Abstract
The inhibitory effects of tetrandrine (an alkaloid isolated from the Chinese medicine Stephania tetrandrae S. Moore) were investigated in terms of the angiogenesis in an adjuvant-induced chronic inflammation model of mouse and tube formation of rat vascular endothelial cells (EC). Tetrandrine (7.5-30 mg/kg) reduced the carmine content, granuloma weight, inflammatory cell count and pouch fluid weight in the inflammation model in a dose-dependent manner. The inhibitory pattern of tetrandrine on these parameters was similar to that of hydrocortisone. The inhibitory effect of tetrandrine on carmine content was 0.56-fold smaller than that of hydrocortisone. Tetrandrine (0.1-10 microM) also inhibited 2% fetal bovine serum (FBS)-stimulated tube formation of vascular EC. The inhibitory effect of tetrandrine on tube formation was more than 100-fold greater than that of hydrocortisone. Tetrandrine (10-30 nM) inhibited the tube formation stimulated by interleukin (IL)-1alpha and platelet-derived growth factor (PDGF)-BB to a greater extent than FBS-stimulated tube formation. The inhibitory effects of tetrandrine on the action of IL-1alpha and PDGF-BB were non-competitive. These results demonstrate that tetrandrine may reduce the tube formation of EC in the angiogenic process through inhibition on the post-receptor pathway of IL-1alpha and PDGF-BB in chronic inflammation.
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