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25-OCH3-PPD is a dammarane-type triterpene sapogenin isolated from the roots, leaves and seeds of P.notoginseng, which has shown anti-tumor effects in several human cancer lines.The effects of 25-OCH3-PPD on apoptosis of activated t-HSC/Cl-6 cells induced by tumor necrosis factor-α (TNF-α) were evaluated.The inhibitory effects of eleven compounds isolated from P.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 ceils, a type of normal human heparic 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 α-smooth muscle actin (α-SMA), transforming growth factor β-1 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-κB 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.