Asiaticoside Alleviates Liver Fibrosis by Regulating Calcium Signaling Homeostasis
WANG Leijie1, LIN Qihao2, LIN Jiajie2, WANG Jiaxue2, ZHUANG Dongrui2, JIN Yuanting1 *, YAN Zhibin2 *
Liver fibrosis is a vital determinant in the development of chronic liver diseases towards liver cirrhosis and hepatocellular carcinoma. However, there are currently no approved specific agents for effectively halting liver fibrosis. Therefore, the aim of this study was to investigate the potential role of Asiaticoside in combating liver fibrosis and to elucidate the underlying mechanisms. In vitro experiments showed that Asiaticoside markedly inhibited the human LX-2 cells viability and migration, which are known to be participate in fibrosis development. RNA-sequencing was performed on HSCs following Asiaticoside administration, which revealed that the antifibrotic effects of Asiaticoside depend on calcium signaling pathways. Importantly, Asiaticoside induced cytosolic calcium down-regulation while mitochondrial calcium overload. In addition, Asiaticoside also promoted apoptosis, inhibited inflammation and reduced ROS (reactive oxygen species) levels. Asiaticoside significantly alleviated both hepatic collagen deposition and calcium pathways abnormalities, and inhibited the development of liver fibrosis in the CCl4 (carbon tetrachloride)-induced mouse models. In summary, Asiaticoside ameliorated liver fibrosis by calcium signaling pathways, which provides a promising candidate for the clinical treatment of liver fibrosi
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