Xylene-induced Ear Edema In Mice Research Articles

In Rodents, Methanol Extract from Ritchiea capparoides leaf has Analgesic, Anti-Inflammatory, and Antipyretic Properties

Background: Ritchiea capparoides leaves are traditionally used in Southern Nigeria to cure fever, snake bites, aches, and malaria. Consequently, the analgesic, anti-inflammatory, and antipyretic properties of Ritchiea capparoides leaf ethanol extract were assessed in rodents in this work. Methods: Using acetic acid and tail immersion models in mice, the analgesic effect was investigated, and xylene, egg-albumen, brewer's yeast, and dinitrophenol models were used to investigate the anti-inflammatory and antipyretic properties in mice and rats at doses of 125 mg/kg, 250 mg/kg, and 500 mg/kg of the methanol extract. The plant's leaf extract was also subjected to oral acute toxicity testing and phytochemical screening. Results: At p<0.05 and p<0.01, the methanol leaf extract and the common medication (aspirin) considerably reduced the amount of writhes brought on by acetic acid. The reaction times of the tested agent's standard and extract groups significantly increased. The extract significantly reduced oedema in the egg-albumin-induced paw oedema model, with dose-related inhibition of p<0.05 and p<0.01, similar to aspirin. When compared to dexamethasone, Ritchiea capparoides leaf extract likewise showed a significant p<0.05 and p<0.01 effect in the xylene-induced mouse ear oedema test. Rats with pyrexia caused by dinitrophenol and Brewer's yeast both showed a statistically significant decrease in rectal temperatures. Alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, and cardiac glycosides are all present in the methanol leaf extract. It was discovered that the oral acute toxicity testing were more than 5000 mg/kg. Conclusion: The findings supported the traditional use of R. capparoides as a medicine by demonstrating the plant's possible analgesic, anti-inflammatory, and antipyretic properties at the tested concentrations of methanol leaf extract.

Investigations of the highly efficient processing technique, chemical constituents, and anti-inflammatory effect of N-ethyl-2-pyrrolidinone-substituted flavan-3-ol (EPSF)-enriched white tea

N-Ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) are a newly discovered compound class in tea with various bioactivities. This study aimed to develop a novel processing technique to enhance EPSF contents in white tea efficiently. Using optimal processing parameters of 125 °C and 30 min in a high-temperature sterilizing oven, total EPSF content significantly increased by 1.42–18.80-fold to 1.57–6.22 mg/g without impacting sensory characteristics. Metabolomics analysis revealed elevated levels of nucleosides, nucleotides, bases, theaflavins, flavonol aglycones, EPSFs, and most flavone-C-glycosides, as well as decreased levels of amino acids, procyanidins, theasinesins, several flavanols, and flavonol-O-glycosides after EPSF-enrichment treatment. Furthermore, the EPSF-enriched white tea exhibited notable anti-inflammatory effects, mitigating xylene-induced ear edema in mice and carrageenan-induced paw edema and cotton ball-induced granulomas in rats. This study developed a new processing technique for highly efficient enhancement of EPSFs in white tea and demonstrated that EPSF-enriched white tea has a potential to serve as effective anti-inflammatory dietary supplement.

Anti-inflammatory effects and related mechanisms in vitro and in vivo of Hedychium coccineum rhizome essential oil

Ethnopharmacological relevanceHedychium coccineum rhizome is an anti-inflammatory ethnomedicine used to remedy inflammation-related swelling and bronchial asthma. Aim of the studyThe study aimed to analyze the phytochemical constituents of H. coccineum rhizome essential oil (EO) and evaluate its in vitro and in vivo anti-inflammatory effects and underlying mechanisms. Materials and methodsPhytochemical constituents of H. coccineum rhizome EO were analyzed using GC-FID/MS. In RAW264.7 macrophages induced by LPS, blockade of PGE2, NO, IL-1β, IL-6, and TNF-α secretion by H. coccineum rhizome EO was measured, and then Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate its underlying mechanisms. Moreover, we used the xylene-induced ear edema model for testing anti-inflammatory potential in vivo and examined auricular swelling as well as tissue and serum contents of IL-1β, IL-6, and TNF-α. ResultsEO's main components were E-nerolidol (40.5%), borneol acetate (24.8%), spathulenol (4.5%), linalool (3.8%), elemol (3.5%), and borneol (3.4%). In RAW264.7 cells stimulated by LPS, EO downregulated the expression of pro-inflammatory enzyme (iNOS and COX-2) genes and proteins, thereby suppressing pro-inflammatory mediators (NO and PGE2) secretion. Simultaneously, it reduced TNF-α, IL-1β, and IL-6 release by downregulating their mRNA expression. Besides, H. coccineum EO attenuated LPS-stimulated activation of NF-κB (by reducing IκBα phosphorylation and degradation to inhibit NF-κB nuclear translocation) and MAPK (by downregulating JNK, p38, and ERK phosphorylation). In xylene-induced mouse ear edema, EO relieved auricular swelling and lowered serum and tissue levels of TNF-α, IL-1β, and IL-6. ConclusionsH. coccineum EO had powerful in vivo and in vitro anti-inflammatory effects by inhibiting MAPK and NF-κB activation. Hence, H. coccineum EO should have great potential for application in the pharmaceutical field as a novel anti-inflammatory agent.

Chemical composition and biological activities of the Algerian Cymbalaria muralis aerial parts

In the present study we report data about antioxidant (DPPH, β-Carotene, reducing power), anti-inflammatory (xylene-induced ear oedema in mice (76 ± 1.0%) and membrane stabilisation (100%)) and antimicrobial (Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, Pseudomonas arugenosa ATCC27853 and Fusarium oxysporum ATCC62506) activities of the ethanolic extract from the Algerian Cymbalaria muralis P. Gaertn., B. Mey. & Scherb (CME). The LC-ESIMS analysis of CME chemical profile allowed to identify antirrhinoside (1), catalpol (2), linarioside (3), glucosyringic acid (4), angoroside C (5), apigenin 7-O-glucoside (6), acacetin 7-O-β-D-glucopyranoside (7), apigenin (8), chrysoeriol 7-rutinoside (9), diosmin (10) and linarin (11). The evaluated total phenolic and flavonoid contents support the biological activities.

In-vitro and in-vivo anti-inflammatory properties of extracts and isolates of Pangdahai

Background: Pangdahai (matured, ripened, and dried seeds of Scaphium affine (Mast.) Pierre) is widely used in managing several diseases in countries like China, Vietnam, Japan, and India. This study evaluated the anti-inflammatory effects of the crude extracts (ethanol and aqueous) and isolated compounds of Pangdahai. Methods: Xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, and nitric oxide (NO) assay were used to evaluate and screen the crude extracts and isolated compounds from the ethanolic extracts of Pangdahai. TNF-α and IL-1β levels in the tissues of rat foot and ear were determined by ELISA. The cytotoxicity of the isolated compounds was also determined by MTT assay. Molecular docking studies using targets involved in the inflammatory process were also used to further evaluate the compounds. Results: Both aqueous and ethanol extracts demonstrated significant anti-inflammatory effect and markedly attenuated vascular permeability in mice induced by acetic acid in a dose-independent manner. The ethanol extract also significantly inhibited levels of IL-1β and TNF-α. Four (4) compounds exhibited significant inhibitory effects on NO release without cytotoxicity on RAW 264.7 macrophage. These compounds also showed good binding affinities for COX-2, PLA2, IRAK-4 and NIK. ConclusionsThis study validates, provides scientific evidence and justification for the use of the aqueous decoctions of Pangdahai in pharyngitis traditionally. (+) – Pinoresinol, tiliroside, Z-caffeic acid, and 3,4-dihydroxybenzoic acid (protocatechuic acid) isolated from Pangdahai showed anti-inflammatory activities, which might be responsible for the actions of Pangdahai. Tiliroside showed high binding affinity comparable to the native ligands of inflammatory mediators.

Simultaneous Study of Analysis of Anti-inflammatory Potential of Dryopteris ramosa (C. Hope) C. Chr. using GC-Mass and Computational Modeling on the Xylene-induced Ear Oedema in Mouse Model.

In the present study, we aimed to investigate the extraction and identification of the potential phytochemicals from the Methanolic Extract of Dryopteris ramosa (MEDR) using GC-MS profiling for validating the traditional uses of MEDR its efficacy in inflammations by using in-vitro, in-vivo and in silico approaches in anti-inflammatory models. GC-MS analysis confirmed the presence of a total of 59 phytochemical compounds. The human red blood cells (HRBC) membrane stabilization assay and heat-induced hemolysis method were used as in-vitro anti-inflammatory activity of the extract. The in-vivo analysis was carried out through the Xylene-induced mice ear oedema method. It was found that MEDR at a concentration of 20 μg, 30 μg, and 40 μg showed 35.45%, 36.01%, and 36.33% protection to HRBC in a hypotonic solution, respectively. At the same time, standard Diclofenac at 30 μg showed 45.31% protection of HRBC in a hypotonic solution. The extract showed inhibition of 25.32%, 26.53%, and 33.31% cell membrane lysis at heating at 20 μg, 30 μg, and 40 μg, respectively. In comparison, standard Diclofenac at 30 μg showed 50.49% inhibition of denaturation to heat. Methanolic extract of the plant exhibited momentous inhibition in xylene-induced ear oedema in mice treated with 30 μg extract were 47.2%, 63.4%, and 78.8%, while inhibition in mice ear oedema treated with 60 μg extract was 34.7%, 43.05%, 63.21% and reduction in ear thickness of standard drug were 57.3%, 59.54%, 60.42% recorded at the duration of 1, 4 and 24 hours of inflammation. Molecular docking and simulations were performed to validate the anti-inflammatory role of the phytochemicals that revealed five potential phytochemicals i.e. Stigmasterol,22,23dihydro, Heptadecane,8methyl, Pimaricacid, Germacrene and 1,3Cyclohexadiene,_5(1,5dimethyl4hexenyl)-2methyl which revealed potential or significant inhibitory effects on cyclooxygenase-2 (COX-2), tumour necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. The outcome of the study signifies that MEDR can offer a new prospect in the discovery of a harmonizing and alternative therapy for inflammatory disease conditions.

Preliminary Pharmacological Screening of Corchorus olitorius Extracts for Anti-inflammatory and Wound Healing Activity

Aim of present study was to investigate the preliminary screening of aerial part of Corchorus olitorius extracts for anti-inflammatory and wound-healing activity on experimental animals. Different extracts with respective solvents i.e. petroleum ether, chloroform, ethyl acetate, ethanol and aqueous extracts of C. olitorius were obtained by successive solvent extraction. All extracts were screened for anti-inflammatory activity using Xylene-induced ear edema in mice and wound healing effect was studied by using incision wound model in mice. The weight of the ear lobes and biochemical measurements, nitric oxide (NO) levels and MPO in the tissue sample were used to detect the anti-inflammatory effect. The wound healing effect was observed by measurement of tensile strength and protein and hydroxyproline level assessment in the healed tissues. Observations of present study were confirmed that ethanol extract of C. olitorius (EECO) was showed significant (p<0.05) inhibition in the ear edema of mice. NO and MPO activity was decreased significantly in EECO-treated mice. Wound healing potential was observed by significant improvement in tensile strength as well as protein and hydroxyproline level of healed tissue of EECO-treated mice. In conclusion, ethanol extract of C. olitorius was found most effective for anti-inflammatory through reduction of NO and MPO activity as well as wound healing potential in experimental mice.

Investigation of the chemical composition and anti-inflammatory effects of the crude methanolic extract and fractions of Artocarpus heterophyllus (Fam. Moraceae)

Inflammation is a local response of living tissues in mammals towards injury and is normally linked to the pathogenesis of several diseases. In this study, we investigated the anti-inflammatory activity of the methanol extract and the n-hexane, ethyl acetate and butanol fractions of the Jack fruit leaves. Methanolic cold maceration was carried out to get the extract, followed by liquid-liquid fractionation. Two models, viz. xylene-induced ear edema in mice and egg albumin-induced paw edema in rats were used to evaluate them. The anti-inflammatory activity of the extract and fractions was screened for anti-inflammatory activity using xylene-induced ear edema in mice and egg albumin-induced paw edema in rats. The chemical constituents of the extract and fractions were detected by dereplication using HPLC-DAD. Results showed that for the xylene-induced topical edema model, only the 250µg/ear n-butanol fraction exhibited good anti-inflammatory activity at 21.21% when compared with the piroxicam (positive control) at 32.21%. In the egg albumin-induced paw edema both the methanol extract and n-butanol fraction at 250mg/kg and 500mg/kg showed good anti-inflammatory activity after 2hours post-administration, with maximum effect at 6 hours. Specifically, at 6 hours the methanol extract at 250 mg/kg exhibited 41.21% inhibition; the butanol fraction at the same dose exhibited 43.63% inhibition when compared with piroxicam (500 mg/kg) with 38.39% inhibition. The HPLC-DAD analysis of the extract and fractions revealed the presence of six (6) compounds: catechin (1), septicine (2), 5-isoprunetin 8C glucoside (3), naamine (4), protocatechuic acid (5), and vitexin (6). These compounds have been reported to display anti-inflammatory activity. These findings suggest that the leaf extract possess an anti-inflammatory phytocompounds which authenticates their ethno-medicinal usage claim by local people in different parts of Nigeria.

Anti-inflammatory efficacy and relevant SAR investigations of novel chiral pyrazolo isoquinoline derivatives: Design, synthesis, in-vitro, in-vivo, and computational studies targeting iNOS

Isoquinoline alkaloids are a rich source of multimodal agents with distinctive structural specificity and various pharmacological activities. In the present report, we propose a combination of design, synthesis, computational study, primary in-vitro screening using the lipopolysaccharide (LPS)-induced RAW 264.7 cell line, and in-vivo evaluation in mice models as a novel approach to speed up anti-inflammatory drugs discovery. The nitric oxide (NO) inhibitory effect of new compounds revealed that all of them displayed the potent NO inhibitory ability in a dose-dependent manner with no obvious cytotoxicity. A series of the model compounds 7a, 7b, 7d, 7f, and 7g have been identified as the most promising, with IC50 values of 47.76 μM, 33.8 μM, 20.76 μM, 26.74 μM, and 47.8 μM respectively in LPS-induced RAW 264.7 cell line. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. Western blotting data of 7d identified that our synthesized compounds can down-regulate and suppress the expression of the key inflammatory enzyme, inducible nitric oxide synthase (iNOS). These results suggested that synthesized compounds may be potent anti-inflammatory agents, inhibiting the NO-release, in turn, iNOS inflammatory pathways. Furthermore, in-vivo anti-inflammatory detection via xylene-induced ear edema in mice revealed that these compounds could also inhibit swelling in mice, with model compound 7h showing an inhibition activity (64.4%) at a concentration of 10 mg/kg comparable to the reference drug celecoxib. Molecular docking results showed that shortlisted compounds (7b, 7c, 7d, 7e, and 7h) had a potential binding affinity for iNOS with low energies, with S-Score to be −7.57, −8.22, −7.35, −8.95, −9.94 kcal/mol, respectively. All results demonstrated that the newly synthesized chiral pyrazolo isoquinoline derivatives are highly potential anti-inflammatory agents.

Synthesis, Characterization and Pharmacological Evaluation of Ethanolic Extract of Sarcostemma brevistigma for its Anti-inflammatory and Antipsoriatic Activity

The goal of this work was to test the anti-inflammatory and anti-psoriatic properties of an ethanolic extract of Sarcostemma brevistigma stem in the formation of a hydrogel utilizing several mouse models. The methanolic fraction was obtained by fractionating an ethanolic extract of Sarcostemma brevistigma stem with methanol. Viscosity, spreadability, drug release profile, pH, homogeneity, physical properties and irritant impact of the prepared hydrogel were assessed. Percentage inhibition, nitric oxide (NO), and myeloperoxidase (MPO) levels in mice ears following acute inflammation caused by croton oil were all measured. Physical examination revealed that the produced hydrogels were brownish in color and had a homogenous and smooth look when applied. All other test criteria, including as pH, viscosity, spreadability, and consistency, were determined to be acceptable in the F3 hydrogel formulation. The optimal F3 formulation component was 1.5 g of Carbopol 940 and 1% sodium CMC. In xylene-induced ear edema in mice, the percent suppression of edema was found to be equivalent to the standard group of therapy (69.58 %). The results of this investigation show that a produced hydrogel of SB extract has inhibitory activity on acute inflammation. The capacity of croton oil to promote neutrophil influx in mouse ear tissue was shown in this study. Treatment with extract hydrogels, as well as Voltaren Emulgel, substantially decreased MPO and NO levels in mice ears (P < 0.01). The presence of flavonoids in Sarcostemma brevistigma may explain why the methanol extracts have a substantial anti-inflammatory effect.

Synthesis and Anti-Inflammatory Activity of 1-Methylhydantoin Cinnamoyl Imides

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans-cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1β in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1β. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.

Hedychium flavum flower essential oil: Chemical composition, anti-inflammatory activities and related mechanisms in vitro and in vivo

Ethnopharmacological relevanceHedychium flavum, an ornamental, edible, and medicinal plant, is extensively cultivated as a source of aromatic essential oils (EO). Its flower is a traditional Chinese medicine for treating inflammation-related diseases like indigestion, diarrhea, and stomach pain. In particular, H. flavum flower EO has been used in cosmetics and as an aromatic stomachic to treat chronic gastritis in China. Aim of the studyThis research aimed to analyze H. flavum flower EO's chemical composition and explore its anti-inflammatory activities and related mechanisms in vitro and in vivo. Materials and methodsEO's chemical composition was determined by GC-FID/MS analysis. For in vitro test, the anti-inflammatory activity of EO was demonstrated by measuring the LPS-induced release of NO, PGE2, IL-1β, TNF-α, and IL-6 in RAW264.7 macrophages, and then its related mechanisms were explored using qRT-PCR, western blot, and immunofluorescent staining analysis. Next, EO's in vivo anti-inflammatory potential was further evaluated using a xylene-induced ear edema model, in which ear swelling and TNF-α, IL-6, and IL-1β levels in serum and tissue were examined. ResultsThe main components of EO were β-pinene (20.2%), α-pinene (9.3%), α-phellandrene (8.3%), 1,8-cineole (7.1%), E-nerolidol (5.4%), limonene (4.4%), borneol (4.1%), and β-caryophyllene (3.7%). For the anti-inflammatory activities in vitro, EO dramatically reduced the LPS-stimulated NO and PGE2 release by suppressing the mRNA and protein expression of iNOS and COX-2. Meanwhile, it remarkably decreased IL-6, TNF-α, and IL-1β production by inhibiting their mRNA levels. Related mechanism studies indicated that it not only inhibited IκBα phosphorylation and degradation, leading to blockade of NF-κB nuclear transfer but also suppressed MAPKs (ERK, p38, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. Further in vivo assay showed that EO ameliorated xylene-induced ear edema in mice and reduced TNF-α, IL-6, and IL-1β levels in serum and tissue. ConclusionsH. flavum EO exerted significant anti-inflammatory activity in vivo and in vitro, and its mechanism of action is related to the inhibition of MAPK and NF-κB activation. Thus, H. flavum EO could be considered a novel and promising anti-inflammatory agent and possess high potential for utilization in the pharmaceutical field.

Phillygenin from Forsythia suspensa leaves exhibits analgesicpotential and anti-inflammatory activity in carrageenan-induced paw edema in mice.

Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1β, NO, and PGE2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. PRACTICAL APPLICATIONS: Phillygenin is one of the major active ingredients in Forsythia suspensa. But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.

Formulation and Evaluation of Ocimum Sanctum based Emulgel for Wound Healing Potential

The purpose of this study was to evaluate the anti-inflammatory effect of leaves of Occimum sanctumin the formulation of hydrogels using different types of animal models. Materials and Methods: O. sanctum leaf ethanol extract was fractionated with methanol to give a methanol fraction. The methanol fraction (1% vw / w) was used in hydrogel formulations in various combinations of Carbopol 940 and sodium CMC. The hydrogels produced were characterized for optimal physical properties, pH, ductility, uniformity, viscosity, release profile, and irritation. Optimized hydrogels were evaluated for anti-inflammatory activity in animals using xylene-induced, croton oil-induced ear edema, and cotton pellet-induced granuloma models. The effect was monitored by , which measures the suppression rate of ears , nitric oxide (NO) and myeloperoxidase (MPO) levels in mice after acute inflammation induced by croton oil. Results and discussion: Physical evaluation confirmed that the resulting hydrogel was brownish in color and had a uniform and smooth appearance when applied. The combination of F3-hydrogel formulations was found to be appropriate for all other evaluation parameters such as pH, viscosity, spreadability and consistency. Therefore, it was observed that the optimal composition of F3 preparation is 1.5 g of Carbopol 940 and 1% sodium CMC. The suppression rate of edema in xylene-induced ear edema in mice was found to be comparable to that of the standard treatment group (65.59%). In this study, the results show that the prepared hydrogel-OSMFH has an inhibitory effect on acute inflammation. The results show the ability of croton oil to induce the influx of neutrophils into the ear tissue of mice.

HPLC Analysis, Acute toxicity and Assessment of Antioxidant and Anti-inflammatory Capacity of different Extracts of Equisetum arvense

Equisetum arvense, a medicinal plant belonging to the family of Equisetaceae, is used in the fight against infectious or inflammatory diseases. The aim of this research was to assess the acute oral toxicity, to identify some phenolic acids and flavonoids by HPLC analysis, and to evaluate the antioxidant and the anti-inflammatory activities of E. arvense methanol extract (EAME) and aqueous (EAQE) extracts. The acute toxicity study was carried out using Swiss albino mice. Animals were observed during 14 days and signs of toxicity were controlled, afterwards, mice were sacrificed for biochemical studies. HPLC method was used to analyze E. arvense extracts. Antioxidant activity was determined using DPPH, reducing power, free hydroxyl radicals assays and antihemolytic activity. Xylene-induced ear edema in mice and carrageenan-induced paw edema in rat were used to evaluate anti-inflammatory activity. Formaldehyde-induced paw edema was used to assess anti-arthritic effect of extracts. In the acute toxicity study, both extracts did not engender any mortality or changes in general behaviors of tested animals. The LD50 was found to be superior to 5000 mg/kg DW. Extracts, rich in polyphenols and/or flavonoids, showed high antioxidant activity. Both extracts showed significant anti-inflammatory and anti-arthritic effects on animal models. These results revealed that E. arvense extracts can be a valuable source of phenolic compounds and flavonoids with powerful antioxidant and anti-inflammatory properties.

Optimization for ultrasonic-microwave synergetic extraction of total iridoid glycosides and screening of analgesic and anti-inflammatory active fractions from patrinia scabra Bunge (Valerianaceae)

BackgroundPatrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction.MethodP. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out.ResultsThe content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities.ConclusionPatrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities.

Elucidation of the anti-inflammatory mechanism of Er Miao San by integrative approach of network pharmacology and experimental verification

Traditional Chinese medicine (TCM) has been long time used in China and gains ever-increasing worldwide acceptance. Er Miao San (EMS), a TCM formula, has been extensively used to treat inflammatory diseases, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the underlying mechanisms of EMS in treating human rheumatoid arthritis (RA) and other inflammatory conditions. Quercetin, wogonin and rutaecarpine were probably the main active compounds of EMS in RA treatment as they affected the most RA-related targets, and TNF-α, IL-6 and IL-1β were considered to be the core target proteins. The main compounds in EMS bound to these core proteins, which was further confirmed by molecular docking and bio-layer interferometry (BLI) analysis. Moreover, the potential molecular mechanisms of EMS predicted from network pharmacology analysis, were validated in vivo and in vitro experiments. EMS was found to inhibit the production of NO, TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells; reduce xylene-induced mouse ear edema; and decrease the incidence of carrageenan-induced rat paw edema. The carrageenan-induced up-regulation of TNF-α, IL-6 and IL-1β mRNA expression in rat paws was down-regulated by EMS, consistent with the network pharmacology results. This study provides evidence that EMS plays a critical role in anti-inflammation via suppressing inflammatory cytokines, indicating that EMS is a candidate herbal drug for further investigation in treating inflammatory and arthritic conditions.

Anti-Inflammatory, Antioxidant, Chemical Characterization, and Safety Assessment of Argania spinosa Fruit Shell Extract from South-Western Morocco.

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC50 of DPPH, ABTS, reducing power, and β-carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities.

Chemical constituents and anti-inflammatory activity of the total alkaloid extract from Melodinus cochinchinensis (Lour.) Merr. and its inhibition of the NF-κB and MAPK signaling pathways

BackgroundMelodinus cochinchinensis (Lour.) Merr. is a medicinal plant, which is used as a folk medicine for treating meningitis and fractures. However, the anti-inflammatory activity of total alkaloid extract from M. cochinchinensis (MCTA) and its molecular mechanism are still not studied. PurposeThe aim of this study is to investigate the main chemical constituents of MCTA and explore its anti-inflammatory potential in both in vitro and in vivo assessments. MethodsUHPLC-ESI-HRMS/MS was applied to analyze the chemical profiling. The anti-inflammatory efficacy of MCTA was evaluated on lipopolysaccharide (LPS) induced RAW 264.7 cells and two common inflammation models in mice. The production of pro-inflammatory mediator and cytokine was tested using the ELISA method. The pathological change was analyzed by histological assessment. The expression of NF-κB, MAPKs and PPAR-γ proteins was evaluated using western blot analysis. ResultsA total of 21 monoterpenoid indole alkaloids (MIAs) were characterized by UHPLC-ESI-HRMS/MS. Aspidospermine- and quinolone-type alkaloids were found to be the major compounds. MCTA significantly decreased the production of NO, IL-1β, IL-6 and TNF-α in LPS-induced RAW 264.7 macrophages. MCTA significantly inhibited the phosphorylation of ERK1/2, JNK and p38 MAPK, suppressed the NF-κB transcriptional activation and improved the PPAR-γ expression. Moreover, the in vivo experiment exhibited that MCTA pretreatment markedly alleviated the xylene-induced ear edema and carrageenan-induced paw edema in mice and decreased the IL-1β, IL-6 and TNF-α expressions. ConclusionMCTA is rich in MIAs and exhibited a significant inhibitory effect on the production proinflammatory cytokines. The mechanism might be related to the inhibition of activation of NF-κB and MAPK pathways.

Anti-nociceptive, anti-inflammatory and antipyretic activities of the ethanol root bark extract of Salacia lehmbachii in rats and mice

Background: The decoction of the roots of Salacia lehmbachi is used in traditional medicine for the treatment different diseases such as malaria pains diabetes and microbial infections.Methods: Phytochemical screening and oral acute toxicity tests were carried out on the ethanol root extract of the plant. Anti-nocicetive activity using acetic acid induced writhing and tail immersion method in mice, anti-inflammatory activity using carrageenan induced paw oedema in rats and xylene induced ear oedema test in mice and antipyretic activity using Brewer’s yeast and D-amphetamine induced pyrexia in rats were determined at 50 mg/kg, 100 mg/kg and 200 mg/kg doses of the root extract.Results: The ethanol root extract contain alkaloids, saponins, tannins, flavonoids, terpenoids, steroids and cardiac glycosides. The oral acute toxicity tests was found to be greater than 5000 mg/kg. The root extract and the standard drug (Aspirin) significantly (p<0.05 and p<0.01) decreased the number of writhes caused by acetic acid. The extract and morphine significantly (p<0.05 and p<0.01) prolonged reaction time in tail immersion model. The extract produced significant (p<0.05 and p<0.01) dose dependent inhibition of oedema which was comparable to aspirin in carrageenan induced paw oedema model. The root extract also demonstrated significant (p<0.05 and p<0.01) effect in xylene induced mouse ear oedema test compared to dexamethasone. The extract significantly decreased high temperature in both Brewer’s yeast and d-amphetamine induced pyrexia.Conclusions: Findings show that S. lehmbachii may provide a good source of plant compounds with analgesic, anti-inflammatory and antipyretic activities.