Abstract
Β-sitosterol is a phytosterol, documented to possess various activities including protection against inflammation, diabetes and Alzheimer’s disease. 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 (cyclooxygenase-2 (COX-2) stimulator) and L-Nitro arginine methyl ester (L-NAME) (nitric oxide synthetases (NOS) inhibitor) and L-arginine (nitric oxide 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 the 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 interleukin-6 (IL-6), thiobarbituric acid reactive substances (TBARS) and increased the level of reduced glutathione (GSH). 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 may induce an anti-nociceptive effect via inhibiting the IL-6, oxidative stress, cyclo-oxygenase and nitric oxide.
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KK, LS, AK performed all the experiments and helped in writing the manuscript. RB conceptualized the study.
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The entire study involving the use of mice was approved by the Institutional Animal Ethics Committee (Approval No. (226/CPCSEA/2018/41) and the experiments were conducted according to ethical guidelines of the Ministry of Environment and Forests, Government of India.
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Kaur, K., Singh, L., Kaur, A. et al. Exploring the possible mechanism involved in the anti-nociceptive effect of β-sitosterol: modulation of oxidative stress, nitric oxide and IL-6. Inflammopharmacol 31, 517–527 (2023). https://doi.org/10.1007/s10787-022-01122-8
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DOI: https://doi.org/10.1007/s10787-022-01122-8