NDLI: Chinese medicine Tongxinluo modulates vascular endothelial function by inducing eNOS expression via the PI-3K/Akt/HIF-dependent signaling pathway.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Liang, Jun Qing Wu, Kun Jia, Zhen Hua Liu, Chang Ding, Jin Huang, Shan Na Yin, Pei Pei Wu, Xiang Chun Wei, Cong Wu, Yi Ling Wang, Hong Yang
Spatial Coverage	China
Description	Country affiliation: China Author Affiliation: Liang JQ ( The International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.)
Abstract	AIM OF THE STUDY: To investigate the molecular mechanisms whereby the Chinese medicinal compound Tongxinluo improves vascular endothelial function through studying the induction of endothelial nitric oxide synthase (eNOS) and its upstream signaling pathway. MATERIALS AND METHODS: Hyperhomocysteinemia was induced in Wistar rats by a methionine-rich diet followed by Tongxinluo treatment. The aorta ring was isolated for measuring vascular dilation of aorta and eNOS expression. Human umbilical vein endothelial cells (HUVECs) were transfected with AP-1, NF-κB, HRE or eNOS reporter plasmid followed by Tongxinluo exposure. Expression of the reporter genes was measured by luciferase assay. The level of eNOS was studied by western blot and the nitric oxide content was measured using the nitrate reductase method. HUVECs were also transiently transfected with the dominant negative mutant of HIF-1, PI-3K or Akt to explore the role of HIF and PI-3K/Akt pathway in eNOS induction by Tongxinluo. RESULTS: Tongxinluo could significantly up-regulate the expression of eNOS in the aortic tissue and improve the endothelium-dependent vasodilation of the aorta ring. Additionally, Tongxinluo at various doses could significantly enhance the expression of HRE and eNOS reporter gene as well as up-regulate the protein level of eNOS. Meanwhile, Tongxinluo caused a dose-dependent increase in the NO content in the supernatant of HUVECs. Suppression of HIF-1 activation by DN-HIF or inhibition of PI-3K/Akt pathway by ΔP85 or DN-Akt both attenuated HRE reporter gene activation and eNOS induction by Tongxinluo. CONCLUSION: Tongxinluo, a compound Chinese traditional medicine, up-regulates the expression of eNOS via the PI-3K/Akt/HIF-dependent signaling pathway, thus improving the endothelium-dependent vasodilation.
File Format	HTM / HTML
ISSN	03788741
Issue Number	2
Volume Number	133
e-ISSN	18727573
Journal	Journal of Ethnopharmacology
Language	English
Publisher	Elsevier
Publisher Date	2011-01-27
Publisher Place	Ireland
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Ethnopharmacology Drugs, Chinese Herbal Pharmacology Endothelium, Vascular Drug Effects Physiology Hypoxia-inducible Factor 1 Metabolism Nitric Oxide Synthase Type Iii Phosphatidylinositol 3-kinases Proto-oncogene Proteins C-akt Animals Aorta, Thoracic Cells, Cultured China Ethnopharmacology Genes, Reporter Humans Genetics In Vitro Techniques Male Medicine, Chinese Traditional Rats Rats, Wistar Signal Transduction Transfection Up-regulation Vasodilation Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmacology

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