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Nrf2-mediated liver protection by 18 beta-glycyrrhetinic acid against pyrrolizidine alkaloid-induced toxicity through PI3K/Akt/GSK3 beta pathway

文献类型：期刊论文

作者Wang, Zhangting4; Ma, Jiang1,4; He, Yisheng4; Miu, Kai-Kei4; Yao, Sheng2,3; Tang, Chunping2,3; Ye, Yang2,3; Lin, Ge4
刊名PHYTOMEDICINE
出版日期2022-07-20
卷号102页码:12
关键词Pyrrolizidine alkaloids Herb-induced liver injury 18 beta-glycyrrhetinic acid Liquorice Nuclear factor erythroid-2-related factor 2 PI3K/Akt/GSK3 beta
ISSN号0944-7113
DOI10.1016/j.phymed.2022.154162
通讯作者Lin, Ge(linge@cuhk.edu.hk)
英文摘要Background: Misusage of pyrrolizidine alkaloid (PA)-containing plants or unaware intake of PA-contaminated foodstuffs causes thousands of PA poisoning cases in humans. PA intoxication is accompanied by oxidative stress and subsequent extensive hepatocellular damage. Our previous study has demonstrated that 18 beta-glycyrrhetinic acid (GA), a bioactive constituent of liquorice, prevented PA-induced hepatotoxicity in rats, however the underlying mechanisms remain unclear. Objective: This study aims to explore the mechanisms underlying the hepato-protective effect of GA in combating retrorsine (RTS, a representative toxic PA)-induced liver injury. Methods: Histological and biochemical assessments were employed to evaluate the protective effect of GA on RTS-induced hepatotoxicity in rats. Sulforhodamine B assay, real-time PCR, western blotting, and immunostaining were used to explore the underlying mechanisms in human hepatocytes and rats. Results: Our findings demonstrated that GA alleviated RTS-induced elevation of serum ALT and bilirubin levels, as well as hepatocytes necrosis and sinusoidal endothelial cells (SECs) damage in rats. GA also enhanced the activities and expressions of several antioxidant enzymes through upregulating nuclear factor-erythroid 2-related factor2 (Nrf2). Moreover, inhibition of Nrf2 blocked the hepatoprotective effect of GA against RTS intoxication. Mechanistically, GA increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and enhanced glycogen synthase kinase 3 beta (GSK3 beta) inhibitory phosphorylation at serine 9, thus promoting the nuclear accumulation of Nrf2 and activating its downstream targets. Conclusion: This study for the first time demonstrated that GA exerted protective effects against RTS-induced liver injury by potentiating the Nrf2-mediated antioxidant system through PI3K/Akt/GSK3 beta pathway. The findings indicated that GA may serve as a potential candidate drug for the treatment of PA intoxication.
WOS关键词TRANSCRIPTION FACTOR ; NRF2 ; INHIBITION ; DRUG ; CYTOTOXICITY ; EXPRESSION ; KINASE ; CELLS
资助项目Research Grant Council of Hong Kong SAR (GRF)[14106318] ; Chinese University of Hong Kong Direct Grant[4054656]
WOS研究方向Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种英语
WOS记录号WOS:000830562100003
出版者ELSEVIER GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/302022]  
专题新药研究国家重点实验室
通讯作者Lin, Ge
作者单位1.Guangdong Pharmaceut Univ, Sch Tradit Chinese Med, Guangzhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, 505A,Lo Kwee Seong Integrated Biomed Sci Bldg, Hong Kong, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Zhangting,Ma, Jiang,He, Yisheng,et al. Nrf2-mediated liver protection by 18 beta-glycyrrhetinic acid against pyrrolizidine alkaloid-induced toxicity through PI3K/Akt/GSK3 beta pathway[J]. PHYTOMEDICINE,2022,102:12.
APA Wang, Zhangting.,Ma, Jiang.,He, Yisheng.,Miu, Kai-Kei.,Yao, Sheng.,...&Lin, Ge.(2022).Nrf2-mediated liver protection by 18 beta-glycyrrhetinic acid against pyrrolizidine alkaloid-induced toxicity through PI3K/Akt/GSK3 beta pathway.PHYTOMEDICINE,102,12.
MLA Wang, Zhangting,et al."Nrf2-mediated liver protection by 18 beta-glycyrrhetinic acid against pyrrolizidine alkaloid-induced toxicity through PI3K/Akt/GSK3 beta pathway".PHYTOMEDICINE 102(2022):12.

入库方式： OAI收割

来源：上海药物研究所

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