Anti-inflammatory and inflammation-associated pain-modulating effects of azilsartan in preclinical models

Abstract

Azilsartan, an angiotensin receptor blocker, has been widely used in the treatment of hypertension. Its unique structure is hypothesised to confer multiple pleiotropic effects, including anti-inflammatory and anti-apoptotic properties, with potential antioxidant effects being exploratory. The present study was conducted to evaluate the anti-inflammatory, antinociceptive, and antioxidative properties of azilsartan in thermally and chemically induced nociceptive rodent models. Wistar albino rats (200–250 g) and Swiss albino mice (25–30 g) of either sex were procured from the Central Animal Facility, AIIMS Bhopal. Two doses of azilsartan (1 mg/kg and 4 mg/kg) were investigated after approval from the institutional animal ethics committee. Anti-inflammatory and anti-nociceptive properties were evaluated using chemically induced inflammatory models, including carrageenan, Freund’s complete adjuvant (FCA)-induced arthritis, thermally induced nociceptive models and Aspirin-induced gastric ulcer. Azilsartan produced significant anti-inflammatory effects in chemically induced models. In the carrageenan-induced paw edema model, at 6 h, paw volume was reduced to 1.59 ± 0.02 ml with azilsartan 4 mg/kg vs. 1.86 ± 0.01 ml in controls (32% inhibition, p < 0.01). In the FCA-induced arthritis model, by day 14, joint size was reduced by 27% with azilsartan 4 mg/kg (p < 0.05 vs. control). Histopathological and immunohistochemical analyses demonstrated reduced inflammatory infiltration and decreased TNF-α expression in azilsartan-treated groups. Azilsartan also showed dose-dependent protection against aspirin-induced gastric ulceration, with 36% and 45% inhibition at doses of 1 and 4 mg/kg, respectively (p < 0.001). Mean MDA levels were 350 pg/mL in controls vs. 115 pg/mL with azilsartan 4 mg/kg (p = 0.12). No significant analgesic effect was observed in thermally induced nociceptive models (hot plate and tail flick tests). Azilsartan exhibits significant anti-inflammatory and inflammation-associated pain–modulating effects in preclinical models, but does not demonstrate significant analgesic activity in acute thermal nociception. Not applicable.