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.
Yoshimura
Hiromitsu
H
Sugawara
Koko
K
Saito
Masako
M
Saito
Shiuji
S
Murakami
Shigeru
S
Miyata
Noriyuki
N
Kawashima
Akira
A
Morimoto
Shigeo
S
Gao
Nannan
N
Zhang
Xingguo
X
Yang
Junshan
J
D016475:3T3 Cells; D000818:Animals; D002681:China; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology; D019686:Lamiaceae / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D000097245:Ursolic Acid
D004365:Drugs, Chinese Herbal; D009828:Oleanolic Acid; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D000097245:Ursolic Acid; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse