4.4 Article

Oroxylin A, a classical natural product, shows a novel inhibitory effect on angiogenesis induced by lipopolysaccharide

Journal

PHARMACOLOGICAL REPORTS
Volume 64, Issue 5, Pages 1189-1199

Publisher

POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/S1734-1140(12)70915-5

Keywords

Scutellaria baicalensis Georgi (Lamiaceae); oroxylin A; lipopolysaccharide; angiogenesis; toll like receptor 4 (TLR4)

Funding

  1. National Natural Science Foundation of China [30973556, 81001452]
  2. Program for Changjiang Scholars and Innovative Research Team in University [IRT1193]
  3. Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGZ201101]
  4. National Science & Technology Major Project [2012ZX09304-001]
  5. Natural Science Foundation of Jiangsu province [BK2009297, BK2010432]

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Background: There is an obvious relationship among angiogenesis and inflammation. From previous study, we learn that oroxylin A possesses anti-angiogenic activity in vitro and in ovo. It also has an inhibitory effect on inflammation. But whether oroxylin A suppresses the inflammation-induced angiogenesis is still unknown. Our present study focuses on the role of oroxylin A in targeting LPS-induced angiogenesis, inflammatory and related pathways. Methods: The effects of oroxylin A on angiogenesis were investigated by transwell assay, tube formation assay, rat aortic ring assay and chorioallantoic membrane (CAM) model. Western blotting analysis was used to detect the expression of certain proteins. Results: We found that oroxylin A inhibited LPS-induced migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as microvessel sprouting from rat aotric ring in vitro and the angiogenesis of chicken chorioallantoic membrane (CAM) model in ovo. The results also indicated that oroxylin A could inhibit the expression of LPS acceptor toll-like receptor 4 (TLR4) and the activities of its downstream mitogen-activated protein kinases (MAPKs), including reducing expressions of the phosphorylation of INK, p38, and ERK. Moreover, oroxylin A prevented NF-kappa B dimers from translocating to the nucleus. Conclusions: Taken together, oroxylin A can suppress the angiogenesis induced by LPS and it may affect the LPS/TLR4 signaling pathway.

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