Exploring the possible mechanism involved in the anti-nociceptive effect of β-sitosterol: Modulation of oxidative stress, nitric oxide and IL-6

Abstract

Abstract β-sitosterol is a phytosterol, documented to possess various activities including inflammation, diabetes, Alzheimer's disease etc. The current investigation was designed to explore the analgesic potential of β-sitosterol and the possible molecular mechanism involved in the observed effect. β-sitosterol was administered at varying doses of 10, 20, and 40 mg/kg before subjecting the mice to acetic acid and formalin challenges. The number of writhings in acetic acid and the number of flinchings and foot tappings were quantified in the formalin test. For mechanistic studies, substance P (COX-2 stimulator) and L-NAME (NOS inhibitor) and L-arginine (NO precursor) were administered before β-sitosterol treatment. β-sitosterol (10, 20, 40 mg/kg) treatment significantly reduced acetic acid-induced writhings and ameliorated the formalin-induced inflammatory phase dose-dependently. Whereas, 40 mg/kg dose of β-sitosterol abrogated formalin-induced neurogenic phase. Substance-P abrogated the effect of β-sitosterol in both neurogenic and inflammatory phases. Whereas, L-arginine only abrogated the inflammatory phase. In biochemical analysis, β-sitosterol treatment reduced the level of IL-6, TBARS and increased the GSH level. Furthermore, L-arginine and substance-P abrogated the GSH increasing and TBARS lowering effect of β-sitosterol (40 mg/kg). Overall, the current study delineated that β-sitosterol might induce anti-nociceptive effect via inhibiting the IL-6, oxidative stress, cyclo-oxygenase and nitric oxide.