Affiliation:
1. School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310007, China
2. Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China
Abstract
Age-related hepatic lipid accumulation has become a major health problem in the elderly population. Specnuezhenide (SPN) is a major active iridoid glycoside from an edible herb Fructus Ligustri Lucidi, which is commonly used for preventing age-related diseases. However, the beneficial effects of SPN on age-related liver injury remain unknown. This study aimed to reveal the effect of SPN on age-related hepatic lipid accumulation and the underlying mechanism. D-galactose (D-gal)-induced aging mice were treated with vehicle or SPN for 12 weeks. Treatment of SPN decreased lipid accumulation and inflammation in the liver of D-gal–induced mice. Untargeted and targeted metabolomics showed that the SPN could regulate the bile acid (BA) synthesis pathway and restore the BA compositions in serum, livers, and feces of the D-gal–induced mice. Furthermore, SPN enhanced the protein and mRNA levels of hepatic BAs synthesis enzymes cytochrome P45027A1, cytochrome P4507A1, cytochrome P4507B1, and cytochrome P4508B1. Meanwhile, SPN alleviated D-gal-induced gut dysbiosis and reversed the proportions of microbes associated with bile salt hydrolase activity, including Lactobacillus, Ruminiclostridium, and Butyrivibrio. Our study revealed that SPN attenuated age-related hepatic lipid accumulation by improving BA profiles via modulating hepatic BA synthesis enzymes and gut microbiota.
Funder
Zhejiang Provincial Natural Science Foundation of China
National Natural Science Foundation of China
Subject
Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism