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莫林通过抑制 Wnt/β-连环蛋白信号通路改善体内化学诱导的肝纤维化,并抑制体外星状细胞增殖。

Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.

机构信息

Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.

Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.

出版信息

Toxicol Appl Pharmacol. 2014 Jun 1;277(2):210-20. doi: 10.1016/j.taap.2014.03.008. Epub 2014 Mar 20.

DOI:10.1016/j.taap.2014.03.008
PMID:24657339
Abstract

The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin. To establish the anti-fibrotic effects of morin, the levels of key Wnt signaling molecules which are strongly associated with the signal transduction pathway of HSC activation were measured. Overall, from the in vitro results, it was observed that morin at 50 μM concentration inhibited the proliferation of cultured LX-2 cells, inhibited Wnt signaling and induced G1 cell cycle arrest. The in vivo results further confirmed that morin by downregulating the expressions of GSK-3β, β-catenin and cyclin D1 ameliorated DEN-induced liver fibrosis. Hence morin could be employed as a promising chemopreventive natural supplement for liver fibrosis.

摘要

莫林在 LX-2 细胞(培养激活的人肝星状细胞)和二乙基亚硝胺诱导的大鼠肝纤维化模型中的抗纤维化作用。体外研究旨在确定莫林是否影响培养的 LX-2 细胞的存活,而体内研究旨在评估莫林对二乙基亚硝胺诱导的雄性白化 Wistar 大鼠肝纤维化的抗氧化和抗纤维化作用。监测血清中肝功能酶的活性、肝脂质过氧化物水平、血清抗氧化酶的活性和肝结构,以揭示莫林的抗氧化和保肝特性。为了确定莫林的抗纤维化作用,测量了与 HSC 激活的信号转导途径密切相关的关键 Wnt 信号分子的水平。总的来说,从体外结果可以看出,莫林在 50μM 浓度下抑制培养的 LX-2 细胞的增殖,抑制 Wnt 信号并诱导 G1 细胞周期停滞。体内结果进一步证实,莫林通过下调 GSK-3β、β-连环蛋白和细胞周期蛋白 D1 的表达,改善了 DEN 诱导的肝纤维化。因此,莫林可以作为一种有前途的化学预防肝纤维化的天然补充剂。

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