title: Quercetin is a Useful Medicinal Compound Showing Various Actions Including Control of Blood Pressure, Neurite Elongation and Epithelial Ion Transport.
abstract: Quercetin has multiple potential to control various cell function keeping our body condition healthy. In this review article, we describe the molecular mechanism on how quercetin exerts its action on blood pressure, neurite elongation and epithelial ion transport based from a viewpoint of cytosolic Cl- environments, which is recently recognized as an important signaling factor in various types of cells. Recent studies show various roles of cytosolic Cl- in regulation of blood pressure and neurite elongation, and prevention from bacterial and viral infection. We have found the stimulatory action of quercetin on Cl- transporter, Na+-K+-2Cl- cotransporter 1 (NKCC1; an isoform of NKCC), which has been recognized as one of the most interesting, fundamental actions of quercetin. In this review article, based on this stimulatory action of quercetin on NKCC1, we introduce the molecular mechanism of quercetin on: 1) blood pressure, 2) neurite elongation, and 3) epithelial Cl- secretion including tight junction forming in epithelial tissues. 1) Quercetin induces elevation of the cytosolic Cl- concentration via activation of NKCC1, leading to anti-hypertensive action by diminishing expression of epithelial Na+ channel (ENaC), a key ion channel involved in renal Na+ reabsorption, while quercetin has no effects on the blood pressure with normal salt intake. 2) Quercetin also has stimulatory effects on neurite elongation by elevating the cytosolic Cl- concentration via activation of NKCC1 due to tubulin polymerization facilitated through Cl--induced inhibition of GTPase. 3) Further, in lung airway epithelia quercetin stimulates Cl- secretion by increasing the driving force for Cl- secretion via elevation of the cytosolic Cl- concentration: this leads to water secretion, participating in prevention of our body from bacterial and viral infection. In addition to transcellular ion transport, quercetin regulates tight junction function via enhancement of tight junction integrity by modulating expression and assembling tight junction-forming proteins. Based on these observations, it is concluded that quercetin is a useful medicinal compound keeping our body to be in healthy condition.
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto 602-8013, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto 602-8013, Japan.|Department of Health and Sports Sciences, Faculty of Health and Medical Sciences, Kyoto Gakuen University, Kameoka 621-8555, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Niisato
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto 602-8013, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nakajima
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Taruno
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Marunaka
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Okui
authors.affiliation: Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Narisato
authors.initials: N
authors.lastname: Kanamura
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Kogiso
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ikeuchi
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kashio
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto 602-8013, Japan.
authors.forename: Shigekuni
authors.initials: S
authors.lastname: Hosogi
authors.affiliation: Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto 602-8013, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001424:Bacterial Infections / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects*; D001834:Body Water / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects; D014777:Virus Diseases / Q000517:prevention & control
chemical_list: D000975:Antioxidants; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D011794:Quercetin
keywords: Cl-; ENaC; Flavonoid; GTPase; Na+-K+-2Cl- cotransporter; neurite; tubulin.