Antiproliferative constituents isolated from Dendrobium nobile stem on hepatic stellate cells

Hepatic stellate cells have been known to play a key role in the pathogenesis of liver fibrosis [1]. In the course of screening for antifibrotic activity of natural products using HSC-T6, an immortalized rat hepatic stellate cell line as an in vitro assay system [2], the methanolic extract of Dendrobium nobile Lindl. stem (Orchidaceae) showed significant inhibitory activity on cell proliferation. Activity-guided fractionation resulted in the isolation of seven new phenanthrenes (1-7) along with twenty four known compounds (8-31). By spectroscopic analysis, the structures of compounds 1-7 were determined as 2,2'-dihydroxy-3,3',4,4',7,7'-hexamethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene (1), 3-hydroxy-2,4,7-trimethoxy-9,10-dihydrophenanthrene (2), 2,8-dihydroxy-3,4,7-trimethoxy-9,10-dihydrophenanthrene (3), 2-hydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene (4), 2,5-dihydroxy-3,4,8-trimethoxyphenanthrene (5), 2,8-dihydroxy-3,4,7-trimethoxyphenanthrene (6) and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene (7), respectively. Antifibrotic activity of compounds 1-31 was evaluated employing HSC-T6 cells by assessing cell proliferation. Among them, compounds 3, 7, denbinobin (12), fimbriol B (15), coelonin (21), 3-methylgigantol (23) and gigantol (24) significantly inhibited the proliferation of HSC-T6 cells (IC₅₀ values of 35.7, 9.0, 15.2, 11.0, 26.2, 34.8 and 25.5µM respectively).

Acknowledgements: Seoul R&BD Program (10541)

References: 1. Friedman, S. L. (1993) New Eng. J. Med. 328: 1828–1935.

2. Vogel, S. et al. (2000)J. Lipid. Res. 41: 882–893.