Phenylpropanoid-homoisoflavonoid derivatives from the fruits of Hippophae rhamnoides L. and their hepatoprotective and hypolipidemic activities

Abstract

Twelve new phenylpropanoid-homoisoflavonoid derivatives (1-12), including (9→1'')-rutinosyl-12-methyl-6,7-furan-phenylpropanoid-homoisoflavonoids(1-3), (9→1'')-(3''-O-(3''''-methoxy-4''''-cinnamic acid))-(6''→1''')-diglucosylphenylpropanoid-homoisoflavonoids (4-6), (9→1'')-glucosyl-phenylpropanoidhomoisoflavonoids (7-9), 10-methylol-9-rutinosyl-(2''→1'''')-glucosyl phenylpropanoid-homoisoflavonoids (10-12), and eleven phenylpropanoidhomoisoflavonoid derivatives (13-23) were isolated from the fruits of Hippophae rhamnoides L. for the first time, and their structures were identified by extensive spectroscopic data (1D and 2D NMR, MS, IR, UV, etc.), physical and chemical properties, and comparison with references. Among them, compounds (3-5) (12 μM) exhibited moderate hepatoprotective activities with survival rates of 62.40 ± 1.44%, 72.52 ± 1.16%, 65.31 ± 1.21%, respectively. Moreover, compounds (3-5) increased the GSH level, and lowered ALT, AST, LDH levels. Meanwhile, compounds (7-9) (120 μM) displayed moderate inhibition of pancreatic lipase activity with inhibition rates of 67.75 ± 2.03%, 71.81 ± 1.32%, 64.11 ± 1.37%, respectively. Moreover, compounds (7-9) decreased FFA-induced lipid accumulation on HepG2 liver cells, and inhibited triglyceride and intracellular neutral lipid accumulations at the concentration of 60 μM with inhibition rates of 52.93 ± 1.73% and 64.23 ± 1.87%, 44.47 ± 1.16% and 51.62 ± 1.05%, 75.08 ± 2.52% and 74.04 ± 2.39%, respectively. In addition, the preliminary structure-activity relationships, plausible biosynthetic pathways, and molecular docking simulations of the selected compounds are scientifically analyzed and discussed in the work.