Deng Xuehui, Lin Bingfeng, Wang Fang, Xu Pingcui, Wang Nani
School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310007, China.
Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China.
Metabolites. 2023 Aug 18;13(8):960. doi: 10.3390/metabo13080960.
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 , 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 , , and . Our study revealed that SPN attenuated age-related hepatic lipid accumulation by improving BA profiles via modulating hepatic BA synthesis enzymes and gut microbiota.
年龄相关性肝脂质蓄积已成为老年人群中的一个主要健康问题。梓醇（SPN）是一种来自可食用草药的主要活性环烯醚萜苷，常用于预防与年龄相关的疾病。然而，SPN对年龄相关性肝损伤的有益作用尚不清楚。本研究旨在揭示SPN对年龄相关性肝脂质蓄积的影响及其潜在机制。用载体或SPN对D-半乳糖（D-gal）诱导的衰老小鼠进行12周治疗。SPN治疗可减少D-gal诱导小鼠肝脏中的脂质蓄积和炎症。非靶向和靶向代谢组学表明，SPN可调节胆汁酸（BA）合成途径，并恢复D-gal诱导小鼠血清、肝脏和粪便中的BA组成。此外，SPN提高了肝脏BA合成酶细胞色素P45027A1、细胞色素P4507A1、细胞色素P4507B1和细胞色素P4508B1的蛋白质和mRNA水平。同时，SPN减轻了D-gal诱导的肠道菌群失调，并逆转了与胆盐水解酶活性相关的微生物比例，包括[此处原文缺失具体微生物名称]、[此处原文缺失具体微生物名称]和[此处原文缺失具体微生物名称]。我们的研究表明，SPN通过调节肝脏BA合成酶和肠道微生物群改善BA谱，从而减轻年龄相关性肝脂质蓄积。
