title: Inhibitory effects of tetrandrine on angiogenesis in adjuvant-induced chronic inflammation and tube formation of vascular endothelial cells.
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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Inaba
authors.forename: I
authors.initials: I
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kimura
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; C009438:tetrandrine