Polydatin attenuates diet-induced nonalcoholic steatohepatitis and fibrosis in mice.
Polydatin attenuates diet-induced nonalcoholic steatohepatitis and fibrosis in mice.
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DOI：
10.7150/ijbs.26086
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发表时间：
2018
影响因子：
9.2
通讯作者：
Lan T
中科院分区：
文献类型：
--
作者：
Li R;Li J;Huang Y;Li H;Yan S;Lin J;Chen Y;Wu L;Liu B;Wang G;Lan T
范围：非酒精性脂肪性肝炎（NASH）的特征是肝细胞中的脂质蓄积和炎性细胞浸润。鉴于虎杖苷的抗氧化和抗炎作用，本研究旨在探讨虎杖苷对NASH及其相关纤维化的药理作用。研究方法：C57 BL/6小鼠用蛋氨酸-胆碱缺乏（MCD）饲料喂养以诱导NASH和肝纤维化，并用或不用白藜芦醇苷（5 mg/kg，每隔一天，i.p）处理4周。用虎杖苷处理软脂酸（PA）诱导的HepG 2细胞。结果如下：虎杖苷可降低血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）、活性caspase-3、TUNEL阳性细胞和甘油三酯含量的升高。此外，虎杖苷给药MCD喂养的小鼠通过下调NOX 4酶减少氧化应激。此外，炎症和CD 68巨噬细胞活化的减少与虎杖苷处理对toll样受体（TLR）-4/NF-κB p65信号通路的抑制相关。虎杖苷还可减轻软脂酸（PA）联合或不联合脂多糖（LPS）攻击的HepG 2细胞的脂质积聚、炎症和凋亡。最后，虎杖苷治疗减少肝纤维化对应于肝纤维化标志物基因表达的减少。结论：这些结果表明，虎杖苷通过抑制氧化应激和炎症来预防NASH和纤维化，突出表明虎杖苷作为预防和治疗NASH的潜在治疗剂。
Scope: Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation in hepatocytes and inflammatory cell infiltration. In view of the anti-oxidative and anti-inflammatory effects of polydatin, the current study aimed to investigate the pharmacological effects of polydatin on NASH and its related fibrosis. Methods: C57BL/6 mice were fed with methionine-choline deficient (MCD) diet to induce NASH and liver fibrosis, and treated with or without polydatin (5 mg/kg, every other day, i.p) for 4 weeks. HepG2 cells induced by palmitic acid (PA) were treated with polydatin. Results: The elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), active caspase-3, TUNEL-positive cells, and triglyceride content were decreased by polydatin treatment. In addition, administration of polydatin to MCD-fed mice reduced oxidative stress by down-regulating NOX4 enzymes. Furthermore, the reduction in inflammation and CD68 macrophage activation correlated with inhibition of toll-like receptor (TLR)-4/NF-κB p65 signaling pathway by polydatin treatment. Polydatin also attenuated lipid accumulation, inflammation and apoptosis in HepG2 cells challenged by palmitic acid (PA) combined with or without lipopolysaccharide (LPS). Finally, the reduction of hepatic fibrosis by polydatin treatment corresponded to a reduction in hepatic gene expression of fibrosis markers. Conclusions: These results suggest that polydatin prevents NASH and fibrosis via inhibition of oxidative stress and inflammation, highlighting polydatin as a potential therapeutic agent for prevention and treatment of NASH.
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DOI：
10.1016/j.bbalip.2014.08.015
发表时间：
2014-11
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Tanaka N;Takahashi S;Fang ZZ;Matsubara T;Krausz KW;Qu A;Gonzalez FJ
通讯作者：
Gonzalez FJ
影响因子：
25.7
作者：
George, J;Pera, N;Farrell, G
通讯作者：
Farrell, G
影响因子：
25.7
作者：
Rinella, ME;Green, RM
通讯作者：
Green, RM
影响因子：
--
作者：
Shiyu S;Zhiyu L;Mao Y;Lin B;Lijia W;Tianbao Z;Jie C;Tingyu L
通讯作者：
Tingyu L
影响因子：
13.5
作者：
Coulon, Stephanie;Legry, Vanessa;Geerts, Anja
通讯作者：
Geerts, Anja