Huanhuan Jin1, Naqi Lian1, Mianli Bian1, Chenxi Zhang1, Xingran Chen1, Jiangjuan Shao2,3, Li Wu1, Anping Chen4, Qinglong Guo5, Feng Zhang1,2,3, Shizhong Zheng1,2,3. 1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China. 2. Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. 3. State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China. 4. Department of Pathology, School of Medicine, Saint Louis University, St Louis, MO, USA. 5. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
Abstract
OBJECTIVES: Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti-hepatic injury effects. However, the effects of oroxylin A on alcoholic liver disease (ALD) remains unclear. The aim of this study was to elucidate the effects of oroxylin A on ALD and the potential mechanisms. MATERIALS AND METHODS: Male ICR mice and human hepatocyte cell line LO2 were used. Yes-associated protein (YAP) overexpression and knockdown were achieved using plasmid and siRNA technique. Cellular senescence was assessed by analyses of the senescence-associated β-galactosidase (SA-β-gal), senescence marker p16, p21, Hmga1, cell cycle and telomerase activity. RESULTS: Oroxylin A alleviated ethanol-induced hepatocyte damage by suppressing activities of supernatant marker enzymes. We found that oroxylin A inhibited ethanol-induced hepatocyte senescence by decreasing the number of SA-β-gal-positive LO2 cells and reducing the expression of senescence markers p16, p21 and Hmga1 in vitro. Moreover, oroxylin A affected the cell cycle and telomerase activity. Of importance, we revealed that YAP pharmacological inhibitor verteporfin or YAP siRNA eliminated the effect of oroxylin A on ethanol-induced hepatocyte senescence in vitro, and this was further supported by the evidence in vivo experiments. CONCLUSION: Therefore, these aggregated data suggested that oroxylin A relieved alcoholic liver injury possibly by inhibiting the senescence of hepatocyte, which was dependent on its activation of YAP in hepatocytes.
OBJECTIVES:Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti-hepatic injury effects. However, the effects of oroxylin A on alcoholic liver disease (ALD) remains unclear. The aim of this study was to elucidate the effects of oroxylin A on ALD and the potential mechanisms. MATERIALS AND METHODS: Male ICR mice and human hepatocyte cell line LO2 were used. Yes-associated protein (YAP) overexpression and knockdown were achieved using plasmid and siRNA technique. Cellular senescence was assessed by analyses of the senescence-associated β-galactosidase (SA-β-gal), senescence marker p16, p21, Hmga1, cell cycle and telomerase activity. RESULTS:Oroxylin A alleviated ethanol-induced hepatocyte damage by suppressing activities of supernatant marker enzymes. We found that oroxylin A inhibited ethanol-induced hepatocyte senescence by decreasing the number of SA-β-gal-positive LO2 cells and reducing the expression of senescence markers p16, p21 and Hmga1 in vitro. Moreover, oroxylin A affected the cell cycle and telomerase activity. Of importance, we revealed that YAP pharmacological inhibitor verteporfin or YAP siRNA eliminated the effect of oroxylin A on ethanol-induced hepatocyte senescence in vitro, and this was further supported by the evidence in vivo experiments. CONCLUSION: Therefore, these aggregated data suggested that oroxylin A relieved alcoholic liver injury possibly by inhibiting the senescence of hepatocyte, which was dependent on its activation of YAP in hepatocytes.
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