Discover the Power of Lithospermic Acid as Human Carbonic Anhydrase VA and Pancreatic Lipase Inhibitor Through In Silico and In Vitro Studies.

ABSTRACT: Obesity remains a significant global health concern, with limited pharmacological options that balance efficacy and safety. In this study, we identified lithospermic acid (LTS0059529) from Salvia miltiorrhiza as a potential dual inhibitor of pancreatic lipase (PL) and human carbonic anhydrase VA (hCA VA), two key enzymes in lipid metabolism. Using molecular docking and dynamics simulations, we observed that lithospermic acid interacts with Zn²⁺ in hCA VA via its benzofuran carboxylate moiety and forms stable complexes with PL through hydrogen bonding with ASP 205 and π-stacking interactions with PHE 77 and PHE 215. Experimental validation confirmed its inhibitory activity, with K_i values of 33.1 ± 1.6 μM for PL and 0.69 ± 0.01 μM for hCA VA. While its inhibition of hCA VA is not

SUBMITTER: Citriniti EL 

PROVIDER: S-EPMC12010950 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature