In vitro TGF-beta1 antagonistic activity of ursolic and oleanolic acids isolated from Clerodendranthus spicatus.

The mechanism of action of the aerial parts of Clerodendranthus spicatus (Thunb.) C.Y. Wu, [syn. Orthosiphon aristatus (Blume) Miq,] a medicinal plant used in China to treat human renal disease, was investigated. The aqueous and methanol crude extracts exhibited dose-dependent inhibitory activity on 125I-TGF-beta1 binding to its receptor in Balb/c 3T3 cells. Subsequent bioassay-guided fractionation led to identification of two known triterpenoidal constituents, ursolic and oleanolic acids. Ursolic and oleanolic acids inhibited the binding of 125I-TGF-beta1 to its receptor with IC 50 values of 6.9 +/- 0.8 and 21.0 +/- 2.3 microM, respectively. The results suggest that TGF-beta1 antagonistic activity is responsible, at least in part, for the therapeutic efficacy of this plant to treat humans with renal disease.