Anti-angiogenic activity of Ipomoea obscura extract and Ipobscurine-A.

Abstract:

OBJECTIVE:Ipomoea obscura (L.) Ker-Gawl, is a medicinal herb with indole alkaloids as an active constituent. In this study, we investigated the anti-angiogenic activity of I. obscura extract and one of its major compounds Ipobscurine-A (IPO-A). METHODS:In vivo angiogenesis was induced by injecting B16F10 melanoma cells intradermally on the shaven ventral skin of C57BL/6 mice. In vitro experiments were conducted using human umbilical vein endothelial cells. RESULTS:I. obscura and IPO-A significantly inhibited endothelial cell proliferation, migration, invasion, and tube formation in vitro. Vascular endothelial growth factor (VEGF)-induced sprouting of endothelial cells from rat aorta ex vivo was also inhibited. A marked decrease in the production of matrix metalloproteinases (MMPs) and the expressions of VEGF, cyclooxygenase-2, and nitric oxide synthase by B16F10 cells were observed after the treatment with the extract or IPO-A. Intraperitoneal administration of the extract significantly inhibited B16F10 melanoma cell line-induced neo-vessel formation in C57BL/6 mice in vivo. Analysis of serum cytokine profile clearly showed that extract significantly reduced the elevated levels of pro-inflammatory cytokines such as interleukins (IL)-1β, IL-6, tumor necrosis factor-α, and granulocyte-monocyte colony stimulating factor and the most potent angiogenic factor VEGF in animals. Serum NO level was also found to be significantly lowered by the administration of the extract. Anti-angiogenic factors such as TIMP-1 and IL-2 level were elevated in the extract-treated animals. CONCLUSION:These data clearly demonstrate that I. obscura extract and IPO-A inhibit the tumor-specific angiogenesis by downregulating pro-angiogenic factors such as MMP, VEGF, and pro-inflammatory mediators and upregulating anti-angiogenic factors such as IL-2 and TIMP-1.

authors

Hamsa TP,Kuttan G

doi

10.3109/08923973.2010.531277

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

488-97

issue

3

eissn

0892-3973

issn

1532-2513

journal_volume

33

pub_type

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