Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway.

Autor:	Chen JF; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China., Liu F; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China., Qiao MM; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China., Shu HZ; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China., Li XC; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China., Peng C; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: pengcheng@cdutcm.edu.cn., Xiong L; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: xiling@cdutcm.edu.cn.
Jazyk:	angličtina
Zdroj:	Journal of ethnopharmacology [J Ethnopharmacol] 2022 Aug 10; Vol. 294, pp. 115332. Date of Electronic Publication: 2022 May 05.
DOI:	10.1016/j.jep.2022.115332
Abstrakt:	Ethnopharmacological Relevance: Curcuma longa L. (Zingiberaceae) is a known blood-activating and stasis-removing traditional Chinese medicine and has relevant pharmacological properties. The rhizomes of C. longa have been used for the treatment of cardiovascular disease (CVD) in China. Previous studies have shown that sesquiterpenoids from C. longa have significant vasorelaxant effects, which are closely associated with the prevention and treatment of CVD. Aim of the Study: To explore the sesquiterpenoids with vasorelaxant effects from C. longa and investigate the underlying mechanisms. Materials and Methods: The compound was isolated from C. longa by multiple chromatography technologies. Its structure was determined by extensive spectroscopic analyses, nuclear magnetic resonance (NMR) data calculations, electronic circular dichroism (ECD) data calculations, and optical rotation (OR) data calculations. The vasorelaxant effect of the isolated compound was evaluated by KCl- or phenylephrine (PHE)-inducing contraction of the rat thoracic aortic rings. Endothelial removal and L-NAME pretreatment experiments were used to verify the endothelium-dependent vasorelaxant effect of the isolated compound in rat thoracic aortic rings. NO production was monitored in human umbilical vein endothelial cells (HUVECs). Western blot was carried out in HUVECs to elucidate the potential mechanisms. Results: A new bisabolane-type sesquiterpenoid, curcubisabolanin A [(+)-(1S,7S,9E)-bisabola-2(3),4(15),9(10)-trien-11-ol], was isolated from the rhizomes of C. longa. curcubisabolanin A exhibited endothelium-dependent relaxation on rat thoracic aortic rings, while pre-treatment of intact aortic rings with an eNOS inhibitor (L-NAME) attenuated the vasorelaxant response of curcubisabolanin A. In addition, curcubisabolanin A induced intracellular NO production and significantly increased the levels of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), and phosphorylated eNOS (p-eNOS) in HUVECs. LY294002 (a blocker of PI3K) and MK-2206 (a highly selective inhibitor of Akt) significantly decreased these effects of curcubisabolanin A. Conclusions: These findings demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent and was related to regulation of NO production in vascular endothelial cells through the PI3K/Akt/eNOS signaling pathway. (Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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