1. Dehydroabietic acid isolated from Commiphora opobalsamum causes endothelium-dependent relaxation of pulmonary artery via PI3K/Akt-eNOS signaling pathway.
- Author
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Gao W, Dong X, Xie N, Zhou C, Fan Y, Chen G, Wang Y, Wei T, and Zhu D
- Subjects
- Abietanes chemistry, Animals, Cells, Cultured, Chromones pharmacology, Commiphora metabolism, Diterpenes chemistry, Drug Evaluation, Preclinical, Endothelial Cells physiology, Enzyme Inhibitors pharmacology, Male, Medicine, Chinese Traditional, Morpholines pharmacology, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type III metabolism, Phosphatidylinositol 3-Kinase metabolism, Proto-Oncogene Proteins c-akt metabolism, Pulmonary Artery cytology, Rats, Rats, Wistar, Signal Transduction drug effects, Abietanes pharmacology, Diterpenes pharmacology, Phosphoinositide-3 Kinase Inhibitors, Pulmonary Artery physiology, Vasodilation drug effects
- Abstract
Commiphora opobalsamum is a Traditional Chinese Medicine used to treat traumatic injury, mainly by relaxing blood vessels. In this study, two diterpenes, dehydroabietic acid (DA) and sandaracopimaric acid (SA) were obtained from it by a bioassay-guided approach using isolated rat pulmonary artery rings. The structures of the two compounds were elucidated by spectroscopic methods (IR, 1H- and 13C-NMR, HR-ESI-MS). Both DA and SA reduced the contraction of phenylephrine-induced pulmonary arteries in a concentration-dependent manner, and endothelium contributed greatly to the vasodilatory effect of DA. This effect of DA was attenuated by NG-Nitro-L-arginine methyl ester (L-NAME, an eNOS inhibitor). Meanwhile, DA increased nitric oxide (NO) production, along with the increase of phosphorylation level of eNOS and Akt in endothelial cells. LY294002 (a PI3K inhibitor) could reverse this effect, which suggested the endothelial PI3K/Akt pathway involved in the mechanism underlying DA-induced relaxation of pulmonary artery. This work provided evidence of vasorelaxant substances in Commiphora opobalsamum and validated that PI3K/Akt-eNOS pathway was associated with DA-induced pulmonary artery vasodilation.
- Published
- 2014
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