title: Paeoniflorin attenuates ANIT-induced cholestasis by inhibiting apoptosis in vivo via mitochondria-dependent pathway.
abstract: Apoptosis induced by the bile acids in the liver is considered to play a pivotal role in the pathogenesis of cholestatic disease. Increasing evidence has demonstrated that Paeoniflorin (PF) exerts therapeutic effect on severe cholestatic liver diseases. However, whether PF could protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by inhibiting apoptosis remains unclear. In this study, we mainly investigated the effect and anti-apoptosis mechanism of PF on cholestasis. Experimental results indicated that PF pretreatment could attenuate liver damage and cholestasis by ANIT in rats, lift the biliary excretion in addition to decrease serum indices (ALT, AST, DBIL, TBIL, TBA, ALP and ϒ-GT) and conspicuous neutrophil infiltration and cell apoptosis in liver evidenced by TUNEL staining. Furthermore, the pro-apoptosis genes expression of Bax, Caspase-9 and Caspase-3 increased by ANIT were prominently reduced after PF treatment. The increase of anti-apoptosis gene and main regulator Bcl-2 in mitochondria by ANIT was largely reversed by PF pre-treatment. In summary, our study demonstrated that PF pre-treatment not only significantly attenuated ANIT-induced cholestasis and liver injury, but also largely reduced cell apoptosis in liver, thus may act as a potential therapeutic agent for cholestasis disease.
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Hou-Qin
authors.initials: HQ
authors.lastname: Zhou
authors.affiliation: Department of Respiration, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Yin-Qiu
authors.initials: YQ
authors.lastname: Huang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Peng-Yan
authors.initials: PY
authors.lastname: Li
authors.affiliation: Department of Integrative Medical Center, 302 Military Hospital of People's Liberation Army, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Jia-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Experimental Laboratory Center, 302 Military Hospital of People's Liberation Army, Beijing, China.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Shi-Zhang
authors.initials: SZ
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Hao-Tian
authors.initials: HT
authors.lastname: Li
authors.affiliation: Department of Integrative Medical Center, 302 Military Hospital of People's Liberation Army, Beijing, China.
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China. Electronic address: xiaoxiaohe302@126.com.
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
authors.affiliation: Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China. Electronic address: zhaoyl2855@126.com.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D002779:Cholestasis / Q000139:chemically induced / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D019254:Genes, bcl-2 / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects*; D039821:Monoterpenes / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D006027:Glycosides
chemical_list: D015058:1-Naphthylisothiocyanate; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D016207:Cytokines; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides
keywords: ANIT; Apoptosis; Cholestasis; Mitochondria signaling pathway; Peaoniflorin