Berberine improves liver injury induced glucose and lipid metabolic disorders via alleviating ER stress of hepatocytes and modulating gut microbiota in mice.
Berberine improves liver injury induced glucose and lipid metabolic disorders via alleviating ER stress of hepatocytes and modulating gut microbiota in mice.
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DOI：
10.1016/j.bmc.2021.116598
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发表时间：
2021-12
影响因子：
3.5
通讯作者：
Lanxiang Yang;Siping Yu;Yanhong Yang;Huijuan Wu;Xueying Zhang;Yuting Lei;Zili Lei
中科院分区：
文献类型：
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作者：
Lanxiang Yang;Siping Yu;Yanhong Yang;Huijuan Wu;Xueying Zhang;Yuting Lei;Zili Lei
内质网应激介导的肝损伤可引起多种肝脏疾病，包括肝脏糖脂代谢紊乱，长期肝损伤可导致肝硬变和肝癌。因此，迫切需要治疗肝损伤的有效药物。黄连素是一种多功能中药，可改善多种肝病。为研究黄连素对内质网应激所致小鼠肝损伤的影响，用衣霉素对C57BL/6小鼠进行了黄连素干预或不加黄连素干预。H&E染色观察肝组织的形态和组织学改变。测定血清和肝组织生化指标及糖脂代谢、内质网应激和未折叠蛋白反应相关基因的表达水平。采用16S rDNA测序技术检测粪便微生物区系。黄连素预先给药可减轻衣霉素所致小鼠肝脏甘油三酯(TG)的过量蓄积。衣霉素可显著上调内质网应激和UPR相关基因CHOP、GRP78和ATF6的表达水平，而黄连素可显著下调这些基因的表达水平。衣霉素可使小鼠粪便微生物区系中普氏菌科与毛菌科的比例增加，而黄连素的预处理则逆转了这一趋势。上述结果表明，黄连素可能通过减轻肝细胞内质网应激，调节肠道微生物区系，改善肝损伤所致的肝代谢紊乱。
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 ofPrevotellaceaetoErysipelotrichaceaeat 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.