School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Molecules. 2023 Feb 16;28(4):1874. doi: 10.3390/molecules28041874.
Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases, which in turn triggers mild inflammation, metabolic dysfunction, fibrosis, and even cancer. Accumulating evidence has suggested that Berberine (BBR) could significantly improve MAFLD progression. Clock and Bmal1 as heterodimer proteins highly participated in the development of MAFLD, but whether BBR targets Clock and Bmal1 in MAFLD remains poorly understood. The result suggested that the protein levels of Clock and Bmal1 were decreased in MAFLD mice, which was negatively correlated with elevated reactive oxygen species (ROS) accumulation, the HO level, liver inflammation, metabolic dysfunction, and insulin resistance. The mRNA and protein levels of Clock and Bmal1 were also decreased in glucosamine-induced HepG2 cells, which were are negatively related to glucose uptake, the ROS level, and the HO level. More importantly, Bmal1 siRNA could mimic the effect of glucosamine in HepG2 cells. Interestingly, Berberine (BBR) could rescue metabolism disorder and redox homeostasis through enhancing Clock and Bmal1 expression in vivo and in vitro. Therefore, BBR might be an effective natural compound for alleviating redox homeostasis, metabolism disorder, and liver pathological changes in MAFLD by activating Clock and Bmal1 expression.
代谢相关性脂肪性肝病（MAFLD）是最常见的慢性肝病之一，它会引发轻度炎症、代谢功能障碍、纤维化，甚至癌症。越来越多的证据表明，小檗碱（BBR）可以显著改善 MAFLD 的进展。Clock 和 Bmal1 作为异二聚体蛋白，高度参与 MAFLD 的发生，但 BBR 是否靶向 MAFLD 中的 Clock 和 Bmal1 尚不清楚。结果表明，Clock 和 Bmal1 的蛋白水平在 MAFLD 小鼠中降低，与活性氧（ROS）积累增加、HO 水平、肝炎症、代谢功能障碍和胰岛素抵抗呈负相关。在氨基葡萄糖诱导的 HepG2 细胞中，Clock 和 Bmal1 的 mRNA 和蛋白水平也降低，与葡萄糖摄取、ROS 水平和 HO 水平呈负相关。更重要的是，Bmal1 siRNA 可以模拟氨基葡萄糖在 HepG2 细胞中的作用。有趣的是，BBR 可以通过增强体内和体外 Clock 和 Bmal1 的表达来纠正代谢紊乱和氧化还原平衡。因此，BBR 可能是一种通过激活 Clock 和 Bmal1 表达来缓解 MAFLD 中氧化还原平衡、代谢紊乱和肝脏病理变化的有效天然化合物。
