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      Actions of Quercetin, a Polyphenol, on Blood Pressure

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          Abstract

          Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the values of various blood pressure regulatory factors, such as vascular compliance, peripheral vascular resistance, and total blood volume via anti-inflammatory and anti-oxidant actions. In addition to the anti-inflammatory and anti-oxidant actions of quercetin, we especially describe a novel mechanism of quercetin’s action on the cytosolic Cl concentration ([Cl ] c) and novel roles of the cytosolic Cl i.e., (1) quercetin elevates [Cl ] c by activating Na +-K +-2Cl cotransporter 1 (NKCC1) in renal epithelial cells contributing to Na + reabsorption via the epithelial Na + channel (ENaC); (2) the quercetin-induced elevation of [Cl ] c in renal epithelial cells diminishes expression of ENaC leading to a decrease in renal Na + reabsorption; and (3) this reduction of ENaC-mediated Na + reabsorption in renal epithelial cells drops volume-dependent elevated blood pressure. In this review, we introduce novel, unique mechanisms of quercetin’s anti-hypertensive action via activation of NKCC1 in detail.

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          Most cited references75

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          Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.

          The amiloride-sensitive epithelial sodium channel constitutes the rate-limiting step for sodium reabsorption in epithelial cells that line the distal part of the renal tubule, the distal colon, the duct of several exocrine glands, and the lung. The activity of this channel is upregulated by vasopressin and aldosterone, hormones involved in the maintenance of sodium balance, blood volume and blood pressure. We have identified the primary structure of the alpha-subunit of the rat epithelial sodium channel by expression cloning in Xenopus laevis oocytes. An identical subunit has recently been reported. Here we identify two other subunits (beta and gamma) by functional complementation of the alpha-subunit of the rat epithelial Na+ channel. The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.
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            Review of the biology of quercetin and related bioflavonoids

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              Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase.

              Lactase phlorizin hydrolase (LPH; EC 3.2.1.62) is a membrane-bound, family 1 beta-glycosidase found on the brush border of the mammalian small intestine. LPH, purified from sheep small intestine, was capable of hydrolysing a range of flavonol and isoflavone glycosides. The catalytic efficiency (k(cat)/K(m)) for the hydrolysis of quercetin-4'-glucoside, quercetin-3-glucoside, genistein-7-glucoside and daidzein-7-glucoside was 170, 137, 77 and 14 (mM(-1) s(-1)) respectively. The majority of the activity occurred at the lactase and not phlorizin hydrolase site. The ability of LPH to deglycosylate dietary (iso)flavonoid glycosides suggests a possible role for this enzyme in the metabolism of these biologically active compounds.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                29 January 2017
                February 2017
                : 22
                : 2
                : 209
                Affiliations
                [1 ]Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; marurie@ 123456koto.kpu-m.ac.jp (R.M.); crystal@ 123456koto.kpu-m.ac.jp (H.S.); inui-cl@ 123456nike.eonet.ne.jp (T.I.); taruno@ 123456koto.kpu-m.ac.jp (A.T.)
                [2 ]Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
                [3 ]Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto 602-8013, Japan
                [4 ]Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; yamamoto@ 123456koto.kpu-m.ac.jp (T.Y.); kanamura@ 123456koto.kpu-m.ac.jp (N.K.)
                [5 ]Saisei Mirai Clinics, Moriguchi 570-0012, Japan
                Author notes
                [* ]Correspondence: marunaka@ 123456koto.kpu-m.ac.jp ; Tel.: +81-75-251-5310
                Article
                molecules-22-00209
                10.3390/molecules22020209
                6155806
                28146071
                410b1b60-b48b-4d82-a8f5-b4b1448ee3d5
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 December 2016
                : 24 January 2017
                Categories
                Review

                flavonoid,quercetin,na+-k+-2cl− cotransporter 1,epithelial na+ channel,cytosolic cl− concentration

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