Myrica esculenta fruit extract as a nutraceutical supplement mitigating LPS-induced inflammation through COX-2 and iNOS modulation: integrated in vitro, in vivo, and docking approaches.

Myrica esculenta Buch. -Ham. ex D. Don, traditionally referred to as "Noga Tenga" in Assam and "Soh-Phi" by the Khasi tribe, holds a longstanding place in Indian medicine for antimicrobial, antidiabetic, and respiratory ailments. This study evaluates the anti-inflammatory potential of the methanolic extract of M. esculenta fruit (MEMEF) in LPS-challenged RAW 264.7 macrophages and a complementary in vivo system. Swiss albino male mice (n = 6) were pre-treated orally with MEMEF for seven days followed by a single intraperitoneal dose of LPS (3 mg/kg bw). Serum AST, ALT, ALP, NO, PGE2, and cytokines were measured, and inos and cox-2 mRNA expression was analyzed by qPCR. In vitro, RAW 264.7 cells were pre-treated with MEMEF (16.7 and 33.5 µg/ml) and stimulated with LPS (1 µg/ml) for 24 h. LC-MS analysis identified major phytoconstituents, and molecular docking examined interactions of epigallocatechin-3-gallate, resveratrol, and myricitrin with COX-2 and iNOS. MEMEF pre-treatment significantly reduced LPS-induced elevations of serum biochemical markers and inflammatory mediators, with qPCR confirming downregulation of inos and cox-2 in treated groups. In vitro, MEMEF markedly decreased NO and PGE2 production and suppressed inos and cox-2 expression in activated RAW 264.7 cells. Docking results showed strong binding of epigallocatechin-3-gallate to both target proteins, suggesting a possible contribution of these interactions to the observed anti-inflammatory effects. Overall, MEMEF exhibited anti-inflammatory activity in cellular and animal models, supporting its promise as a therapeutic candidate for inflammation-related disorders and highlighting its value as a source of nutraceutical supplement derived from a traditionally consumed functional fruit.