Phenylpropanoid derivatives from the fruit of Crataegus pinnatifida Bunge and their distinctive effects on human hepatoma cells

Abstract

Ten undescribed phenylpropanoid derivatives including four pairs of enantiomers and two 8-9' linked neolignans, together with fifteen known ones were isolated from the fruit of Crataegus pinnatifida Bunge. Their structures were established by comprehensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and their absolute configurations were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity of the isolates were evaluated against two human hepatocellular carcinoma, HepG2 and Hep3B cells. Among them, (±)-crataegusanoid A, (±)-crataegusanoid B and crataegusanoid F exhibited moderate cytotoxicity. Interestingly, the different absolute configurations of (±)-crataegusanoid A and B demonstrated enantioselective cytotoxicity in HepG2 cells. Further flow cytometry analysis indicated that both (-)-crataegusanoid A and (-)-crataegusanoid B performed more significant effects on cell apoptosis, autophagy, and cell cycle progression compared with their enantiomers (+)-crataegusanoid A and (+)-crataegusanoid B. In addition, the results revealed that these two pairs of enantiomers induced protective autophagy in HepG2 cells.

Keywords: Autophagy; Cell apoptotic; Cell cycle arrest; Crataegus pinnatifida Bunge; Cytotoxicity; Enantiomers; Rosaceae.