Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/34456
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    標題: Tanshinone IIA Downregulates Lipogenic Gene Expression and Attenuates Lipid Accumulation through the Modulation of LXR alpha/SREBP1 Pathway in HepG2 Cells
    作者: Gao, Wan-Yun
    Chen, Pei-Yi
    Hsu, Hao-Jen
    Lin, Ching-Yen
    Wu, Ming-Jiuan
    Yen, Jui-Hung
    貢獻者: Tzu Chi Univ, Inst Med Sci
    Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Ctr Med Genet
    Tzu Chi Univ, Dept Mol Biol & Human Genet
    Tzu Chi Univ, Dept Life Sci
    Chia Nan Univ Pharm & Sci, Dept Biotechnol
    關鍵字: MAFLD
    tanshinone IIA
    phytochemical
    lipogenesis
    lipid accumulation
    LXR alpha
    日期: 2021
    上傳時間: 2023-11-11 11:53:49 (UTC+8)
    出版者: MDPI
    摘要: Abnormal and excessive accumulation of lipid droplets within hepatic cells is the main feature of steatosis and nonalcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). Dysregulation of lipogenesis contributes to hepatic steatosis and plays an essential role in the pathological progress of MAFLD. Tanshinone IIA is a bioactive phytochemical isolated from Salvia miltiorrhiza Bunge and exhibits anti-inflammatory, antiatherosclerotic and antihyperlipidemic effects. In this study, we aimed to investigate the lipid-lowering effects of tanshinone IIA on the regulation of lipogenesis, lipid accumulation, and the underlying mechanisms in hepatic cells. We demonstrated that tanshinone IIA can significantly inhibit the gene expression involved in de novo lipogenesis including FASN, ACC1, and SCD1, in HepG2 and Huh 7 cells. Tanshinone IIA could increase phosphorylation of ACC1 protein in HepG2 cells. We further demonstrated that tanshinone IIA also could suppress the fatty-acid-induced lipogenesis and TG accumulation in HepG2 cells. Furthermore, tanshinone IIA markedly downregulated the mRNA and protein expression of SREBP1, an essential transcription factor regulating lipogenesis in hepatic cells. Moreover, we found that tanshinone IIA attenuated liver X receptor alpha (LXR alpha)-mediated lipogenic gene expression and lipid droplet accumulation, but did not change the levels of LXR alpha mRNA or protein in HepG2 cells. The molecular docking data predicted tanshinone IIA binding to the ligand-binding domain of LXR alpha, which may result in the attenuation of LXR alpha-induced transcriptional activation. Our findings support the supposition that tanshinone IIA possesses a lipid-modulating effect that suppresses lipogenesis and attenuates lipid accumulation by modulating the LXR alpha/SREBP1 pathway in hepatic cells. Tanshinone IIA can be potentially used as a supplement or drug for the prevention or treatment of MAFLD.
    關聯: BIOMEDICINES, v.9, n.3, pp.326
    顯示於類別:[生物科技系(所)] 期刊論文

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