Implication of the Stereoisomers of Ginsenoside Derivatives in the Antiproliferative Effect of HSC-T6 Cells

Abstract

Two ginsenoside derivatives (9, 10) along with 10 known ginsenosides (1-8, 11, and 12) were isolated from BST204, which is a crude ginseng extract fermented by enzyme and acid hydrolysis. The two ginsenosides were determined as 12β,20(S),25-trihydroxydammara-3-O-β-D-glucopyranoside (9) and 12β,20(R),25-trihydroxydammara-3-O-β-D-glucopyranoside (10). Compounds 1-12 were categorized into stereoisomeric pairs differentiated by R- or S-configuration at C-20, the number or position of sugar residues at C-3 or C-6, and the type of derivative at C-21. Their structure-activity relationship was evaluated by the cell viability assay using HSC-T6 cells. Results showed that 20(S) (3 > 4, 7 > 8, and 9 > 10), a 2-hydroxy-2-methylbutyl moiety at C-21 (3, 7 > 9), and the number of sugar residues at C-3 (3 > 7) significantly affected the antiproliferative activity on HSC-T6 cells. The inhibition of the cell proliferation of compound 3 was assessed by annexin-V/PI staining analysis using flow cytometry.