Pancreatic lipase inhibitory and antiacne activity of Piper betle: Kinetic studies, in silico docking, and chemical characterization of bioactive compounds

Abstract

Lipases play important roles in obesity and skin infections. Piper betle (Piperaceae) is widely cultivated and used in daily life, and it is a rich source of lead compounds for treating skin infections. This study reveals the anti-acne and pancreatic lipase inhibitory potential of Piper betle leaf extract using in vitro and in silico molecular docking. The inhibitory potential of 13 selected plant extracts was evaluated at various concentrations (5-25 µg/mL). The ethyl acetate extract of Piper betle, which showed strong pancreatic lipase inhibitory activity, was further fractionated by preparative thin-layer chromatography. Eluted bands demonstrating strong inhibitory activity were characterized by high-performance liquid chromatography and gas chromatography. The purified compounds, namely anodendroside E, 2-monoacetate, and SH-cyclopropa[3,4]benz(1,2-e)azulen-5-one, were identified and showed over 90% pancreatic lipase inhibition. The isolated compounds also exhibited strong dose-dependent inhibitory effects on Propionibacterium acnes. These observations were consistent with molecular docking studies, which showed that anodendroside E, 2-monoacetate binds to the allosteric site with a binding energy of -7.0 kcal/mol. This binding site is stabilized by hydrogen and carbon-hydrogen bonds contributed by Phe 354, Asp 130, and Ser 103. These findings suggest that the pancreatic lipase inhibitory and anti-acne effects of Piper betle are attributed to anodendroside E, 2-monoacetate.