title: Exploration in the cascade working mechanisms of liver injury induced by total saponins extracted from Rhizoma Dioscorea bulbifera.
abstract: Rhizoma Dioscorea bulbifera, the tuber of Dioscorea bulbifera L., has been used to treat various diseases. However, the clinical application has been limited for its hepatotoxicity. In this study, we explored the cascade working mechanisms of time-dependent hepatotoxicity induced by total saponins extracted from Rhizoma Dioscorea bulbifera (TSRD). Animals were orally administered with TSRD for indicated time period. The adverse effects were determined by histopathology and biochemistry. Similar hepatic index was analyzed in L-O2 cells exposed to dioscin for different durations. We found that TSRD could initially cause cell damage and cholestasis in rats. With the treatment going on, oxidative stress injury and up-regulation of Cytochromes P450 (CYPs) were observed both in vitro and in vivo. Eventually, TSRD induced mitochondrial permeability results in apoptosis or necrosis. Taken together, we provided evidence for the time-dependent hepatotoxicity of TSRD and created a 3-step injury model to clarify its cascade working mechanisms.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Experiment Teaching Center, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning 530222, Guangxi Province, PR China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Center for Drug Safety Evaluation and Research, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Ji
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Science and Technology, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address: shilehappy@163.com.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000031:analogs & derivatives / Q000633:toxicity; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D027343:Rhizome / Q000737:chemistry*; D012503:Saponins / Q000302:isolation & purification* / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D012503:Saponins; C019357:dioscin; D003577:Cytochrome P-450 Enzyme System; D004144:Diosgenin
keywords: Cascade mechanisms; Dioscin; Liver injury; Rhizoma Dioscorea bulbifera; Saponins