HPLC-DAD spectra and HPLC chromatograms of the main constituent compounds of PW. (A) Standard mixture and (B) PW at 230 nm. (1) hesperidin, 16.64 min; (2) glycyrrhizin, 29.74 min; (3) atractylenolide III, 37.46 min. 

HPLC-DAD spectra and HPLC chromatograms of the main constituent compounds of PW. (A) Standard mixture and (B) PW at 230 nm. (1) hesperidin, 16.64 min; (2) glycyrrhizin, 29.74 min; (3) atractylenolide III, 37.46 min. 

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Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)...

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... results of HPLC-DAD analysis, using the mobile phases consisting of 0.1% aqueous trifluoroacetic acid (v/v) and pure acetonitrile with a gradient flow, showed satisfactory separation (Table 1). Optimal absorbance for all analytes (hesperidin, 201 nm; glycyrrhizin, 250 nm; atractylenolide III, 222 nm) was detected at 230 nm (Figure 7). Three of the retention time peaks (hesperidin, 16.64 min; glycyrrhizin, 29.74 min; atractylenolide III, 37.46 min) showed chromatograms of the reference components and a 60% methanol extract of PW (Figure 7). These compounds were identified qualitatively by comparing the retention times and UV wavelengths with those of standard compounds. A previous study reported that hesperidin downregulates NF-κB and its target molecules iNOS and COX-2 in mice [30]. Another study showed that glycyrrhizin inhibits NO and PGE2 production in a bimodal fashion [31]. Additionally, atractylenolide III was shown to inhibit LPS-induced TNF-α and NO production in macrophages [32]. These results suggest the anti-inflammatory activity of PW might be related to active components of PW, including hesperidin, glycyrrhizin and atractylenolide III. ...
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... results of HPLC-DAD analysis, using the mobile phases consisting of 0.1% aqueous trifluoroacetic acid (v/v) and pure acetonitrile with a gradient flow, showed satisfactory separation (Table 1). Optimal absorbance for all analytes (hesperidin, 201 nm; glycyrrhizin, 250 nm; atractylenolide III, 222 nm) was detected at 230 nm (Figure 7). Three of the retention time peaks (hesperidin, 16.64 min; glycyrrhizin, 29.74 min; atractylenolide III, 37.46 min) showed chromatograms of the reference components and a 60% methanol extract of PW (Figure 7). These compounds were identified qualitatively by comparing the retention times and UV wavelengths with those of standard compounds. A previous study reported that hesperidin downregulates NF-κB and its target molecules iNOS and COX-2 in mice [30]. Another study showed that glycyrrhizin inhibits NO and PGE2 production in a bimodal fashion [31]. Additionally, atractylenolide III was shown to inhibit LPS-induced TNF-α and NO production in macrophages [32]. These results suggest the anti-inflammatory activity of PW might be related to active components of PW, including hesperidin, glycyrrhizin and atractylenolide III. ...

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... The AWKUM Zoology Department's ethics committee approved the whole experiment to be conducted. Subsequently, xylene can cause inflammation [20]. ...
... One of the substances that caused inflammation was xylene [20]. The sides of both ears were treated with two drops of xylene. ...
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The chitin and chitosan biopolymers are extremely valuable because of their numerous industrial and pharmacological uses. Chitin and chitosan were extracted from the exoskeleton of Periplaneta americana (cockroaches) and termites using various acid and alkali techniques. The extraction process involves an initial demineralization step, during which integument dry powder was subjected to 500 mL (2.07 mol/L) of concentrated HCl at 100 degrees Celsius for 30 min, followed by meticulous rinsing with distilled water to restore the pH to its baseline. Deproteinization was conducted at 80 degrees Celsius using 500 mL (1 mol/L) of NaOH solution, which was repeated for 24 h. A total of 250 mL (0.06 mol/L) of NaOH was added at 100 degrees Celsius for 4 h to obtain chitosan, followed by extensive washing and subsequent drying. FTIR analysis was used to identify the functional groups in Periplaneta americana and termites. The crystallinity of these biopolymers, which have a face-centered cubic structure, was determined by X-ray diffraction analysis. This study assessed the analgesic properties of chitin and chitosan via an acetic-acid-induced writhing test in mice, revealing a significant reduction in writhing behavior following the chitin and chitosan extract. Notably, chitin exhibits the highest degree of analgesic activity compared to chitosan. Both chitin and chitosan show anti-inflammatory effects, with chitosan absorbing proton ions at sites of inflammation, while chitin effectively inhibits ear edema and elicits an analgesic response in mice. Furthermore, the present study revealed antipyretic activity, with termite chitin demonstrating the most significant effect at a concentration of 500 µL/mL, followed by chitosan and chitin at 100 µL/mL. These findings indicate the potential of using chitin and chitosan derived from termites and Periplaneta americana as natural anti-inflammatory compounds, implying prospective uses in anti-inflammatory, antipyretic, and analgesic capabilities.
... The inflammatory response is characterized by redness, edema, increased body temperature, pain, and decreased tissue function caused by various vascular and cellular events . Inflammatory responses induce activation of immune cells such as macrophages, which are the most important inflammatory cells and play a critical role in the inflammatory process by secreting a large number of pro-inflammatory mediators and cytokines, such as nitric oxide (NO), tumor necrosis factor-alpha (TNFα), prostaglandin E2 (PGE2), interleukin-1 (IL-1), IL-6, IL-8 and so on (Oh et al. 2015). So inhibiting their release has become an essential means of treating inflammation. ...
... Acute inflammation induced in a xylene-induced ear swelling model is frequently used to validate the evaluation of anti-inflammatory effect of drugs in vivo (Bitencourt et al. 2011;Oh et al. 2015;Zhang et al. 2018). LPS stimulated RAW264.7 is a well-established in vitro inflammation model (Chen et al. 2014;Feng et al. 2020). ...
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Plant-derived natural compounds are desired for their anti-inflammatory properties. We investigated the chemical composition and the anti-inflammatory effects of the essential oil obtained from leaves of the Chinese medicinal plant Artemisia annua L. Artemisia annua L. essential oil (AO) was obtained by hydrodistillation; the extraction yield was approximately 1.2%. Gas chromatography–mass spectrometry (GC–MS) revealed the presence of 13 compounds in AO; the major compounds were caryophyllene (32.16%), eucalyptol (28.62%), α-pinene (19.08%), and β-pinene (14.72%). Cell counting kit-8 (CCK8) assay revealed that AO did not show in vitro cytotoxicity toward RAW264.7 cells and suppressed the expression of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Pretreatment with AO significantly reduced xylene-induced inflammation in the ears of Kunming mice. AO inhibited inflammatory cell infiltration, decreased epidermis thickness in the ear, and suppressed expression of TNF-α in the serum. The in vivo anti-inflammatory activity of AO was similar to that of the positive control compound Di Song Zhang Bo Cream. Overall, AO was observed to be an effective anti-inflammatory agent. These results provide an experimental basis for commercializing AO-derived external preparations for pharmacological and cosmetic industries.
... The NO levels were determined by the Griess assay, and the PGE 2 , TNF-α, and IL-6 levels were determined with ELISA kits. [21][22][23][24] The IC 50 of each group (excluded the normal and model group) were calculated based determined data, the final experimental results were represented by IC 50 . ...
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Purpose Nonsteroidal anti-inflammatory drugs cause a series of adverse reactions. Thus, the search for new cyclooxygenase-2 selective inhibitors have become the main direction of research on anti-inflammatory drugs. Gentiopicroside is a novel selective inhibitor of cyclooxygenase-2 from Chinese herbal medicine. However, it is highly hydrophilic owing to the presence of the sugar fragment in its structure that reduces its oral bioavailability and limits efficacy. This study aimed to design and synthesize novel cyclooxygenase-2 inhibitors by modifying gentiopicroside structure and reducing its polarity. Materials and Methods We introduced hydrophobic acyl chloride into the gentiopicroside structure to reduce its hydrophilicity and obtained some new derivatives. Their in vitro anti-inflammatory activities were evaluated against NO, TNF-α, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by lipopolysaccharide. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Molecular docking predicted that whether new compounds could effectively bind to target protein cyclooxygenase-2. The inhibitory activity of new compounds to cyclooxygenase-2 enzyme were verified by the in vitro experiment. Results A total of 21 novel derivatives were synthesized, and exhibit lower polarities than the gentiopicroside. Most compounds have good in vitro anti-inflammatory activity. The in vivo activity results demonstrated that 8 compounds were more active than gentiopicroside. The inhibition rate of some compounds was higher than celecoxib. Molecular docking predicted that 6 compounds could bind to cyclooxygenase-2 and had high docking scores in accordance with their potency of the anti-inflammatory activity. The confirmatory experiment proved that these 6 compounds had significant inhibitory effect against cyclooxygenase-2 enzyme. Structure-activity relationship analysis presumed that the para-substitution with the electron-withdrawing groups may benefit the anti-inflammatory activity. Conclusion These gentiopicroside derivatives especially PL-2, PL-7 and PL-8 may represent a novel class of cyclooxygenase-2 inhibitors and could thus be developed as new anti-inflammatory agents.
... Peripherally, coumarin derivatives, another DPS extract constituents, can enhance the removal of free oxygen radicals [73,76,78]. Following the tissue damage, similar to what occurs after intraperitoneal injection of acetic acid, the inflammatory prostaglandins E are produced in the abdominal cavity and help the process of inflammation and intensification of pain, through sensitizing the nerve endings to bradykinin, histamine, and other released transmitters [79]. Coumarin and its derivative, 7-hydroxy coumarin, inhibit the production of such prostaglandins E through inhibition of the cyclooxygenase enzyme systems, resulting in the reduction of inflammation and pain induced by acetic acid [73]. ...
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Purpose of Review Chronic diseases are problematic to health professional specially when using drugs throughout the course of life with un-tolerated side effects. Returning to nature through using nutraceuticals might have both protective and therapeutic effects. Date palm was claimed to be a good source of such nutraceuticals or functional food ingredients. The purpose of the present review was to spot light on the different phytochemicals, phytonutrients, and remedial effects of date palm (Phoenix dactylifera L.) in a goal to be utilized in form of nutraceuticals. The possible mechanisms of action of the remedial effects were among the aim of the study. Recent Findings A protein hydrolyzate prepared from date seed could prevent DNA mutation and susceptibility to cancer. In addition to cancer prevention, date palm fruit improved the treatment outcome of cancer pediatric patients and possesses anti-angiogenic activity as one of the important anticancer mechanisms of action. On the other hand, date seed extracts was recently reported to protect from ulcerative colitis. It seems that all the aforementioned remedial effect might be ascribed to immunoregulatory effect of date palm. These findings proposed that date palm is beneficial for health. Summary Date palm fruit is a rich source of vitamins, minerals, dietary fibers, energy, and easily digestible and absorbable sugars that instantaneously replenish and revitalize the body specially after fasting condition. Mineral contents in date fruits include potassium, phosphorus, magnesium, and calcium. Diverse health claims were reported to belong to various parts of the tree including the edible part of fruits, the seeds, the leaves, spathe (an envelope-like structure that encloses male and female date palm flowers), and pollen grains due to the presence of different bioactive constituents. The main phytochemicals and phytonutrients reported in date palms are phenolic compounds, carotenoids, sterols, anthocyanins, and others. In folk medicine, date palm fruits are used for enhancing immunity and treating gastrointestinal tract disorders, edema, bronchitis, wound, cancer, as well as infectious diseases. However, the exact health benefits and remedial effects of date palm were not fully and deeply investigated. The present review focused on the bioactive constituents and the reported health benefits of date palm and proposed mechanism of action.
... It not only induced anti-inflammatory effects and inhibitory mechanisms in macrophages, but also inhibited activity in vivo. [25] An RCT including 170 patients with FD (86 patients in the PWS group and 84 in the placebo group) evaluated the Nepean Dyspepsia Index (NDI) and FD-QoL at 0, 4, and 8 weeks. [26] The PWS group showed significant improvement in the FD-QoL measure, but not in the total symptom score of NDI when compared to the placebo group. ...
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A considerable number of Asian patients with functional dyspepsia (FD) are searching for complementary and alternative medicine (CAM) because they are unsatisfied with conventional medical treatment. However, no article has focused on CAM for FD from Asian perspective. In Asian countries, many traditional herbal formulas, including Banha-sasim-tang, Soyo-san, Sihosogan-san, Yukgunja-tang, and Pyeongwi-san, are used in patients with FD. In the few blinded and placebo-controlled studies conducted, the weak evidence regarding the effectiveness of herbal prescriptions in patients with FD did not allow any conclusions to be made. The clinical efficacy and safety of STW-5 were proven in several prospective randomized controlled trials and systematic reviews. Hence, it was recently approved as a therapeutic option for the treatment of FD. Peppermint and caraway, FDgard, black seed oil, and Jollab have been used in patients with FD, but there is limited evidence supporting their use. Reviews of acupuncture in patients with FD showed inconsistent results: a Cochrane review reported a negative result, while other meta-analyses reported positive results. Psychotherapy, including hypnotherapy, psychoanalytic psychotherapy, and cognitive behavioral therapy, may be used in patients with FD, although it is only supported by weak evidence. Therefore, well-planned, large-scale studies are necessary to evaluate the efficacy of CAM in treating FD, especially in Asian countries.
... The mRNA expression level of inducible nitric oxide synthase (INOS), Heme Oxygenase-1 (HO-1), and heat shock proteins 70 and 90 beta (HSP) genes was also measured in kidney and liver tissues of all groups. A separate quantitative RT-PCR reaction was conducted for each gene via the 7500 Fast system (Applied Biosystem 7500, Clinilab, Egypt) using 2 × SYBR Green Master Mix (Thermo Scientific, USA) and the primer sequences shown in Table 1 [28][29][30]. The mRNA expression level of the β actin housekeeping gene was measured using the primers sequences reported in Table 1 to standardize the expression levels of the amplified genes. ...
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Increased human exposure to cadmium compounds through ingesting contaminated food, water, and medications causes negative long-term health effects, which has led to the focus of recent researches on finding natural antioxidants to mitigate cadmium-induced toxicity. Therefore, the current study was undertaken to estimate the possible ameliorative effect of chocolate coadministration on acute cadmium chloride (CdCl2)–induced genomic instability and mitochondrial DNA damage in mice liver and kidney tissues. Concurrent administration of chocolate with CdCl2 dramatically decreased the DNA damage level and the number of apoptotic and necrotic cells compared to mice given CdCl2 alone. Extra-production of reactive oxygen species and increased expression of inducible nitric oxide synthase and heat shock proteins genes caused by CdCl2 administration were also highly decreased after chocolate coadministration. Conversely, chocolate coadministration restored the integrity of the mitochondrial membrane potential disrupted by CdCl2 administration, as well as the mitochondrial DNA copy number and expression level of heme oxygenase-1 gene were significantly upregulated after chocolate coadministration with CdCl2. Thus, it was concluded that the coadministration of chocolate alleviated CdCl2-induced genomic instability and mitochondrial DNA damage through its antioxidative and free radical scavenging capabilities, making chocolate a promising ameliorative product and recommended for inclusion in the daily human diet.
... Acetic acid-induced writhing test has long been used as model for testing peripherally acting analgesics (Oh et al., 2015). Administration of acetic acid induces pain by instigating increase in the levels of prostaglandins (PGE2 and PGEF2a) in peritoneal fluid, involving in part peritoneal receptors and inflammatory pain by causing capillary permeability (Patil et al., 2012 andAlemu et al., 2012). ...
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Phoenix dactylifera fruits, commonly known as date fruits are consumed worldwide because of their nutritional and pharmacological values owing to their nutrients and phytoconstituents compositions. This study was undertaken to evaluate and compare anti-inflammatory and analgesic activities of methanol and n-hexane extracts of P. dactylifera fruits in Wistar rats. Egg albumin and carrageenan-induced inflammation models were used to evaluate the anti-inflammatory activities, while acetic acid and formalin-induced pain models were used to evaluate the analgesic activities in Wistar rats. Each model comprised of eight groups of three rats each. Groups administered with 300 mg/kg bw and 600 mg/kg bw of the n-hexane and methanol extracts, respectively exhibited maximum percentage inhibition. The maximum percentage inhibitions of methanol extract on egg albumin and carrageenan, acetic acid and formalin-induced pain at 600 mg/kg bw. (67.24% and 64.22%, 63.33% and 65.32%, respectively) were significantly higher (p < 0.05) than that of the n-hexane extract at 300 mg/kg bw. (56.90% and 52.94%, 50.00% and 52.56%, respectively). Conclusively, both extracts possess anti-inflammatory and analgesic activities, with methanol extract showing greater activity. These activities may be due to the presence of tannins, saponins, but most especially flavonoids in both extracts.
... Xylene-induced swelling can induce the release of TNF-α, IL-6 or other cytokines and inflammatory mediators to stimulate the development of inflammation [38]. To date, many TCVMs are proven to have anti-inflammatory activities. ...
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The extensive use of antibiotics has caused the global spread of multidrug-resistant bacteria and genes, seriously reducing antibiotic efficacy and threatening animal and human health. As an alternative, traditional Chinese veterinary medicine (TCVM) was used in this study for its lack of drug resistance and low toxicity. Huangqin-honghua-pugongying-jinyinhua extract (HHPJE), a novel TCVM, consists of the extracts of Huangqin (Scutellaria baicalensis), Honghua (Carthami Flos), Pugongying (Taraxacum) and Jinyinhua (Lonicerae Japonicae Flos), and was developed to treat bovine mastitis. In this study, we evaluated the toxicity, bacteriostatic, analgesic, anti-inflammatory, and antipyretic activities of HHPJE. Our results show that HHPJE did not show any acute oral toxicity and can be considered safe for oral administration. Additionally, HHPJE possessed a dose-dependent antibacterial effect on Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae and Streptococcus dysgalactiae. HHPJE (60, 30 and 15 g/kg) can reduce the abdominal pain by 44.83 ± 7.69%, 43.15 ± 9.50% and 26.14 ± 4.17%, respectively. The percentages of anti-inflammation inhibition (60, 30 and 15 g/kg) were 35.34 ± 2.17%, 22.29 ± 2.74% and 12.06 ± 3.61%, respectively. The inhibition rates (60, 30 and 15 g/kg) of antipyretic activity were 82.05%, 65.71% and 52.80%, respectively. The evaluation of pharmacodynamics and toxicity indicate that HHPJE possesses significant bacteriostatic, analgesic, anti-inflammatory and antipyretic potential, and also that it is safe for acute oral toxicity, which means it has potential value for treating bovine mastitis in future and alleviating clinical symptoms with no drug resistance or side effects.
... Also, Previous studies, consistent with other studies, indicate that T. Parthenium and its active ingredients reduce NO concentration by inhibiting the expression and synthesis of the iNOS [31,32]. However, there are differences in the amount and type of these compounds that have different reasons. ...
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Background and Aim: Medicinal plants contain various biological compounds, including phenols, flavonoids, and terpenoids, with anti-radical and anti-inflammatory activities that affect human health and improve life. Considering the numerous beneficial effects of Tanacetum Parthenium and Satureja Montana and the lack of full antioxidant capacity and anti-inflammatory effects of their combination, we decided to combine these two plants’ anti-inflammatory and antioxidant effects on induced acute inflammation in BALB/c mice. Methods & Materials: In the present study, mice received the extracts of T. Parthenium and S. Montana and their combination by gavage for 14 consecutive days. Then, to induce acute inflammation, thioglycollate was injected intraperitoneally to all groups. FRAP and Grease tests were used to evaluate the total antioxidant capacity and serum nitric oxide concentration, respectively. One-way ANOVA analyzed the results. Ethical Considerations: This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: REC.1398.021). Results: The results showed that the combination of the extracts (P=0.006) and Satureja Montana (P=0.021) led to a significant increase in total antioxidant activity compared to the control group. Also, according to the results of grease test, Satureja montana (P=0.04), Tanacetum parthenium (P=0.034), and their combination (P=0.003) significantly reduced serum nitric oxide production compared to the control group. Conclusion: The present study shows the synergistic effect of the combined extracts to increase their total antioxidant capacity and anti-inflammatory.
... According to Fialho et al. (2017), the production of prostaglandins could induce the sensitization of nociceptors to prostaglandins, which is related to abdominal constrictions. The writhing may be due to the production of prostaglandins (PG) in peritoneal exudates after acetic acid injection via the cyclooxygenase pathway (Oh et al., 2015). The extract could have molecules that may block the production of inflammation mediators such as prostaglandins. ...
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Antinociceptive evaluation of the aqueous bark extract of Zanthoxylum zanthoxyloides (Lam.) Zepern. and Timler (Rutaceae) on albino wistar rats ABSTRACT Objectives: This study aimed to investigate the phytochemistry and the analgesic activity of the aqueous bark extract of Zanthoxylum zanthoxyloides (AZZ) on albino Wistar rats. Methodology and Results: Phytochemical screening was done using colorimetric reactions and precipitations. Writhing, glutamate, and hot plate tests were used for antinociceptive assessment. The animals were given the extract (400 and 800 mg/kg) and standard drugs, orally. The phytochemical screening has revealed chemical components like alkaloids and flavonoids. The extract displayed significant antinociceptive activity (p < 0.05). At 400 and 800 mg/kg, the extract reduced the writhing by 33.51% and 54.74% respectively. Licking reduction was observed after 15 and 20 minutes of glutamate injection in groups that received extract at 800 and 400 mg/kg, respectively. For the hot plate test, the extract effect was obtained from the 30 th to the 90 th minutes. Conclusions and application of findings: This study finding corroborates the traditional use of Zanthoxylum zanthoxyloides species. This activity may be due to the presence of some chemical groups confirmed by the phytochemical screening such as flavonoids and alkaloids. The mechanism for the antinociceptive activity could be due to the inhibition of the synthesis of some inflammatory mediators such as prostaglandins and nitric oxide (NO). The plant Z. zanthoxyloides, particularly its bark, could be a potent source for the development of new analgesic drugs. Further researches about the safety and characterization of its effective ingredient are needed.