25-OCH₃-PPD induces the apoptosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-¦ÊB activation

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• 作者：Yan-ling  ; Wu^a ;   ; ¹ ; Ying  ; Wan^a ;   ; ¹ ; Xue-Jun  ; Jin^a ; Bing-Qing  ; OuYang^a ; Ting  ; Bai^a ; Yu-Qing  ; Zhao^b ;   ; ^{zyq4885@126.com} ; Ji-Xing  ; Nan^a ;   ; ^{jxnanybu@gmail.com}
• 关键词：25-OCH₃-PPD ; Anti-fibrosis ; Apoptosis ; c-FLIP ; NF-¦ÊB
• 刊名：Chemico-Biological Interactions
• 出版年：2011
• 出版时间：15 November 2011
• 年：2011
• 卷：194
• 期：2-3
• 页码：106-112
• 全文大小：863 K

文摘

25-OCH₃-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-OCH₃-PPD on apoptosis of activated t-HSC/Cl-6 cells induced by tumor necrosis factor-¦Á (TNF-¦Á). The inhibitory effects of eleven compounds isolated from Panax ginseng and P. notoginseng were detected in activated t-HSC/Cl-6 cells. 25-OCH₃-PPD produced a significant inhibitory effect on activated t-HSC/Cl-6 cells. However, 25-OCH₃-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-OCH₃-PPD and to characterize the signal transduction pathways involved in activated HSCs. 25-OCH₃-PPD decreased the fibrosis markers, including ¦Á-smooth muscle actin (¦Á-SMA), transforming growth factor ¦Â-1 (TGF-¦Â1) and tissue inhibitors of metalloproteinases-1 (TIMP-1). 25-OCH₃-PPD elevated the level of cellular GSH in activated HSCs, which demonstrated that 25-OCH₃-PPD might inhibit HSC activation by its antioxidant capacity. Further analyses revealed that 25-OCH₃-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-¦ÊB activation and shed light on the regulation of apoptosis. Therefore, 25-OCH₃-PPD may prove to be an excellent candidate agent for the therapy of hepatic fibrosis.