Inhibitory effect of ginkgolide B on angiogenesis in chronic inflammation.
- Author:
Xue-yu OU-YANG
1
;
Wen-jie WANG
;
Wen-hui LIAO
;
Xiao-hong CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Line; Diterpenes; pharmacology; Female; Fibrinolytic Agents; pharmacology; Fibroblasts; cytology; metabolism; Ginkgolides; Granuloma; metabolism; pathology; Humans; Inflammation; metabolism; pathology; Interleukin-1; biosynthesis; genetics; Lactones; pharmacology; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; pathology; Platelet Activating Factor; antagonists & inhibitors; RNA, Messenger; biosynthesis; genetics; Tumor Necrosis Factor-alpha; biosynthesis; genetics; U937 Cells; metabolism
- From: Acta Pharmaceutica Sinica 2005;40(4):311-315
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the inhibitory effect of ginkgolide B on angiogenesis in chronic inflammation and the possible mechanisms.
METHODSThe murine chronic granulomatous air pouch model was used to observe the anti-angiogenesis effect of ginkgolide B. The vascular index was determined by colorimetry of carminic acid, and angiogenesis was observed by histology method. The interleukin-1beta (IL-1beta) levels in mice serum and in supernatants of U937 cell culture stimulated by phorbol 12-myristate 13-acetate (PMA) were detected by radioimmunoassay (RIA). The tumor necrosis factor-alpha (TNF-alpha) levels in mice serum and in supernatant of U937 cell culture were measured by cytotoxicity bioassay. The mRNA expression of IL-1beta and TNF-alpha of U937 cell culture was investigated by RT-PCR.
RESULTSOral administration of ginkgolide B 25 and 100 mg x kg(-1) was shown to significantly inhibit the vascular index of murine chronic granulomatous air pouch model with the inhibitory rate of 22.52% and 25.29%, respectively. This result was supported by histological observation. Concomitantly, the IL-1beta levels in mice serums were also significantly decreased with the inhibitory rate of 50.61% and 58.66%; so were the TNF-alpha levels with the inhibitory rate of 28.91% and 52.41%. Ginkgolide B at concentration of 1 x 10(-5) to 1 x 10(-8) mol x L(-1) could also reduce both the IL-1beta and TNF-alpha contents in the supernatants of U937 cell culture stimulated by PMA, but the scopes of changes were much different. For IL-1beta the IC50 was 1.93 x 10(-8) mol x L(-1), while ginkgolide B at concentration of 1 x 10(-5) mol x L(-1) only decreased the release of TNF-alpha by 25.99%. Furthermore, ginkgolide B at concentrations of 1 x 10(-5) to 1 x 10(-7) mol x L(-1) was shown to significantly inhibit TNF-alpha mRNA expression of U937 cells; and at concentrations of 1 x 10(-5) and 1 x 10(-6) mol x L(-1) could inhibit IL-1beta mRNA expression.
CONCLUSIONGinkgolide B was shown to significantly inhibit angiogenesis of the murine chronic granulomatous air pouch model, reduce the IL-1beta and TNF-alpha levels in mice serums, and significantly inhibit IL-1beta and TNF-alpha mRNA expression and protein secretion in supernatants of U937 cell culture. It was suggested that reduction of proangiogenic cytokines IL-1beta and TNF-alpha secretion may contribute to the anti-angiogenesis effect of ginkgolide B in the murine chronic granulomatous air pouch model.