title: 25-OCH3-PPD induces the apoptosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-κB activation.
abstract: 25-OCH(3)-PPD is a dammarane-type triterpene sapogenin isolated from the roots, leaves and seeds of Panax notoginseng, which has shown anti-tumor effects in several human cancer lines. In this study, we evaluated the effects of 25-OCH(3)-PPD on apoptosis of activated t-HSC/Cl-6 cells induced by tumor necrosis factor-α (TNF-α). The inhibitory effects of eleven compounds isolated from Panax ginseng and P. notoginseng were detected in activated t-HSC/Cl-6 cells. 25-OCH(3)-PPD produced a significant inhibitory effect on activated t-HSC/Cl-6 cells. However, 25-OCH(3)-PPD showed almost no effect on the cell viability of Chang liver cells, a type of normal human hepatic cell line. Therefore, we aimed to determine the anti-fibrotic potential of 25-OCH(3)-PPD and to characterize the signal transduction pathways involved in activated HSCs. 25-OCH(3)-PPD decreased the fibrosis markers, including α-smooth muscle actin (α-SMA), transforming growth factor β-1 (TGF-β1) and tissue inhibitors of metalloproteinases-1 (TIMP-1). 25-OCH(3)-PPD elevated the level of cellular GSH in activated HSCs, which demonstrated that 25-OCH(3)-PPD might inhibit HSC activation by its antioxidant capacity. Further analyses revealed that 25-OCH(3)-PPD increased the levels of cleaved caspase-3, decreased the ratio of Bcl-2/Bax and the expression of survivin via c-FLIP-mediated NF-κB activation and shed light on the regulation of apoptosis. Therefore, 25-OCH(3)-PPD may prove to be an excellent candidate agent for the therapy of hepatic fibrosis.
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province, China.
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Jin
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: OuYang
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Zhao
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000502:physiology*; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012502:Sapogenins / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D016328:NF-kappa B; D012502:Sapogenins; D005978:Glutathione