title: Rumex acetosa L. induces vasorelaxation in rat aorta via activation of PI3-kinase/Akt- AND Ca(2+)-eNOS-NO signaling in endothelial cells.
abstract: Rumex acetosa L. (RA) (Polygonaceae) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China and the aerial parts of RA has a wide variety of pharmacological actions such as diuretic, anti-hypertensive, anti-oxidative, and anti-cancer effects. However, the mechanisms involved are to be defined. The purpose of the present study was to evaluate the vasorelaxant effect and define the mechanism of action of the ethanol extract of Rumex acetosa L. (ERA) in rat aorta. ERA was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aorta and its acute effects on arterial blood pressure. In addition, the roles of the nitric oxide synthase (NOS)-nitric oxide (NO) signaling in the ERA-induced effects were tested in human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of Akt and eNOS were assessed by Western blot analysis in the cultured HUVECs. ERA induced endothelium-dependent vasorelaxation. The ERA-induced vasorelaxation was abolished by L-NAME (an NOS inhibitor) or ODQ (a sGC inhibitor), but not by indomethacin. Inhibition of PI3-kinase/Akt signaling pathway markedly reduced the ERA-induced vasorelaxation. In HUVECs, ERA increased NO formation in a dose-dependent manner, which was inhibited by L-NAME and by removing extracellular Ca(2+). In addition, ERA promoted phosphorylation of Akt and eNOS, which was prevented by wortmannin and LY294002, indicating that ERA induces eNOS phosphorylation through the PI3-kinase/Akt pathway. Further, in anesthetized rats, intravenously administered ERA decreased arterial blood pressure in a dose-dependent manner through an activation of the NOS-NO system. In summary, the ERA- induced vasorelaxation was dependent on endothelial integrity and NO production, and was mediated by activation of both the endothelial PI3-kinase/Akt- and Ca(2+)-eNOS-NO signaling and muscular NO-sGC-cGMP signaling.
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Su
authors.affiliation: Department of Pharmacology, Qingdao University Medical School, Qingdao, Shandong, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, China.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, China.
authors.forename: S S
authors.initials: SS
authors.lastname: Sun
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, Taishan Medical University, Taian, Shandong, China. jfwen0603@aliyun.com.
authors.forename: J F
authors.initials: JF
authors.lastname: Wen
authors.affiliation: Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Korea.
authors.forename: D G
authors.initials: DG
authors.lastname: Kang
authors.affiliation: Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, Taishan Medical University, Taian, Shandong, China.
authors.forename: K W
authors.initials: KW
authors.lastname: Cho
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, China. snjin0504@aliyun.com.
authors.forename: S N
authors.initials: SN
authors.lastname: Jin
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008516:Medicine, Chinese Traditional; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D031804:Rumex; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP; D002118:Calcium