lignans and magnosalin

Two neolignans were isolated from leaves of Perilla frutescens (Labiatae) as inhibitors of nitric oxide syntheses (IC50 5.9 microM and 53.5 microM, respectively) and tumor necrosis factor-alpha in lipopolysaccharide-activated RAW 264.7 cells. Their structures were identified as 1beta,2alpha,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobutane (magnosalin), and 1alpha,2beta,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobutane (andamanicin), and their activities were confirmed as resulted from the suppressed expression of inducible nitric oxide synthase enzyme and from the secretion of tumor necrosis factor-alpha from activated macrophages.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cell Line; Cyclobutanes; Inhibitory Concentration 50; Lamiaceae; Lignans; Macrophages; Mice; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Plant Extracts; Tumor Necrosis Factor-alpha

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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cells, Cultured; Corticosterone; Cyclobutanes; Endothelium, Vascular; Interleukin-1; Lignans; Lignin; Male; Mice; Naphthols; Neovascularization, Physiologic; Rats; Rats, Wistar; Trees

Anti-proliferative effects of magnoshinin and magnosalin derived from "Shin-i" (Flos magnoliae) were investigated using subcultured endothelial cells (EC) of rat aorta. The inhibitory effects of magnoshinin were 2-fold greater at 10 micrograms/ml than that of magnosalin on the increase in cell number when EC were stimulated by 5% fetal bovine serum. In the 3H-thymidine incorporation monitored at 3 hr-intervals, magnoshinin (0.1-3 micrograms/ml) prolonged the starting time of DNA synthesis and reduced the rate of incorporation into EC. Magnosalin (0.3-3 micrograms/ml) reduced only the incorporation rate. These results suggest that magnoshinin inhibits both the competence phase and progression phase, but magnosalin preferentially inhibits the progression phase in EC proliferation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta, Thoracic; Cell Division; Cells, Cultured; Cyclobutanes; DNA; Endothelium, Vascular; Lignans; Male; Naphthols; Plants, Medicinal; Rats; Rats, Wistar

Inhibitory effects of magnosalin and magnoshinin, compounds from the crude drug "Shin-i" (Flos magnoliae), on angiogenesis and pouch granuloma formation in mice induced by an adjuvant containing croton oil were investigated. The anti-chronic inflammatory effect of "shin-i" was caused by selective inhibition of angiogenesis by magnosalin and of granuloma formation by magnoshinin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclobutanes; Freund's Adjuvant; Granuloma; Hydrocortisone; Lignans; Male; Mice; Mice, Inbred Strains; Naphthols; Neovascularization, Pathologic; Plants, Medicinal

Inhibitory effects of magnosalin and magnoshinin, compounds from the crude drug 'Shin-i' (Flos magnoliae), on angiogenesis and pouch granuloma formation induced by an adjuvant containing croton oil were investigated. Magnosalin inhibited angiogenesis 2.4-fold (intra-pouch) and 9.7-fold (intraperitoneal) more strongly than granuloma formation. The inhibition of angiogenesis by magnosalin was 5-fold (intra-pouch) and 21-fold (intraperitoneal) weaker than that by hydrocortisone. In contrast, intraperitoneal magnoshinin inhibited granuloma formation 2.5-fold more strongly than angiogenesis. The regression coefficients of anti-angiogenesis vs. the inhibition of granuloma formation were 1.79 for magnosalin, 1.11 for hydrocortisone, and 0.61 for magnoshinin. These results show that the anti-chronic inflammatory effect of 'Shin-i' was caused by selective inhibition of angiogenesis by magnosalin and of granuloma formation by magnoshinin.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclobutanes; Granuloma; Injections, Intraperitoneal; Lignans; Male; Mice; Naphthols; Neovascularization, Pathologic; Peritoneal Diseases; Peritoneum; Plants, Medicinal; Skin; Skin Diseases