Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway.

Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway.
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甘草根提取物和异甘草酸镁通过上调 Nrf2 通路防止雷公藤甲素诱导的肝毒性

DOI:
10.1080/10717544.2018.1472676
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发表时间:
2018-11
期刊:
影响因子:
6
通讯作者:
Jin J
Jin J
中科院分区:
医学2区
文献类型:
--
作者:
Tan QY;Hu Q;Zhu SN;Jia LL;Xiao J;Su HZ;Huang SY;Zhang J;Jin J

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摘要雷公藤甲素是中药雷公藤的主要生物活性成分,具有多种药理活性,包括抗炎、抗生育、抗肿瘤和免疫抑制作用。然而,毒性和严重的不良反应,特别是肝毒性,限制了雷公藤甲素的临床应用。甘草根提取物含有多种生物活性化合物,具有强效保肝作用。异甘草酸镁是甘草酸的18α-甘草酸立体异构体的镁盐,在中国临床上用于治疗慢性病毒性肝炎和急性药物性肝损伤。本研究的目的是探讨红细胞2因子相关因子2途径的作用,LE和雷公藤甲素对雷公藤甲素诱导的肝毒性的保护作用。采用雷公藤甲素建立L-02细胞和大鼠肝毒性模型,分别在体内外观察LE和雷公藤甲素对肝毒性的保护作用。LE和ESTO对雷公藤甲素诱导的细胞毒性有显著的保护作用。此外,雷公藤内酯醇降低了Nrf 2的mRNA和蛋白水平,下调了Nrf 2靶基因,包括UGT 1A,BSEP和MRP 2,而用LE和ESTA预处理逆转了这些作用。最后,Nrf 2参与的抗氧化反应被激活的存在下,LE和ESTA。
Abstract Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated in vitro and in vivo, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including UGT1A, BSEP, and MRP2, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG.
DOI: 10.1021/bi050943e
发表时间: 2005-09-20
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
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Sun X;Ou Z;Chen R;Niu X;Chen D;Kang R;Tang D
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发表时间: 2014
期刊: PloS one
影响因子: 3.7
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发表时间: 2017-04-01
影响因子: 4.3
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DOI: 10.1039/c6fo00889e
发表时间: 2016-01-01
期刊: FOOD & FUNCTION
影响因子: 6.1
作者:
Fan Yuan-Jing;Wei Wei;Dai Zi-Ling
通讯作者: Dai Zi-Ling