15%w/w to form nanoparticles smaller than 100 nm and stable in 30 days at 21 °C. Nanoencapsulation enhanced cytotoxicity of CAPE against colon cancer HCT-116 and breast cancer MCF-7 cells, and thymol additionally enhanced the cytotoxicity of CAPE dispersions. This work provides a new approach to nanoencapsulate CAPE in stable aqueous dispersions with improved cytotoxicity.
Organic compounds with a caffeoyl moiety (e.g. caffeic acid, rosmarinic acid, chicoric acid, etc.) have antiviral properties towards herpes simplex (HSV), influenza and immunodeficiency viruses (HIV). This study evaluated the HSV antiviral properties of caffeic acid when paired with a variety of metal and other inorganic ions. The results demonstrated that the antiviral activity of caffeic acid increased upwards of 100-fold by the addition of cations, such as Fe³⁺, and anionic molecules, such as molybdate and phosphate. Cellular toxicity tests of the caffeic acid chelates showed that they have low toxicities with selectivity indices (TD50/EC50) for Fe³⁺, MoO4²⁻, and PO4³⁻ chelates being 1700, >540, and >30, respectively. Caffeic acid paired with Fe³⁺ was tested against eight strains of viruses, including those from different families. The caffeic acid chelates were mostly effective against HSV1 and HSV2, but they also had moderate activity against vaccinia virus and a VSV-Ebola pseudotyped virus. All the viruses that were strongly impacted by the caffeic chelates require heparan sulfate proteoglycans for cellular attachment, so it is likely that caffeic chelates target and interfere with this mechanism. Since the caffeic acid chelates target an extra-cellular process, they might be able to be combined with existing medications, such as acyclovir, that target an intracellular process to achieve greater viral control.
Human enterovirus 71 (EV-A71) infections cause a wide array of diseases ranging from diarrhoea and rashes to hand-foot-and-mouth disease and, in rare cases, severe neurological disorders. No specific antiviral drug therapy is currently available. Extracts from seventy-five Chinese medicinal plants selected for antiviral activity based on the Chinese pharmacopeia and advice from traditional Chinese medicine clinicians were tested for activity against EV-A71. The aqueous extract of the rhizome of Cimicifuga heracleifolia (Sheng Ma) and Arnebia euchroma (Zi Cao) showed potent antiviral activity. The active fractions were isolated by bioassay-guided purification, and identified by a combination of high-resolution mass spectrometry and NMR. Fukinolic acid and cimicifugic acid A and J, were identified as active anti-EV-A71 compounds for Cimicifuga heracleifolia, whereas for Arnebia euchroma, two caffeic acid derivatives were tentatively deduced. Commercially available fukinolic acid analogues like L-chicoric acid and D-chicoric also showed in vitro micromolar activity against EV-A71 lab-strain and clinical isolates.
The antimicrobial efficacy of 400 nm photoirradiated caffeic acid (CA, 5 mM) was evaluated against Escherichia coli O157:H7 and Listeria innocua. A stronger antimicrobial effect was observed on E. coli than on L. innocua where the combined treatment resulted in 4 and 1 log(CFU/mL) reductions, respectively. The treatment's effects on cellular metabolism (resazurin assay), uptake of CA (fluorescence technique) and membrane damage (propidium iodide assay) were studied in both species. CA uptake increased in both species, but membrane damage was only observed in E. coli O157:H7. The treatment had minimal impact on metabolic activity in both species. The treatment applied to the surface of spinach leaves was found to be effective against E. coli O157:H7. The novel treatment proposed in this study has the potential to improve the microbial food safety of fresh produce.
Caffeic acid (CAF)has numerous health benefits mainly due to its antioxidant, antibacterial and fungicide properties. However, its incorporation in skin care products as anti-aging and the photoprotective agent is still limited due to its solubility and stability in oily matrices or solutions balanced with the skin pH. In this research, CAF–ethyl cellulose (EC) microparticles were produced by water-in-oil-water double emulsion solvent evaporation encapsulation technique using a biocompatible polymer, EC, as a coating material and a surfactant, polyvinyl alcohol, as a stabilizer of the double emulsion. The study assessed the influence of formulation parameters as the solubility of the polymer in organic solvents and the polymer concentration on microparticles final characteristics. CAF–EC microparticles were characterized by product yield, encapsulation efficiency, mean particle size, particle size distribution and polydispersity and imaged by scanning light microscopy. In vitro release profiles were obtained in water and octanol to mimic oily based and water-based matrices balanced with the skin pH. In vitro release kinetics studies were carried out to investigate the release pattern of CAF in simulated cosmetic formulations. Both the product yield and the encapsulation efficiency were found to be dependent on the solubility of the polymer in the organic phase. The product yield was mainly affected by operational factors such as the sticking and the agglomeration of the polymer to the walls and the magnet stirring during microparticles hardening and results from the encapsulation efficiency revealed that an increase of the polymer concentration led to an increase of the encapsulation efficiency. The usage of a water-soluble solvent contributed to a decrease in the mean particle size and reduction of polydispersity with higher polymer concentrations. The polymer concentration, the polymer solubility in the organic phase and the amount of CAF entrapped shown to affect the release in water, whereas the release in octanol was mainly independent of the amount of CAF entrapped in EC microparticles. The double emulsion solvent evaporation technique and the assessment of the selected formulation conditions have given significant and innovative insights on the microencapsulation of bioactive ingredients for cosmetics formulations.
Chitosan-phytochemical conjugates exhibited significant antibacterial effect with minimum inhibitory concentration (MIC) ranging from 128 to 2048 µg/ml against antibiotic-resistant fish pathogenic bacteria such as Edwardseilla tarda, Vibrio harveyi and Photobacterium damselaewhich were isolated from Korean cultured fish. Furthermore, the MIC values of old-fashioned antibiotics such as erythromycin and oxytertacycline drastically reduced in combination with chitosan-phytochemical conjugates against the fish pathogenic bacteria. The combination of conjugates with erythromycin and oxytetracycline gave median ∑FIC results ranging from 0.281 to 0.625 and 0.312 to 0.625, respectively. This result indicates the synergistic antibacterial effects and an increased susceptibility against the antibiotics.
In present study, the antigenotoxic activity of PLGA [poly (d, l-lactic-co-glycolic acid)] nanoparticles loaded with caffeic acid phenethyl ester (CAPE) was investigated in comparison with free CAPE using the AMES technique/Salmonella Microsome Assay. Additionally, to elucidate the impacts of the type of solvent effect on antigenotoxic activity, the following system were tested; CAPE in water (poor solvent), in ethyl alcohol (good solvent) and in PLGA nanoparticles (unknown). The effect of the nanoparticle system on solubility was investigated for the first time by assessing the antigenotoxic potential. In this study, the CAPE/PLGA nanoparticles (CAPE/PLGA NPs) were synthesized using an oil-in-water (o/w) single-emulsion solvent evaporation method with an average size of 206.2 ±1.2 nm, zeta potential of -19.8±2.5 mV, encapsulation efficiency of 87.2 ± 2.5% and drug loading of 53.3 ± 1.8 %. According to the results of antigenotoxic activity, the highest antimutagenic activity in both applied strains was found for CAPE in ethanol, and the lowest activity was detected for CAPE in water. Our study has shown that nanoparticle systems exhibit high antigenotoxic activity, which is similar to the results of CAPE dissolved in ethanol. These results have shown that nanoparticle systems increase biological activity of hydrophobic substances by increasing their solubility and that the use of PLGA instead of organic solvents in drug production may be provides an increase in theirs medical utility.
Hepatitis C virus (HCV) infection and its related liver disease have constituted a heavy burden worldwide. It had been reported that Drinking coffee could decrease mortality risk of HCV infected patients. Caffeic Acid (CA), the Coffee-related organic acid could inhibit HCV replication, however, the detailed mechanism of CA against HCV is unclear. In this study, we showed that CA could notably inhibit HCV replication. Mechanism study demonstrated that CA could induce HO-1 expression, which would trigger the IFNα antiviral response, and the antiviral effect of CA was attenuated when HO-1 activity was inhibited by SnPP (an HO-1 inhibitor). CA could also increase erythroid 2-related factor 2 (Nrf2) expression. When Nrf2 was knocked down by specific siRNA, HO-1 expression was concomitantly decreased while HCV expression was restored. Further study indicated that kelch-like ECH-associated protein 1 (Keap1) expression was decreased by CA in a p62/Sequestosome1 (p62)-dependent way, which would lead to the stabilization and accumulation of Nrf2. The decrease of Keap1 was restored when p62 was silenced by specific p62 siRNA, suggesting p62 was required for CA-mediated Keap1 downregulation. Taken together, the results demonstrated that CA could modulate Keap1/Nrf2 interaction via increasing p62 expression, which will lead to stabilization of Nrf2 and HO-1 induction and elicit IFNα antiviral response to suppress HCV replication.
