Carrageenan-induced Paw Edema Model Research Articles

Analgesic and Anti-Inflammatory Activity: A Comprehensive Review on Invitro and In Vivo Screening Methods

Modern pharmacotherapy includes analgesic and anti-inflammatory medicines as essential components to relieve pain and inflammation brought on by a variety of medical diseases. Robust screening techniques are essential for the identification of possible candidates with appropriate safety and effectiveness profiles in the search and development of new analgesic and anti-inflammatory medications. This study looks at the many screening methods used in preclinical studies to assess new drugs' analgesic and anti-inflammatory quality. Conventional techniques like the tail flick, hot plate, and writhing’s tests measure analgesic activity by having animals respond to unpleasant stimuli. Comparably, anti-inflammatory activity is frequently assessed using assays like the cotton pellet granuloma test, which gauges tissue granuloma formation, and the carrageenan-induced paw edema model, which measures inflammation. These traditional techniques offer insightful information about the pharmacological effects of test substances. Despite the wide range of screening techniques available, each strategy has advantages and disadvantages. Preclinical studies are more reliable and have higher predictive value when various assays and techniques are integrated into a tiered screening strategy. Furthermore, the successful translation of preclinical findings to human applications depends on taking into account translational variables including species differences and clinical relevancies. As a result, choosing the right screening techniques is critical to the effective identification and characterization of new analgesic and anti-inflammatory drugs.

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.

Analgesic, Anti-Inflammatory, and Chondroprotective Activities of Siraitia grosvenorii Residual Extract.

Inflammation is crucial to osteoarthritis (OA) pathogenesis. The aim of this study was to evaluate Siraitia grosvenorii residue extract (NHGRE) obtained by extracting S. grosvenorii fruits with water as a potential food supplement for treating arthritis based on its analgesic, anti-inflammatory, and chondroprotective effects and the remaining residue with 70% ethanol. We observed the analgesic activity of NHGRE based on the acetic acid-induced writhing response in mice, examined its anti-inflammatory efficacy against carrageenan-induced paw oedema in mice, and investigated its effect on inflammatory cytokine expression in interleukin (IL)-1β-induced SW1353 cells. Furthermore, we determined its effects on cartilage protection in interleukin-1β (IL-1β)-treated SW1353 cells. NHGRE at 200 mg/kg significantly reduced the acetic acid-induced writhing response and prevented oedema formation in the carrageenan-induced paw oedema model. In IL-1β-induced SW1353 cells, NHGRE at 400 µg/mL reduced the expression of inflammation mediators such as tumour necrosis factor (TNF)-α (55.3%), IL-6 (35.4%), and prostaglandin E2 (PGE2) (36.9%) and down-regulated the expression of matrix metalloproteinase (MMP)-1 (38.6%), MMP-3 (29.3%), and MMP-13 (44.8%). Additionally, it restored degraded collagen II levels in chondrocytes. NHGRE plays a protective role in chondrocytes by regulating Nuclear factor kappa B (NF-κB) activation. Overall, NHGRE may be a useful therapeutic agent for OA by controlling pain, oedema formation, and inflammation-related mechanisms.

Exploring the Anti-Inflammatory Potential of Cyperus pangorei Rhizome Extracts An In Vitro and In Vivo Study

Background and aim: Inflammation is a pivotal process implicated in various physiological and pathological conditions, necessitating the exploration of alternative anti-inflammatory agents with minimal side effects. This study aimed to investigate the anti-inflammatory potential of the standardized ethyl acetate (EtAc) fraction derived from Cyperus pangorei rhizomes. Methods: The rhizomes of C. pangorei were collected, processed, and subjected to extraction and fractionation to obtain the EtAc fraction. RP-HPLC analysis was employed to standardized the EtAc fraction against standard quercetin, luteolin, and apigenin. In vitro studies utilized peritoneal macrophages isolated from male Swiss albino rats to assess NO production and cytokine levels (IL-1β, IL-6, TNF-α) upon treatment with the EtAc fraction. In vivo evaluation was conducted using a carrageenan-induced rat paw edema model. Results: RP-HPLC analysis revealed the presence of quercetin, luteolin, and apigenin in the EtAc fraction. In vitro studies demonstrated dose-dependent inhibition of LPS-induced NO production and suppression of inflammatory cytokines (IL-1β, IL-6, TNF-α) by the EtAc fraction. Furthermore, in the carrageenan-induced rat paw edema model, the EtAc fraction exhibited dose-dependent inhibition of paw edema. Conclusion: The findings of this study highlight the significant anti-inflammatory potential of C. pangorei rhizome extracts, particularly the EtAc fraction. The identified compounds, quercetin, luteolin, and apigenin, contribute to its anti-inflammatory activity by modulating key inflammatory mediators. These results support the potential therapeutic use of C. pangorei in managing inflammation-related disorders. Further research is warranted to elucidate the underlying mechanisms and evaluate the long-term efficacy and safety of C. pangorei extracts as anti-inflammatory agents.

Sodium Cromolyn Modulates Carrageenan-Induced Acute Inflammation Through the Interleukin-6 Levels

Background: Previous studies have indicated that sodium cromolyn does not negatively affect steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: This study aimed to investigate the anti-inflammatory effects of sodium cromolyn on carrageenan-induced paw edema in rats and assess its impact on IL-6, an anti-inflammatory cytokine. Methods: The carrageenan-induced paw edema model is widely used for studying inflammatory mechanisms and evaluating anti-inflammatory drugs. The test groups received intraperitoneal injections of sodium cromolyn at doses of 25, 50, and 100 mg/kg alongside a positive control group (indomethacin at 5 mg/kg) and a negative control group (which received the solvent, saline). Thirty minutes after drug administration, carrageenan (1% w/v) was injected into the right hind paws of the rats. Changes in paw volume were measured using a plethysmometer at 0.5, 1, 2, and 3 hours post-carrageenan injection. Blood and paw tissue samples were collected three hours after carrageenan administration, and IL-6 levels were determined using the standard rat Interleukin-6 ELISA kit. Results: The plasma and tissue IL-6 levels in the group treated with cromolyn (25 mg/kg) were significantly higher than those in the positive control group (indomethacin 5 mg/kg). Sodium cromolyn at a dose of 25 mg/kg had a negligible effect on reducing paw edema and IL-6 levels in serum and paw tissues compared to indomethacin (5 mg/kg). The IL-6 levels in plasma and tissues for the group receiving 50 mg/kg of cromolyn were not significantly different from those in the indomethacin group (5 mg/kg). However, IL-6 levels in the group treated with 100 mg/kg of cromolyn were significantly lower than those in the indomethacin group. Among the groups treated with sodium cromolyn, the highest and lowest IL-6 levels were observed in the groups receiving 25 mg/kg and 100 mg/kg of sodium cromolyn, respectively. The anti-inflammatory effects of sodium cromolyn at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg were analyzed, revealing that 25 mg/kg of cromolyn sodium was not significantly effective at any time point (P < 0.05). Additionally, no significant differences (P < 0.05) were observed between the 50 mg/kg and 100 mg/kg doses at any study hour. Sodium cromolyn at a 50 mg/kg dose was as effective as indomethacin (5 mg/kg) in significantly reducing paw edema. Conclusions: Sodium cromolyn, at doses of 50 and 100 mg/kg, effectively reduced paw edema and the concentration of serum and paw tissue IL-6 (P < 0.05), demonstrating significant anti-inflammatory activity. Sodium cromolyn at a 50 mg/kg dose is recommended as the anti-inflammatory dose of this drug.

Broad spectrum antimicrobial, anti-inflammatory and peripheral analgesic activities of heteroaryl nitazoxanide analogs

Background The antiparasitic drug nitazoxanide possesses diverse biological activity. However, very few investigation was accomplished with nitazoxanide analogs. Therefore, herein we focused on the screening of bioactivities using some nitazoxanide-like synthesized molecules. Objectives Four heteroaryl nitazoxanide analogs synthesized in our laboratory were investigated for antimicrobial, anti-inflammatory, and analgesic activity. Materials and methods Disc diffusion method was used for assessing antimicrobial potency against several Gram-positive bacteria, Gram-negative bacteria, and fungi. Carrageenan-induced rat paw edema model was performed to evaluate anti-inflammatory activity. The analgesic property was evaluated using the acetic acid-induced writing inhibition method in the mice model. Molecular docking simulations against cyclooxygenase-1, cyclooxygenase-2, phospholipase A2, NF-κB inducing kinase, and interleukin-1 receptor-associated kinase 4 were also performed. Results and conclusion All the synthesized compounds exhibited broad spectrum antimicrobial property against a number of Gram-positive, Gram-negative species and unicellular fungi. Compound 4 or N-(5-nitrothiazol-2-yl)-furan-3-carboxamide emerged as the most prominent antimicrobial agent exhibiting zone of inhibition ranging in 14–22 mm. These zone diameters are sometimes greater than that displayed by nitazoxanide. Compounds 2 and 3 also showed remarkable broad-spectrum antimicrobial activity with a zone of inhibition 10–20 mm and 12–20 mm, respectively. Compound 4 also displayed potential anti-inflammatory activity which is comparable to standard aceclofenac. Compound 4 also showed mild analgesic effects. The compounds also exhibited moderate binding affinities against the selected target receptors and enzymes during in silico molecular docking. Heteroaryl nitazoxanide analogs showed prominent broad-spectrum antimicrobial, anti-inflammatory, and mild analgesic properties. This study indicates that heteroaryl nitazoxanide analogs might be interesting candidates for new drug discovery.

In vivo Anti-Inflammatory and Antinociceptive Activity Evaluation of Brassica Rapa Ssp. Chinensis Ethanolic Extract with In Vitro Thrombolytic and Anthelmintic Activity Test

Objective: Brassica rapa ssp. chinensis is a well-known vegetable plant (Family: Brassicaceae) often grown as a type of Chinese cabbage. The present study was designed to explore the thrombolytic, anthelmintic, anti-inflammatory, and antinociceptive activities of ethanolic extract of the Brassica rapa ssp. chinensis leaves. Methods: The in vitro thrombolytic activity of the leaf extract was evaluated by clot analysis using Streptokinase as a standard drug. The in vitro anthelmintic activity was assessed by applying four different concentrations of the plant extract (10 mg/ml, 20 mg/ml, 40 mg/ml, and 60mg/ml) and recording the time of paralysis and death of worms. Two different doses (100mg/kg and 250mg/kg b.w.) were administered to evaluate the anti-inflammatory activity of the carrageenan-induced paw edema model. The antinociceptive activity was evaluated by hot plate test in mice by two different doses (200mg/kg and 400 mg/kg b.w.). Results: The ethanolic leave extract had thrombolytic action, which broke up blood clots that had already formed. The ethanolic leaf extract showed both paralysis and faster worm death at those concentrations in the anthelmintic test. The extract showed significant anti-inflammatory action in pedal edema compared to the control group. The results show that the highest level of anti-inflammatory action against carrageenan-induced hind paw edema may be achieved with an ethanolic extract of Brassica rapa ssp. chinensis (250 mg/kg, p.o.). The proportion of maximum possible effect in the hot plate test was 82.49 percent in the antinociceptive evaluation. Conclusion: The pharmacological test of leaf extract endorsed the clinical uses of Brassica rapa ssp. chinensis in treating thrombosis, intestinal worms, and inflammation. Thus, this plant could be subjected to extensive bioactive compounds to discover novel therapeutic agents. Keywords: Brassica rapa ssp. chinensis, ethanolic extract, thrombolytic activity, anthelmintic activity, anti-inflammatory activity, antinociceptive activity

Ziziphus rugosa Leaf: Pharmacognostical Characters and Anti-Inflammatory Properties against Carrageenan-Induced Paw Edema

Ziziphus rugosa belongs to the family Rhamnaceae, which includes many flowering species, primarily trees and shrubs, and sometimes vines. This study aims to describe the pharmacognostic characteristics and potential anti-inflammatory properties of Z. rugosa leaf. The pharmacognostical and preliminary phytochemical studies were performed following standard procedures. Acetone, ethanol, and aqueous extracts were screened for anti-inflammatory potential using the carrageenan-induced paw edema model. Ziziphus rugosa was identified by its evergreen nature, recurved hooks, and drupe-type fruits. Leaves are elliptic/rounded with cordate base exhibiting a dark green glossy upper surface and pubescent lower surface. The leaf exhibited a dorsiventral nature in the transverse section, covering trichomes, collenchyma, sclerenchyma patch, and calcium oxalate crystals as key histological characters. Anamocytic stomata, covering trichomes, crystals, and fragments of vessels, are the imperative elements in powder. The extracts contain carbohydrates, alkaloids, glycosides, tannins, saponins, phenolic compounds, proteins, and flavonoids. The acetone extract at 400 and 200 mg/kg displays a maximum inflammation inhibition of 56.96% and 48.77% among the extracts, and the standard diclofenac sodium inhibits inflammation by 65.61% at 24 hours. The altered liver superoxide dismutase, glutathione, and malondialdehyde levels in the positive control group are significantly near normal in the treatment groups. The histopathological studies of treated animals show significant protection against paw and liver tissue damage. Pharmacognostical study outcomes aid in the identification of species along with ascertaining standardization parameters. Further fractionation of acetone extract followed by isolating compounds responsible for the anti-inflammatory activity would provide an alternative to managing inflammation.

Comparative Study of the Anti-inflammatory Effect of Ethanol Infusion from Cotinus coggygria Heartwood and the Flavonoid Fustin in a Rat Model of Carrageenan-induced Paw Edema

Comparative Study of the Anti-inflammatory Effect of Ethanol Infusion from Cotinus coggygria Heartwood and the Flavonoid Fustin in a Rat Model of Carrageenan-induced Paw Edema

Design, Synthesis, and In Vivo Evaluation of a New Series of Indole-Chalcone Hybrids as Analgesic and Anti-Inflammatory Agents.

Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.

Ameliorative effects of Atriplex crassifolia (C.A.Mey) on pain and inflammation through modulation of inflammatory biomarkers and GC-MS-based metabolite profiling.

Atriplex crassifolia (A. crassifolia) is a locally occurring member of Chenopodiaceae family that has been used in folk medicine for the treatment of joint pain and inflammation. The present study was focused to determine the analgesic and anti-inflammatory potential of the plant. n-hexane (ACNH) and methanol (ACM) extracts of A. crassifolia were evaluated for in vitro anti-inflammatory potential using protein denaturation inhibition assay. In vivo anti-inflammatory potential was determined by oral administration of 250, 500, and 1000mg/kg/day of extracts against carrageenan and formalin-induced paw edema models. Inflammatory mediators such as TNF-α, IL-10, IL-1β, NF-kB, IL-4, and IL-6 were estimated in blood samples of animals subjected to formalin model of inflammation. Analgesic activity was determined using acetic acid-induced writhing and tail flick assay model. Phytochemical profiling was done by GC-mass spectrophotometer. The results of in vitro anti-inflammatory activity revealed that both ACNH and ACM displayed eminent inhibition of protein denaturation in concentration-dependent manner. In acute in vivo carrageenan-induced paw edema model, both extracts reduced inflammation at 5th and 6th hour of study (p < 0.05). A. crassifolia extracts exhibited significant inhibition against formalin-induced inflammation with maximum effect at 1000mg/kg. ACNH and ACM significantly augmented the inflammatory mediators (p < 0.05). Levels of TNF-α, IL-6, IL-1β, and NF-kB were reduced, while those of IL-4 and IL-10 were upregulated. ACNH displayed maximum analgesic effect at 1000mg/kg, while ACM showed potent activity at 500 and 1000mg/kg. The extracts restored the CBC, TLC and CRP toward normal. GC-MS analysis revealed the presence of compounds like n-hexadecanoic acid, Phytol, (9E,11E)-octadecadienoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, 1-hexacosene, vitamin E, campesterol, stigmasterol, gamma sitosterol in both extracts. These compounds have been reported to suppress inflammation by inhibiting inflammatory cytokines. The current study concludes that A. crassifolia possesses significant anti-nociceptive and anti-inflammatory potential owing to the presence of phytochemicals.

Phytochemical analysis and immunomodulatory activities in vitro and in vivo of Aframomum melegueta K Schum seed extracts.

Aframomum melegueta K Schum (A. melegueta), an herbaceous plant renowned for its medicinal seeds, was investigated for its potential immunomodulatory effects in vitro and in vivo using ethanolic and methanolic extracts. The immunomodulatory effect was evaluated by measuring antibody titers using the agglutination technique, while anti-inflammatory activity was assessed in a carrageenan-induced mouse paw edema model. In vitro immunomodulatory activity was measured by lysozyme release from neutrophils. Additionally, white blood cell counts were analyzed post-extracts treatment. The MTT assay was employed to determine cytotoxicity, and the biochemical parameters of liver toxicity were evaluated. Remarkably, both extracts exhibited a dose-dependent reduction in paw edema (p < 0.001), with the most significant reduction observed at 1g/kg (78.13 and 74.27% for ethanolic and methanolic extracts, respectively). Neutrophil degranulation was significantly inhibited in a dose-dependent manner (p < 0.003), reaching maximal inhibition at 100μg/mg (60.78 and 39.7% for ethanolic and methanolic extracts, respectively). In comparison to the control group, both antibody production and white blood cell counts were reduced. Neither of the extracts showcased any cytotoxicity or toxicity. These findings suggest that A. melegueta extracts exhibit immunosuppressive and anti-inflammatory activities due to the presence of various biomolecules.

Discovery of dibenzyl amide derivatives as novel CXCR4 modulators against inflammatory bowel disease

The CXCR4/CXCL12 chemokine axis demonstrates significant potential in the treatment of inflammatory bowel disease (IBD) due to its crucial roles in inflammatory and immune responses. Modulating the CXCR4/CXCL12 pathway can be an effective therapeutic approach to ameliorate the inflammatory state of IBD. In this study, a novel series of meta-dibenzyl amide derivatives were designed and synthesized based on the lead compound AMD3100 and its structurally modified derivatives. Both in vitro and in vivo assays conclusively established that these compounds exhibited potent CXCR4 antagonism and anti-inflammatory activity. Compound 5t demonstrated superior inhibitory rates of binding affinity and chemotaxis of CXCR4+ cells compared to AMD3100. Furthermore, compound 5t notably reduced swelling volume and tissue thickness in the carrageenan-induced mouse paw edema model. Most importantly, in the dextran sodium sulfate (DSS)-induced colitis model, compound 5t significantly mitigated colonic inflammation on both macroscopic and microscopic levels, while suppressing the expression of inflammatory factors and myeloperoxidase (MPO). These findings unequivocally establish the immense potential of compound 5t in the treatment of IBD.

Anti-inflammatory activity of Codium elongatum on Carrageenan-induced paw edema in Wistar male rats

Inflammation is the physiological defence system of the body to initiate the healing mechanism for tissue and eliminate injurious stimuli. In the present study, the anti-inflammatory activity of Codium elongatum was evaluated. Water extract (250 mg/kg, b.w.) and isolated polysaccharide (500 mg/kg, b.w.) are investigated in the carrageenan-induced rat paw edema model using phenylbutazone as a standard drug. Both water extract and isolated polysaccharide showed significant anti-inflammatory activity by blocking the cyclooxygenase 2 pathway. This is the first report to demonstrate the in-vivo anti-inflammatory activity of Codium elongatum.

Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 μg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

Inter-Varietal Variation in Phenolic Profile, Antioxidant, Anti-Inflammatory and Analgesic Activities of Two Brassica rapa Varieties: Influence on Pro-Inflammatory Mediators.

The present research study aims to appraise the potential of polyphenol-rich extracts from two Brassica rapa varieties on antioxidant, anti-inflammatory and analgesic activities using carrageenan-induced paw edema model in rats. Methanol extracts of peels and pulps of Brassica rapa yellow root (BRYR) and Brassica rapa white root (BRWR) were prepared using the soxhlet extraction technique. All four extracts were analyzed by reversed-phase high-pressure liquid chromatography (RP-HPLC) for the polyphenols, and results showed that 10 phenolic acids and 4 flavonoids were detected. Gallic acid was the major phenolic acid (174.6-642.3 mg/100 g of dry plant material) while catechin was the major (34.45-358.5 mg/100 g of dry plant material) flavonoid detected in the extracts. The total phenolic contents (TPC) of BRYR peel, BRWR peel, BRYR pulp and BRWR pulp extracts were in the range of 1.21-5.01 mg/g of dry plant material, measured as GAE, whereas the total flavonoid contents (TFC) were found in the range of 0.90-3.95 mg/g of dry plant material, measured as QE. BRYR peel extract exhibited the best DPPH radical scavenging activity (IC50, 3.85 µg/mL) and reducing potential as compared with other extracts. The in vivo anti-inflammatory potential was assessed by carrageenan-induced rat paw edema, and the analgesic potential was investigated by a hot plate test. Suppression of biochemical inflammatory biomarkers including C-reactive protein (CRP), rheumatoid factor (RF) and tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) concentration were also determined. Results showed that BRYR peel extracts reduced paw edema and suppressed the production of TNF-α, IL-6, CRP and RF most significantly, followed by BRWR peel, BRYR pulp and BRWR pulp extracts. In addition, histopathology observation also supports the anti-inflammatory effect of peel extracts as being greater than that of root pulp extracts. Moreover, it was observed that the analgesic effect of the root-peel extracts was also more pronounced as compared with root-pulp extracts. It can be concluded that BRYR peel extract has higher phenolic contents and showed higher suppression of TNF-α, IL-6, CRP and RF, with strong antioxidant, anti-inflammatory and analgesic effects.

Antinociceptive and anti-inflammatory potential, and chemical characterization of the dichloromethane fraction of Solanum lycocarpum (Solanaceae) ripe fruits by LC-DAD-MS

Ethnopharmacological relevanceSolanum lycocarpum A. St. Hil. (Solanaceae) is a species from the Brazilian Cerrado, exhibiting several medicinal properties, being used by the population in the treatment of ulcers, bronchitis, asthma and hepatitis, which involve inflammatory processes. Aim of this studyThis study aimed to chemically characterize the dichloromethane fraction (DCM), as well as verify its antinociceptive, anti-inflammatory and antioxidant potential. Materials and methodsThe DCM fraction was obtained by partitioning the ethanol extract. The chemical constituents of the DCM fraction were characterized by LC-DAD-MS. The DPPH and FRAP assays were used to evaluate the antioxidant potential. The carrageenan-induced paw edema model was used to assess the anti-inflammatory effects, and the inflammatory infiltrate was evaluated by qualitative and quantitative histological analyses. The antinociceptive action of the DCM fraction was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. ResultsSteroidal alkaloids solasonine, solasodine and solamargine, as well as the alkaloid peiminine/imperialine and caffeoylquinic acids, were annotated in DCM fraction by LC-DAD-MS. The DCM fraction showed antioxidative action in the in vitro DPPH and FRAP tests, as well as an anti-inflammatory effect for the three evaluated doses of 30, 100 and 300 mg/kg in the fourth and sixth hours after the administration of carrageenan. The histological analyses evidenced considerably reduction in leukocyte migration and the number of polymorphonuclear leukocytes. The study also demonstrated antinociceptive activity for the DCM fraction, which reduced abdominal writhing at three concentrations evaluated, as well as a decrease in paw licking in the formalin-induced nociception test both in the neurogenic phase and the inflammatory phase, with greater effectiveness compared to the anti-inflammatory indomethacin. The DCM fraction also increased the latency time of the animals in the hot plate test 60 min after treatment, although it did not seem to involve the opioidergic system. ConclusionThis work evidenced that the dichloromethane fraction of S. lycocarpum fruit possesses antinociceptive and anti-inflammatory potential, which supports its use in folk medicine for management inflammatory conditions.

Phytochemical inspection and anti-inflammatory potential of Euphorbia milii Des Moul. integrated with network pharmacology approach

The inflammatory reaction is induced by several factors like stimulation of different enzymes, oxidative stress, and production of various proinflammatory mediators. Here, we elucidated the phytochemical profile of Euphorbia milii ethanol extract (EMEE) then, we studied its anti-inflammatory potential using a carrageenan-induced paw edema model in rats. It was found that the average paw edoema weight substantially declined (p < 0.05) by treatment with EMEE (100 mg/kg and 200 mg/kg). Also, it was noticed the immunostaining with cyclooxygenase-2 and tumor necrosis factor-alpha antibodies decreased to a mild positive (score 1) after treatment with EMEE (200 mg/kg). This is along with improvement in the histological findings after examination of the paw tissues with hematoxylin and eosin as it revealed a decrease in the inflammation. Also, EMEE (200 mg/kg) resulted in a significant decline (p < 0.05) in the levels of the proinflammatory mediators (granulocyte–macrophage colony-stimulating factor, monocyte chemoattractant protein-1, inducible nitric oxide synthase, and interleukin-5). Interestingly, it resulted in a substantial increase (p < 0.05) in the levels of the anti-inflammatory interleukins (IL-10 and IL-12). Using the Swiss Target Prediction database, 127 genes were related to the identified metabolites in EMEE, of which 55 target genes were associated with 11 inflammatory disorders, as demonstrated by the DisGeNET database. The PI3K-Akt signaling route, the MAPK signaling pathway, and the Ras signaling pathway were identified as the dominant signaling pathways by the study of annotated genes. Therefore, EMEE requires further clinical investigations as an anti-inflammatory agent.

Antinociceptive and antiinflammatory activities of crude leave extract and solvent fractions of Commelina latifolia Hochst. ex C.B.Clarke (Commelinaceae) leaves in murine model.

Ethnopharmacological relevance: In the past, Ethiopian traditional medicine employed the leaves of the native Commelina latifolia Hochst. ex C.B. Clarke plant to treat wounds, pain, and malaria. Aim of the study: The crude extract and solvent fractions of C. latifolia Hochst. ex C.B. Clarke leaves were examined in the present investigation to determine their ability to have an antiinflammatory effect and provide an antinociceptive effect in animal models. Materials and methods: The leaves of C. latifolia were extracted with 80% methanol, and the CL crude extract was further fractionated with chloroform, pure methanol, and distilled water. The carrageenan-induced paw edema model was used to test the extracts' ability to reduce inflammation. The hotplate model and the acetic acid-induced writhing test on rodents were used to test the extracts' potential antinociceptive effect to reduce pain. Results: Inflammation was decreased by 64.59% with CL crude extract (400mg/kg); 56.34% (400mg/kg) of methanol fraction, 64.59% of aqueous fraction (400mg/kg), and 38.27% of chloroform fraction in the carrageenan-induced inflammatory model. All extracts demonstrated a considerable lengthening of the nociception reaction time in the hot plate test, with a maximum antinociceptive effect of 78.98% (crude extract) and 71.65% (solvent fractions). At a dosage of 400mg/kg, the natural C. latifolia crude extract and aqueous fraction demonstrated considerable antinociceptive effects against acetylsalicylic acid (ASA) during the writhing test (48.83% and 45.37than%, respectively). The current findings support Ethiopia's traditional user's assertions that the herb can alleviate inflammation and pain.

Formulation of Entandrophragma utile into an Herbal Emulgel for the Management of Inflammation.

Introduction: Globally, the incidence of inflammation and inflammatory disorders has continued to rise at an alarming rate. Entandrophragma utile is a species of flowering plant widely distributed in Africa and has been used for the management of sickle cell disease, rheumatism, ocular inflammation, duodenal and stomach ulcers. This research aims to formulate and evaluate an anti-inflammatory herbal emulgel using an extract from Entandrophragma utile stem bark (EUB). Method: Using a carrageenan-induced paw oedema model, the anti-inflammatory efficacy of EUB the extract was assessed. The formulated Entandrophragma utile emulgels (EUE) were characterized, and their anti-inflammatory activity was demonstrated, by utilizing diclofenac emulgel-treated rats with complete Freund's adjuvant (CFA)-induced arthritis model as the positive control group. Results: The emulgels formulated had characterization results within acceptable ranges; pH (4.25-5.80), viscosity (418.9-112.8 mPas), spreadability (25.00-31.82 gcm/s), extrudability (30.86-51.02 g/cm2), and a swelling index of (30-60%). The emulgel produced a concentration-dependent inflammatory inhibition with a peak effect (117.97%) at the end of the 4th week which was comparable to that of commercial diclofenac (127.19%). The phytochemical analysis led to the identification of saponins, flavonoids, phenols, and tannins as active secondary metabolites. Conclusions: The stem bark extract of E. utile possessed noteworthy (p < 0.05) reduction in inflammation in comparison to diclofenac and its emulgel formulation showed enormous potential for treating inflammation and pain.