Oral and Topical Anti-Inflammatory Activity of Jatropha integerrima Leaves Extract in Relation to Its Metabolite Profile

Jatropha integerrima Jacq., family: Euphorbiaceae, is used in India and subtropical Africa to treat different skin conditions. In this study we evaluated the anti-inflammatory activity of J. integerrima leaves extract (JILE) using rat paw edema model. The extract was administered orally (200 and 400 mg/kg) or applied topically as creams at 2.5, 5, and 10% strength. Four hours post-treatment, maximum reduction of edema volume by 63.09% was observed after oral administration of JILE (400 mg/kg) as compared to indomethacin with 60.43%. The extract anti-inflammatory effect was accompanied by a decrease in NO, prostaglandin PGE2, TNF-a and PKC levels by 19, 29.35, 16.9, and 47.83%, respectively. Additionally, topical applications of JILE showed dose dependent reduction in paw edema and resulted in normalized levels of PGE2, TNF-a, and PKC when used as 10% cream. Signs of inflammations were reduced or absent from paw tissue of animals receiving JILE either orally or topically. Finally, liquid chromatography/mass spectrometry analysis of JILE resulted in the annotation of 133 metabolites including 24 diterpenoids, 19 flavonoids, 10 phenolic acid conjugates, 8 cyclic peptides, 6 phytosterols, 4 sesquiterpenes, and 4 coumarins. Several of the annotated metabolites have known anti-inflammatory activity including vitexin, isovitexin, fraxitin, scopeltin, stigmasterol, and many diterpenoidal derivatives.

The Compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01): A Potential Drug for Treatment of Inflammatory Diseases

The compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01) was structurally developed using bioisosteric modifications of a hybrid prototype as formed from fragments of indomethacin and paracetamol. Initially, in vitro assays were performed to determine cell viability (in macrophage cultures), and its ability to modulate the synthesis of nitrite and cytokines (IL-1β and TNFα) in non-cytotoxic concentrations. In vivo, anti-inflammatory activity was explored using the CFA-induced paw edema and zymosan-induced peritonitis models. To investigate possible molecular targets, molecular docking was performed with the following crystallographic structures: LT-A4-H, PDE4B, COX-2, 5-LOX, and iNOS. As results, we observed a significant reduction in the production of nitrite and IL-1β at all concentrations used, and also for TNFα with JMPR-01 at 50 and 25 μM. The anti-edematogenic activity of JMPR-01 (100 mg/kg) was significant, reducing edema at 2–6 h, similar to the dexamethasone control. In induced peritonitis, JMPR-01 reduced leukocyte migration by 61.8, 68.5, and 90.5% at respective doses of 5, 10, and 50 mg/kg. In silico, JMPR-01 presented satisfactory coupling; mainly with LT-A4-H, PDE4B, and iNOS. These preliminary results demonstrate the strong potential of JMPR-01 to become a drug for the treatment of inflammatory diseases.

Antinociceptive Investigations of Niranthin in Complete Freund’s Adjuvant-induced Chronic Pain in Mice

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund’s adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.

Appraisal of Anti-Arthritic Potential of Quercus Leucotrichophora Methanolic Extract in Complete Freund’s Adjuvant Induced Arthritic Rats; a Mechanistic Study

This research work was conducted to validate the folkloric use and therapeutic potential of Quercus leucotrichophora (QL) leaf methanolic and aqueous extracts against inflammation and arthritis and to determine the chemical composition by HPLC. The in-vitro anti-oxidant and anti-inflammatory activities were carried out along with in-vivo assays such as carrageenan induced paw edema, xylene induced ear edema and Complete Freund’s Adjuvant induced arthritis in Wistar rats. The CFA (0.1 ml) was inoculated to the left hind paw at day 1 to induce arthritis and oral dosing with QLME at 150, 300 and 600 mg/kg was begun at 8th day till the 28th day in all groups while methotrexate was given as standard treatment. There was a noteworthy (p<0.05-0.0001) restoration in body weight, paw edema, arthritic index, altered blood parameters and oxidative stress biomarkers in treated rats as compared to diseased group. Moreover, QLME considerably (p<0.0001) downregulated TNF-α, IL-6, IL-1β, COX-2, and NF-κB, while significantly (p<0.0001) upregulated IL-10, I-κB, IL-4 in relation to diseased group. The QLME exhibited no mortality in acute toxicity study. It was concluded that QLME possessed substantial anti-inflammatory and anti-arthritic potential at all dosage levels, mainly at 600 mg/kg might be due to presence of quercetin, sinapic acid and ferulic acid.

Evaluation of the antipyretic and anti-inflammatory potential of aqueous fruit pulp extract of Terminalia bellirica (Combretaceae) v1

Introduction: Inflammation and fever are common clinical manifestations of many deadly diseases. Members of the genus Terminalia were discovered to have the ability to alleviate inflammation and fever. As a result, this research examined the in-vivoanti-inflammatory and antipyretic properties of aqueous fruit pulp extract of Terminalia bellirica in mice and rats. Methods: The acute and subacute anti-inflammatory effects of the plant were evaluated using Carrageenan-induced paw edema. The antipyretic effect of the plant was evaluated using Baker’s yeast-induced pyrexia model. The extract was given to three experimental groups (9 mg/kg, 18 mg/kg, and 36 mg/kg), with Indomethacin 10 mg/kg and Paracetamol 100 mg/kg servings as positive controls for anti-inflammatory and antipyretic tests, respectively. Negative controls for anti-inflammatory and antipyretic testing were with 1% Gum acacia suspension of 3 ml/kg and 10 ml/kg, respectively. Results: In acute anti-inflammatory activity tests, using the Carrageenan paw edema model, TB18 and TB36 displayed a significant reduction in mean paw edema (P<0.01). In subacute anti-inflammatory activity tests, TB36 displayed a significant reduction in mean paw edema (P<0.01). In Baker’s yeast-induced pyrexia tests, the rectal temperature reduced significantly (P<0.0001) in all experimental groups. Conclusion: In summary, the findings of this study showed that the extract displayed significant anti-inflammatory and antipyretic characteristics in mice and rats accordingly. Keywords: Carrageenan,fever, inflammation, yeast

Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway

Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE made with hexane (Pj-EE-HF), chloroform (Pj-EE-CF), butanol (Pj-EE-BF), or water (Pj-EE-WF) in both in vitro (LPS-induced macrophage-like RAW264.7 cells) and in vivo (carrageenan-induced acute paw edema mouse models) experiments. The most active solvent fraction was selected for further analysis. Various in vitro and in vivo assessments, including nitric oxide (NO), cytokines, luciferase assays, real-time polymerase chain reactions, and immunoblotting analyses were performed to evaluate the underlying mechanisms. In addition, the phytochemical constituents were characterized by Liquid chromatography-tandem mass spectrometry. In in vitro studies, the highest inhibition of NO production was observed in Pj-EE-CF. Further examination revealed that Pj-EE-CF decreased the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells and suppressed subsequent AP-1-luciferase activity by inhibition of phosphorylation events in the AP-1 signaling pathway. Pj-EE-CF treatment also demonstrated the strongest reduction in thickness and volume of carrageenan-induced paw edema, while Pj-EE-BF showed the lowest activity. Furthermore, Pj-EE-CF also reduced gene expression and cytokines production in tissue lysates of carrageenan-induced paw edema. These findings support and validate the evidence that Pj-EE, and especially Pj-EE-CF, could be a good natural source for an anti-inflammatory agent that targets the AP1 pathway.

Anti-inflammatory activity of the topical formulation of Drymoglossum piloselloides (L) Presl. extract on mice

Background: Chronic inflammation of the joints that occur in the condition of gout or osteoarthritis and rheumatoid arthritis often causes repeated inflammation which requires patients to take a long-term pain medication, leading to serious side effects. Alternative treatment especially from herbal ingredients in a topical form is needed. Objective: This study aims to evaluate the anti-inflammatory activity of the leaves extract of Drymoglossum piloselloides (L) Presl. in mice to prove their potential as an anti-inflammatory agent. Methods: Mice were divided into four groups (n=7), namely positive control (sodium diclofenac emulgel), negative control (placebo), P1 (emulgel extract 2.5%), and P2 (emulgel extract 5%). The anti-inflammatory activity test was carried out on mice with carrageenan-induced paw edema by measuring the relative changes in the volume of inflammation at 0 and 3 hours after treatment. Data were analyzed using the Kruskal-Wallis and Mann-Whitney tests with a confidence level of 95%. Results: The emulgel contained flavonoids, triterpenoids, steroids, tannins, and quinones. The anti-inflammatory test showed a significant inhibition of inflammation (p <0.05) at concentrations of 2.5% and 5%. This anti-inflammatory activity could be influenced by the phytochemical compounds contained in the emulgel. Conclusion:Drymoglossum piloselloides (L) Presl. emulgel at concentrations of 2.5% and 5% had an anti-inflammatory activity on mice with carrageenan-induced paw edema. Keywords: inflammation, Drymoglossum piloselloides (L) Presl., emulgel

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.