Unusual piscidic-acid and isoflavone derivatives from Sophora flavescens Ait. and their hepatoprotective effect.

Phytochemical investigation of the roots of Sophora flavescens afforded nineteen piscidic acid and isoflavone derivatives, including seven undescribed compounds (1-7) and four compounds (9-12) reported here for the first time as natural products. Comprehensive analysis of 1D and 2D NMR data, aided by GIAO NMR/DP4+ analyses, induced circular dichroism (ICD) spectra, calculated electronic circular dichroism (ECD) spectra, and X-ray diffraction analysis, enabled their structural elucidation. Structurally, compounds 1-4 were characterized as unusual heterodimers of furfural with either a piscidic acid or an isoflavone derivative, linked via a methylene group; compounds 5-7 were unusual heterodimers of an isoflavone glucoside with a piscidic acid derivative. Additionally, the absolute configurations of the known piscidic acid analogs, ethyl 2-(4-hydroxybenzyl)tartrate (16) and monobutyl 2-(4-hydroxybenzyl)tartrate (19), were established for the first time, based on a comparison of their NMR data, optical rotation values, and ECD spectra with those of compound 15. All isolates were tested for in vitro hepatoprotective activity at 10 μM using ethanol induced AML-12 cells, with compounds 1-9, 14, 16, and 17 demonstrating more significant efficacy. The hepatoprotective effect of piscidic acid (14) was further evaluated in the acute alcohol-induced liver injury (AALI) model rats. The results revealed that its administration significantly reduced levels of ALT, AST, and T-CHO while enhancing SOD activity, thus representing the validation of its hepatoprotective activity. Mechanistically, 14 alleviates AALI via the MAPK signaling pathway, as evidenced by the downregulation of p-JNK and p-ERK protein expression.