Active Cousinia thomsonii Extracts Modulate Expression of Crucial Proinflammatory Mediators/Cytokines and NF[kappa]B Cascade in Lipopolysaccharide-Induced Albino Wistar Rat Model

Introduction: Chronic inflammation is implicated in a multitude of diseases, including arthritis, neurodegeneration, autoimmune myositis, type 2 diabetes, rheumatic disorders, spondylitis, and cancer. Therefore, strategies to explore potent anti-inflammatory regimens are pivotal from a human-health perspective. Medicinal plants represent a vast unexplored treasure trove of therapeutically active constituents with diverse pharmacological activities, including anti-inflammatory properties. Herein, we evaluated Cousinia thomsonii, an edible medicinal herb, for its anti-inflammatory/immunomodulatory properties. Methods: Soxhlet extraction was used to obtain different solvent extracts (hexane, ethyl acetate, ethanol, methanol, and aqueous extract) in increasing order of polarity. In vitro anti-inflammatory assays were performed to investigate the effects of extracts on protein denaturation, proteinase activity, nitric oxide surge, and erythrocyte-membrane stabilization. The most effective extracts, ie, ethyl acetate (CTEA) and ethanol (CTE) extracts (150-200 g) were selected for further in vivo analysis using albino Wistar rats. Wistar rats received varying concentrations of CTEA and CTE (25, 50, and 100 mg/kg) for 3 weeks, followed by a single subplantar injection of lipopolysaccharide. Dexamethasone served as positive control. Blood was obtained from the retro-orbital plexus and serum separated for estimation of proinflammatory cytokines (IL6, IL1[beta], IFN[gamma] and TNF[alpha]). Western blotting was performed to study expression patterns of crucial proteins implicated in the NF[kappa]B pathway, ie, NF[kappa]B p65, NF[kappa]BI p50, and NF[kappa]B2 p52. Histopathological examination was done and gas chromatography-mass spectrometry (GC-MS) carried out to reveal the identity of compounds responsible for ameliorating effects of C. thomsonii. Results: Among five tested extracts, CTEA and CTE showed marked inhibition of protein denaturation, proteinase activity, nitric oxide surge and erythrocyte-membrane hemolysis at 600 [micro]g/mL (P