Inhibitory effect of magnosalin derived from Flos magnoliae on tube formation of rat vascular endothelial cells during the angiogenic process.
An aqueous water extract of Flos magnoliae, a Japanese Sino-medicine, inhibits angiogenesis in adjuvant-induced mouse pouch granuloma. Magnosalin (MSA) and magnoshinin (MSI), neolignans isolated from magnolia, have a crucial role in the anti-angiogenic effect of magnolia (Kimura et al., Int. Arch. Allergy Appl. Immunol., 93, 365 (1990); Phytother. Res., 6, 209 (1992)). We investigated the effects of these neolignans on tube formation of endothelial cells (EC) cultured in type I collagen gel during the angiogenic process. MSA (0.1-10 microM), MSI (0.23-7 microM) and corticosterone (CS: 0.3-30 microM) inhibited fetal bovine serum (FBS)-stimulated tube formation in a concentration-dependent manner. Their 30% inhibitory concentration (IC30, 95% confidence limits) values were 0.51 (0.20-1.27) for MSA, 8.14 (2.48-26.7) for MSI and 3.65 microM (2.47-5.40) for CS, respectively. MSA and MSI (1-3 microM) also inhibited interleukin (IL)-1 alpha-stimulated tube formation in a concentration-dependent manner. Their IC50 values (95% confidence limits) were 1.22 (1.01-1.47) for MSA and 0.74 microM (0.24-2.31) for MSI against a submaximal concentration (69 pM) of IL-1 alpha-stimulated tube formation. Their inhibitory effects on the action of IL-1 alpha were non-competitive. These results demonstrate that MSA inhibited FBS-stimulated tube formation with a greater potency than MSI. The inhibitory effect of MSA on the action of FBS differed from that on the action of IL-1 alpha.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
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Kobayashi
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Kimura
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Kimura
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003503:Cyclobutanes / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D017705:Lignans; D008031:Lignin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009284:Naphthols / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014197:Trees
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003503:Cyclobutanes; D007375:Interleukin-1; D017705:Lignans; D009284:Naphthols; C069674:magnosalin; C069675:magnoshinin; D008031:Lignin; D003345:Corticosterone