Cytotoxic cycloartane triterpenoid saponins from Actaea vaginata and their mechanism of action

Abstract

A further phytochemical investigation of the whole plants of Actaea vaginata afforded two new cycloartane triterpenoid saponins, (20S*,24R*)-15α,16β-diacetoxy-20,24-epoxy-9,19-cyclolanostane-3β,25-diol-3-O-β-d-xylopyranoside (1) and (20S)-15β,16β -diacetoxy-18,20-epoxy-3β,25-diol-24-oxo-9,19-cyclolanostan-3-O-β-D-xylo-pyrano-syl-25-O-β-d-glucopyranoside (2), together with four known compounds (3–6). Their structures were established on the basis of extensive analysis of NMR and HRESIMS data as well as by comparison with the reported data in the literature. All the isolates were evaluated for their cytotoxic activities against human hepatocellular carcinoma HepG2 cell line. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values of 36.10 and 27.39 μM, respectively. In addition, beesioside I (6) was found to significantly inhibit proliferation and induce apoptosis in HepG2 cells. A closer examination of underlying mechanism revealed that beesioside I could increase the levels of ROS and caspase-3 and promote phosphorylation of JNK in the JNK signaling pathway. Molecular modeling studies also shed further light on how beesioside I interacted with the key protein kinase.