In vitro TGF-β1 Antagonistic Activity of Ursolic and Oleanolic Acids Isolated from Clerodendranthus spicatus

Abstract

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-β1 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-β1 to its receptor with IC₅₀ values of 6.9 ± 0.8 and 21.0 ± 2.3 μM, respectively. The results suggest that TGF-β1 antagonistic activity is responsible, at least in part, for the therapeutic efficacy of this plant to treat humans with renal disease.

References

• 1 Li H .-W. Some changes of botanical name in Chinese Labiatae.  Acta Phytotaxonomica Sinica. 1974;  12 213-34
• 2 Border W A, Noble N A. Cytokines in kidney disease: the role of transforming growth factor-beta.  American Journal of Kidney Disease. 1993;  22 105-13
• 3 Yamaguchi Y, Mann D M, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin.  Nature. 1990;  346 281-4
• 4 Doddrell D M, Khong P W, Lewis K G. The stereochemical dependence of ¹³C chemical shifts in olean-12-enes and urs-12-enes as an aid to structural assignment.  Tetrahedron Letters. 1974;  14 2381-5
• 5 Massague J. XXTitle of contribution? XX.  Methods in Enzymology. 1987;  146 174-95
• 6 Entzeroth M, Hadamovsky S. Angiotensin II receptors in the rat lung are of the AII-subtype.  European Journal of Pharmacology. 1991;  206 237-41
• 7 Williams L T, Tremble P M, Lavin M F, and Sunday M E. Platelet-derived growth factor receptors form a high affinity state in membrane preparations. Kinetics and affinity cross-linking studies.  Journal of Biological Chemistry. 1984;  259 5287-94
• 8 Wilkes L C, d Boarder M R. Characterization of the endothelin binding site on bovine adrenomedullary chromaffin cells: comparison with vascular smooth muscle cells. Evidence for receptor heterogeneity.  Journal of Pharmacology & Experimental Therapeutics. 1991;  256 628-33
• 9 Taga T, Kawanishi Y, Hardy R R, Hirano T, Kishimoto T. Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression.  Journal of Experimental Medicine. 1987;  166 967-81
• 10 Herbert J M, Bernat A, Valette G, Gigo V, Lale A, LaPlace M C, Lespy L, Savi P, Maffrand J P, Le Fur G J. Biochemical and pharmacological activities of SR 27 417, a highly potent, long-acting platelet-activating factor receptor antagonist.  Journal of Pharmacology & Experimental Therapeutics. 1991;  259 44-51
• 11 Brockhaus M, Schoenfeld H J, Schlaeger E J, Hunziker W, Lesslauer W, Loetscher H. Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies.  Proceedings of the National Academy of Sciences of USA. 1990;  87 3127-31
• 12 Higashiyama S, Abraham J A, Miller J, Fiddes J C, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF.  Science. 1991;  251 936-9
• 13 Winkler J D, Sarau H M, Foley J J, Mong S, Crooke S T. Leukotriene B4-induced homologous desensitization of calcium mobilization and phosphoinositide metabolism in U-937 cells.  Journal of Pharmacology & Experimental Therapeutics. 1988;  246 204-10