ABSTRACT
Castanopsis tribuloides belongs to the oak species (Fagaceae) and it is commonly distributed in evergreen forests of Bangladesh, India, Myanmar, Nepal, China, and Thailand. Our present study aimed at uncovering the antipyretic potential of methanol extract of C. tribuloides bark (CTB) in the mice models. Baker's yeast pyrexia model was employed to determine the antipyretic potentials of the extract. Besides, molecular docking and dynamics simulation of CTB phenolic compounds were explored to validate the experimental results and gain insight into the possible antipyretic mechanism of action that can lead to the design and discovery of novel drugs against mPGES-1. The results revealed that CTB (400 mg/kg) significantly inhibited (P < 0.001) the elevated body temperature of mice since 0.5 h, which is more prominent than the standard. At dose 200 mg/kg, the bark extract also produced significant (P < 0.05) antipyretic activity since 2 h. HPLC-DAD analysis identified and quantified nine polyphenolic compounds from the extract, including rutin hydrate, (-) epicatechin, caffeic acid, catechin hydrate, catechol, trans-ferulic acid, p-coumaric acid, vanillic acid, and rosmarinic acid. Molecular docking study suggested probable competition of these phenolic compounds with glutathione, an essential cofactor for microsomal prostaglandin E synthase-1 (mPGES-1) activity. Additionally, RMSF, RMSD, Rg, and hydrogen bonds performed during MD simulations revealed that rutin hydrate (rich in CTB) bound to the mPGES-1 active site in a stable manner and thus inactivating mPGES-1. Therefore, it can be concluded that rutin hydrate reduces pyrexia in mice via downregulating PGE2 synthesis by inhibiting mPGES-1 activity.
