Yang Lanxiang, Yu Siping, Yang Yanhong, Wu Huijuan, Zhang Xueying, Lei Yuting, Lei Zili
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, P.R. China; School of Biological Engineering, Wuhu Institute of Technology, Wenjin West Road 201#, Wuhu 241003, P.R. China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China.
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, P.R. China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China.
Bioorg Med Chem. 2022 Feb 1;55:116598. doi: 10.1016/j.bmc.2021.116598. Epub 2021 Dec 30.
Liver injury mediated by endoplasmic reticulum (ER) stress can cause many kinds of liver diseases including hepatic glucose and lipid metabolic disorders, and long term liver injury would lead to cirrhosis and hepatic cancer. Therefore, effective drugs for treating liver injury are urgent in need. Berberine is a multifunctional drug of traditional Chinese medicine, and it can improve various liver diseases. To study the effects of berberine on ER stress-induced liver injury, tunicamycin was administrated to C57BL/6 mice with or without berberine pre-treatment. H&E staining was used to check the morphology and histology of liver tissues. The serum and liver tissues were harvested to test biochemical indexes and the expression levels of genes related with glucose and lipid metabolism, ER stress and unfold protein response (UPR). 16S rDNA sequence technology was conducted to check the fecal microbiota. Pre-administration with berberine could alleviate the excess accumulation of triglyceride (TG) in the liver of mice treated with tunicamycin. Tunicamycin administration caused significant increase of the expression level of genes related to ER stress and UPR, such as CHOP, Grp78 and ATF6, but the berberine pre-treatment could significantly downregulate the expression level of these genes. Tunicamycin administration resulted in increased ratio of Prevotellaceae to Erysipelotrichaceae at the family level of the fecal microbiota in mice, and this trend was reversed by the pre-treatment of berberine. These results demonstrated that berberine could improve liver injury induced hepatic metabolic disorders through relieving ER stress in hepatocytes and regulating gut microbiota in mice.
内质网（ER）应激介导的肝损伤可引发多种肝脏疾病，包括肝脏葡萄糖和脂质代谢紊乱，长期肝损伤会导致肝硬化和肝癌。因此，迫切需要有效的治疗肝损伤药物。黄连素是一种多功能的中药，它可以改善各种肝脏疾病。为研究黄连素对内质网应激诱导的肝损伤的影响，对C57BL/6小鼠给予衣霉素，部分小鼠预先用黄连素处理。采用苏木精-伊红（H&E）染色检查肝组织的形态和组织学。采集血清和肝组织检测生化指标以及与葡萄糖和脂质代谢、内质网应激和未折叠蛋白反应（UPR）相关基因的表达水平。采用16S rDNA序列技术检测粪便微生物群。预先给予黄连素可减轻衣霉素处理小鼠肝脏中甘油三酯（TG）的过度积累。给予衣霉素导致与内质网应激和UPR相关基因（如CHOP、Grp78和ATF6）的表达水平显著升高，但黄连素预处理可显著下调这些基因的表达水平。给予衣霉素导致小鼠粪便微生物群在科水平上普雷沃氏菌科与丹毒丝菌科的比例增加，而黄连素预处理可逆转这一趋势。这些结果表明，黄连素可通过减轻肝细胞内质网应激和调节小鼠肠道微生物群来改善肝损伤诱导的肝脏代谢紊乱。
