Immunosuppressive and Anti-Inflammatory Effects of Phenolic Nortriterpenoid, Demethylzeylasteral, from Tripterygium wilfordii

概要

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Demethylzeylasteral (Dzy), one of the 22 compounds isolated from a Chinese herbal medicine, Tripterygium wilfordii HOOK. 1, was examined for its immunosuppressive and anti-inflammatory activities. At 1,OOOnM (0.48μg/ml), Dzy inhibited the blastogenic responses of mouse spleen cells to T and B cell mitogens, the allogenic responses in mixed lymphocyte culture and the consumption of interleukin-2 (IL-2) by lymphocytes but hardly suppressed IL-2 production by lymphocytes, in contrast to cyclosporin A (CsA). When administered orally at a dose of 10 mg/kg Dzy significantly inhibited the delayed-type hypersensitivity in mice. Dzy strongly inhibited carrageenan-induced paw swelling in mice, but not the formation of plaque forming cells in mice at or above 3 mg/kg, and both primary and secondary inflammations in rat adjuvant arthritis at 3 and 10 mg/kg day. The rats treated with either Dzy or CsA in combination with prednisolone exhibited prolonged graft survivals of 60 days or longer, when the control rats rejected the graft. Moreover, combination therapy of Dzy and prednisolone was effective in suppressing ongoing rejection of cardiac graft, demonstrating strong immunosuppressive and anti-inflammatory activities of Dzy and suggesting a possible clinical use of Dzy as an immunosuppressive or anti- inflammatory agent in the fields of organ transplantation as well as autoimmune disorder.
日本生薬学会の論文
1997-04-20