[Hypolipidemic activity of phenolic acids from Inula japonica Thunb.]

To isolate and identify phenolic acid constituents from methanol extract of Inula japonica Thunb. and evaluate their lipid-lowering activity in vitro.

The methanol extract of Inula japonica Thunb. was purified using silica gel, ODS, and semi-preparative HPLC. The compound structures were determined using physicochemical and spectroscopic analyses, and their hypolipidemic activities were assessed in an AML12 cell model of free fatty acids (FFA)-induced lipid deposition. The active compounds were further assessed for their effects on lipid deposition, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) of the cell model.

A total of 11 phenolic acid compounds were isolated from Inula japonica Thunb., namely dihydrocaffeic acid (1), protocatechualdehyde (2), chlorogenic acid (3), cryptochlorogenic acid (4), 1,3-O-dicaffeoylquinic acid (5), 2,3-dicarboxy-6,7-hydroxy-l-(3',4'-dihydroxy)-phenyl -1,2-dihydronaphthalene-10-methyl ester (6), caffeic acid (7), protocatechuic acid (8), 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxyphenyl)-naphthalene (9), p-hydroxybenzoic acid (10), and 4-hydroxyphenylacetic acid (11). Among them, compounds 1 and 9 were isolated for the first time from the genus Inula, and compound 6 was isolated for the first time from this plant. Compounds 6 and 9 showed lipid-lowering effects in FFA-induced AML12 cells, significantly lowered cellular levels of total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase, reduced lipid accumulation, and alleviated oxidative stress and mitochondrial function.

Inula japonica Thunb. contains diverse phenolic acids, and among them compounds 6 and 9 show hypolipidemic activities via inhibiting lipid accumulation and improving oxidative stress and mitochondrial function and can potentially serve as lead compounds for treatment of metabolic dysfunction-associated steatotic liver disease.