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Spectral analysis of H2O2 oxidation of ferrous HbS. Absorbance spectra were recorded before and after addition of 2 mm Na2S to 60 μm ferrous HbS and 60 μm ferrous HbS treated with 300 μm CA in the presence of 150 μm H2O2. Panel A shows the difference in the amount of sulfheme concentration in the presence and absence of CA. Panel B shows sulfheme concentration versus different H2O2 ratios to Hb. Error bars represent standard deviation.
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It is well documented that caffeic acid (3,4‐dihydroxycinnamic acid) (CA) interacts with and inhibits the oxidative reactions of myoglobin (Mb) and hemoglobin (Hb), and this interaction underlies its antioxidative action in meat. Sickle cell Hb (HbS) is known for its tendency to oxidize more readily than normal HbA in the presence of hydrogen perox...
Citations
... Ferulic acid has a variety of biological activities, especially in oxidative stress, inflammation, vascular endothelial injury, fibrosis, apoptosis and platelet aggregation [19]. Caffeic acid is a widely distributed hydroxycinnamic acid salt and phenylpropanoid metabolite in plant tissues, with multiple biological activities such as antioxidant, anti-cancer, antiviral, anti-inflammatory, and antidiabetic effects [19][20][21][22]. Syringic acid can inhibit the release of inflammatory mediators, alleviate inflammation, and possesses additional properties such as antioxidant [23,24]. ...
Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF, then the targets of them were obtained from TCMSP, ETCM, ITCM and Swiss TargetPrediction databases. RA disease related targets were obtained from DisGenet, OMIM and GeneCards databases. 99 overlapped targets were obtained using Venn diagram. The protein-protein interaction network (PPI)、the compound-target network (CT) and the compound-potential target genes-signaling pathways network (CPS) were built and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. And the core therapeutic targets were identified as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, RELA by network pharmacology analysis, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in mice model of xylene-induced ear edema and strong analgesic effect on acetic acid-induced withing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF could alleviate toe swelling and ameliorate joint damage. The elevation of serum content of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may exert regulation on the ERK and NF-κB pathway. The results provided a new perspective for the topical application of CF on RA.
... It also has multiple health benefits like anticancer, antidiabetic, antimutagenic, anti-atherosclerotic and cardioprotective effects [4,5]. CA possesses anti-sickling property that increases the oxygen binding affinity of human hemoglobin [6]. ...
... FerrylHb formation was followed by monitoring characteristic absorbance changes over time in the visible region (Kassa et al., 2017). In some cases, 1 mL of stored blood was incubated for 1 h at 37°C with various concentrations of caffeic acid or ascorbate (0.5 µM or 2.5 µM), known for their anti-ferryl activities (Dunne et al., 2006;Kassa et al., 2021). For the verification of the ferryl intermediate, 2 mM sodium sulfide (Na 2 S) was added to transform ferrylHb to sulfhemoglobin (sulfHb). ...
Red blood cells (RBCs) undergo metabolic, oxidative, and physiological changes during storage, collectively described as the “storage lesion.” The impact of storage on oxygen homeostasis, following transfusion, is not fully understood. We show that RBC storage induces changes in oxygen binding that were linked to changes in oxygen sensing (hypoxia-inducible factor, HIF-1α) mechanisms and mitochondrial respiration in human pulmonary arterial endothelial cells (HPAECs). A decrease in oxygen affinity (P50) to approximately 20 from 30 mmHg was seen at the first week but remained unchanged for up to 42 days. This led to the suppression of HIF-1α in the first 3 weeks due to limited oxygen supplies by RBCs. Furthermore, membrane oxidative damage, band 3 alterations, and subsequent microparticle (MP) formation were also noted. Mass spectrometric analysis revealed the upregulation of transitional endoplasmic reticulum ATPase, essential for clearing ROS-damaged membrane proteins and the protein DDI1 homolog, a proteasomal shuttle chaperone. Band 3 complex proteins and superoxide dismutase were among the downregulated proteins. Mitochondrial oxygen consumption rates measured in HPAECs incubated with RBC-derived MPs (14-day and 42-day) showed a rise in maximal respiration. Intervention strategies that target intracellular hemoglobin (Hb)’s redox transitions and membrane changes may lead to the reestablishment of oxygen homeostasis in old RBCs.
... Therefore, it is necessary to regulate the excessive autophagy activation and impaired autophagic flux through drug intervention to fight against common cardiovascular diseases (Abdellatif, Ljubojevic-Holzer, Madeo, & Sedej, 2020; C. . Notably, caffeic acid (3,4-dihydroxycinnamic acid) modified on the structure of cinnamic acid also has antioxidative (Kassa, Whalin, Richards, & Alayash, 2021), anti-inflammatory (Zielińska et al., 2021) and immunomodulatory effects (Tada et al., 2018). Recently, it was found that caffeic acid can regulate autophagy to improve diabetes nephropathy in rats (Matboli et al., 2017). ...
Background and Purpose: Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated. Experimental Approach: The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to H2O2. Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members. Key Results: Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased P-mTOR and increased LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10’s regulation on mTOR, leading to interrupted cardiac autophagic flux. Conclusions and Implications: Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury. Keywords: Myocardial ischemia-reperfusion; Cinnamamide derivatives; Autophagic flux; Sirt1; mTOR;
... 4-vinylguaiacol 4-ethenyl-2-methoxyphenol [1113][1114][1115] caffeic acid (E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid [669,748,[1116][1117][1118][1119][1120][1121][1122][1123][1124][1125][1126][1127][1128] isoferulic acid (E)-3-(3-hydroxy-4methoxyphenyl)prop-2enoic acid [1172][1173][1174][1175] paraxanthine 1,7-dimethyl-3H-purine-2,6-dione [1176] p-coumaric acid (E)-3-(4-hydroxyphenyl)prop-2-enoic acid [714,1122,[1177][1178][1179][1180][1181] [1176,1213] This would apply to molecules capable of exerting their antioxidant activity through two or more of the above-described mechanisms. ...
Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.
... In this sense, flavonoids retard hydrogen-peroxide-mediated oxidation of oxyhemoglobin to methemoglobin, in which ferrylhemoglobin is formed as an intermediate. Additionally, Kassa et al. (2021) found that pre-exposure to sickle cell methemoglobin and its reduced form with 5-fold molar excess of caffeic acid for 48 h reduced the formation of ferryl species in the presence of hydrogen peroxide. Therefore, these findings suggest that caffeic acid may bind to the protein, either covalently or non-covalently, and interfere with the reaction with hydrogen peroxide. ...
... Like other proteins, heme proteins can form conjugations with polyphenols, and covalent modifications can alter the properties of the heme proteins. Kassa et al. (2021) studied the anti-sickling effect of caffeic acid on sickle cell hemoglobin. Following incubation of caffeic acid with sickle cell hemoglobin, adduction sites of the phenolic acid on the hemoglobin molecule were confirmed by mass spectrometry and identified as Cysteine-93 and Cysteine-112 residues of the β-subunit and Cysteine-104 residue of α-subunit. ...
Lipid oxidation is a major cause of quality deterioration that decreases the shelf-life of muscle-based foods (red meat, poultry, and fish), in which heme proteins, particularly hemoglobin and myoglobin, are the primary pro-oxidants. Due to increasing consumer concerns over synthetic chemicals, extensive research has been carried out on natural antioxidants, especially plant polyphenols. The conventional opinion suggests that polyphenols inhibit lipid oxidation of muscle foods primarily owing to their strong hydrogen-donating and transition metal-chelating activities. Recent developments in analytical techniques (e.g., protein crystallography, nuclear magnetic resonance spectroscopy, fluorescence anisotropy, and molecular docking simulation) allow deeper understanding of the molecular interaction of polyphenols with heme proteins, phospholipid membrane, reactive oxygen species, and reactive carbonyl species; hence, novel hypotheses regarding their antioxidant mechanisms have been formulated. In this review, we summarize five direct and three indirect pathways by which polyphenols inhibit heme protein-mediated lipid oxidation in muscle foods. We also discuss the relation between chemical structures and functions of polyphenols as antioxidants.
... It has been shown that among many polyphenolic compounds as caffeic acid could be considered as one of the most potent and promising antimicrobial agents. [13][14][15] Rosmarinic acid (RA) is an ester of caffeic acid. The antibacterial activity of rosmarinic acid have been reported. ...
... A user-friendly software program, Byos (Protein Metrics, Cupertino, CA) is used to identify and quantify percentage modification for a given site of Hb and Mb. Peptides and the site of modification may be determined using the software based upon tandem mass spectrometry (MS2) fragmentation (determined by a peptide spectrum match score) along with inspection of MS1 isotope plots and extracted ion chromatograms (XIC) (Kassa et al., 2021). In cases in which multiple MS2 plots are obtained, the one chosen is the one with the best combination of i) acceptable mass accuracy from the isotope plots, ii) anticipated intensity of b-and y-ions for the fragmentation type and sequence particularly for residues near the site of modification, and iii) precision regarding the place from which the MS2 was extracted based on the location of indicator dot(s) being within or near the peak in the XIC plot. ...
Conversion of the heme iron in myoglobin (Mb) and hemoglobin (Hb) from Fe2+ to Fe3+is a critical step that causes quality deterioration in muscle foods, such as discoloration and generation of oxidative species, including dissociated heme that oxidize lipids and proteins. Increased solvent access to the heme pocket has been proposed to cause oxidation of the heme iron and decrease heme affinity, although empirical results are lacking. This review introduces plasma induced modification of biomolecules (PLIMB) as an approach to modify amino acids of Mb and Hb and thereby assess solvent access to the heme pocket. After PLIMB, liquid chromatography tandem mass spectrometry (LC-MS/MS) peptide analysis and a user-friendly, software platform is utilized to quantify modified amino acid side chains of the heme proteins. Our current findings indicate that PLIMBàLC-MSMS provides a platform to measure solvent access to portions of the heme pocket environment. Evaluation of PLIMB at additional conditions (e.g. different pH values) is underway to better delineate the role of solvent access to the heme pocket relative to the ‘outer-sphere’ mechanism of heme protein oxidation and the ability of hydrogen bonding to stabilize heme within metHbs. Some aspects of heme protein-mediated lipid oxidation that occur at low O2 partial pressures are discussed in relation to solvent access to the heme pocket. Other approaches to study mechanisms of discoloration and lipid oxidation related to Mb/Hb oxidation and heme loss from metHb are also discussed.
... CA has a wide range of pharmacological activities similar to most phenolic compounds. It exerts its antioxidant effect by scavenging free radicals, such as 2,2′-azino-bis3ethylbenzothiazoline-6-sulphonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) [165], reducing iron ions and chelating metal ions [166]. Additionally, CA exerts potential cardiovascular benefits through antioxidant mechanisms associated with LDL oxidation, NO bioavailability, and blood pressure lowering. ...
Cardiovascular and metabolic diseases are a leading cause of death worldwide. Epidemiological studies strongly highlight various benefits of consuming colorful fruits and vegetables in everyday life. In this review, we aimed to revisit previous studies conducted in the last few decades regarding green-colored foods and their bioactive compounds in consideration of treating and/or preventing cardiovascular and metabolic diseases. This review draws a comprehensive summary and assessment of research on the physiological effects of various bioactive compounds, mainly polyphenols, derived from green-colored fruits and vegetables. In particular, their health-beneficial effects, including antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, cardioprotective, and lipid-lowering properties, will be discussed. Furthermore, the bioavailability and significance of action of these bioactive compounds on cardiovascular and metabolic diseases will be discussed in detail.
... These findings suggest novel strategies of suppressing cholangiocarcinoma growth through extracellular vesiclebased therapeutics. This issue also features a second research article by an author of a highly cited article published previously in the journal ('Differential heme release from various haemoglobin redox states and the upregulation of cellular heme oxygenase-1' [17]): Abdu I. Alayash reports here that the antioxidant caffeic acid has antisickling properties and thus may have therapeutic potential for the treatment of sickle cell disease [18]. We are pleased that these authors' earlier articles have been so well cited in their respective fields and are grateful that the authors have returned to publish their latest work with us. ...
This month, FEBS Open Bio celebrates its 10th birthday. To celebrate the journal's first decade, we present this special anniversary issue, comprised of editorials, reviews, and research articles especially commissioned for the occasion. In this introductory editorial, we invite the reader to join us as we reminisce over the journal's past, celebrate its present, and look forward to its future. To celebrate the journal’s first decade, we present this special anniversary issue, comprised of editorials, reviews and research articles especially commissioned for the occasion. This issue has been a year in the making, and we are sure there is something to interest everyone in its virtual pages. But first, please join us as we reminisce over the journal’s past, celebrate its present and look forward to its future.
