title: Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice.
abstract: Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Chu
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Qianhang
authors.initials: Q
authors.lastname: Shao
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Meijin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Congyuan
authors.initials: C
authors.lastname: Xia
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: c Beijing Hospital of Integrated Traditional and Western Medicine , Beijing , China.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Li
authors.affiliation: d Tianjin University of Traditional Chinese Medicine , Tianjin , China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Lou
authors.affiliation: b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Huang
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.|b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China.
authors.forename: Naihong
authors.initials: N
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002945:Cisplatin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D059748:Proteolysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D036145:Ginsenosides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; C035054:ginsenoside Rg1; D002945:Cisplatin
keywords: Ginsenoside Rg1; Nrf2; cisplatin; liver injury; oxidative stress