Phenolic-Enriched Ethyl Acetate Fraction of Chatuphalatika Inhibits HMG-CoA Reductase and Preferentially Improves Hepatic Metabolic Parameters in High-Fat Diet-Fed Mice

Chatuphalatika is a traditional Thai polyherbal formulation whose metabolically active fraction has not been identified. This study fractionated the aqueous extract (CPT) by sequential liquid–liquid partitioning to obtain solvent fractions. The ethyl acetate fraction (CPTX) had the highest total phenolic content and was enriched in hydrolyzable tannins, particularly chebulagic acid. CPTX showed the strongest inhibitory activity against HMG-CoA reductase in vitro. In vivo, C57BL/6 mice were fed a high-fat diet for 12 weeks, then treated with CPT, CPTX, or silymarin for 8 weeks while high-fat diet feeding continued. Both CPT and CPTX improved serum lipid profiles. High-dose CPTX (500 mg/kg) additionally reduced fasting blood glucose, serum ALT, and relative liver weight, without affecting body weight or adipose tissue weights. These findings indicate that phenolic enrichment concentrates the hepatic and lipid-lowering activity of Chatuphalatika. HMG-CoA reductase inhibition was used as a screening criterion to identify CPTX as the active fraction; the in vivo hepatometabolic improvements are consistent with, but do not directly confirm, modulation of cholesterol biosynthesis and hepatic lipid metabolism.