[Inhibitory effect of ginkgolide B on angiogenesis in chronic inflammation].

Abstract

AIM:

To investigate the inhibitory effect of ginkgolide B on angiogenesis in chronic inflammation and the possible mechanisms.

METHODS:

The 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.

RESULTS:

Oral 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.

CONCLUSION:

Ginkgolide 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.

• Authors: Xue-yu Ou-Yang, Wen-jie Wang, Wen-hui Liao, Xiao-hong Chen
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 40 Issue 4 Pg. 311-5 (Apr 2005) ISSN: 0513-4870 [Print] China
• PMID: 16011257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Fibrinolytic Agents
• Ginkgolides
• Interleukin-1
• Lactones
• Platelet Activating Factor
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• ginkgolide B

Topics

• 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)