Inhibitory effects of tetrandrine on angiogenesis in adjuvant-induced chronic inflammation and tube formation of vascular endothelial cells.
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.
Kobayashi
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Inaba
K
K
Kimura
I
I
Kimura
M
M
D000276:Adjuvants, Immunologic / Q000633:toxicity; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006099:Granuloma / Q000188:drug therapy / Q000473:pathology; D015745:Granuloma, Foreign-Body / Q000473:pathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats
D000276:Adjuvants, Immunologic; D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; C009438:tetrandrine