In Vivo and In Silico Evaluation of Analgesic and Hypoglycemic Activities of Methanolic Extract of <i>Codariocalyx gyroids</i>

<i>Codariocalyx gyroides</i> (Roxb. ex Link) Hassk has long been recognized in traditional medicine for its diverse pharmacological attributes. However, its potential hypoglycemic and analgesic properties remain insufficiently elucidated. This study aimed to comprehensively evaluate the in vivo hypoglycemic and analgesic activities of the methanolic extract of <i>Codariocalyx gyroides</i> (MECG), supported by in silico molecular docking analyses to elucidate possible mechanisms of action. The acetic acid-induced writhing assay investigated the analgesic activity in Swiss albino mice. MECG demonstrated dose-dependent efficacy, significantly reducing writhing counts at 200 mg/kg (45.66) and 400 mg/kg (55.11). The hypoglycemic potential of MECG was assessed in a Streptozotocin (STZ)-induced diabetic murine model, where a 200 mg/kg dose elicited a substantial reduction in plasma glucose levels. Complementary in silico analysis identified stigmasterol and lanosterol as key bioactive compounds. Stigmasterol exhibited a superior docking score (-7.9 kcal/mol) against cyclooxygenase-2 (COX-2) relative to diclofenac (-7.2 kcal/mol), suggesting a mechanistic basis for the observed analgesic effects. Lanosterol demonstrated enhanced affinity (-10.3 kcal/mol) for the sulfonylurea receptor, outperforming the standard hypoglycemic agent Glibenclamide (-9.2 kcal/mol). These findings underscore the therapeutic potential of MECG as a dual-acting pharmacological agent, warranting further investigation to validate its clinical applicability in managing pain and diabetes.