title: Spirodela polyrhiza extract modulates the activation of atopic dermatitis-related ion channels, Orai1 and TRPV3, and inhibits mast cell degranulation.
abstract: BACKGROUND
  Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash.
  
  
  OBJECTIVE
  The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated.
  
  
  METHODS
  The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100 μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100 μg/mL SH extract.
  
  
  RESULTS
  SH extract (100 μg/mL) significantly inhibited Orai1 activity (63.8 ± 0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29 ± 0.05% at -100 mV) compared with the positive control 2-APB (100 μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14 ± 0.03, 2.56 ± 0.12 and 2.29 ± 0.08 mU/mg, respectively).
  
  
  CONCLUSIONS
  Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.
authors.affiliation: a Department of Physiology , Dongguk University College of Medicine , Gyeongju , Republic of Korea.|b Channelopathy Research Center (CRC) , Dongguk University College of Medicine , Goyang , Gyeonggi-do , Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Nam
authors.affiliation: c College of Korean Medicine , Dongguk University , Gyeongju , Republic of Korea.
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Jung
authors.affiliation: d College of Pharmacy , Dongguk University , Goyang , Gyeonggi-do , Republic of Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.affiliation: e Department of Biochemistry , Dongguk University College of Medicine , Gyeongju , Republic of Korea.
authors.forename: Won-Mo
authors.initials: WM
authors.lastname: Yang
authors.affiliation: f Department of Sasang Constitutional Medicine , College of Korean Medicine, Dongguk University , Goyang , Gyeonggi-do , Republic of Korea.
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Bae
authors.affiliation: b Channelopathy Research Center (CRC) , Dongguk University College of Medicine , Goyang , Gyeonggi-do , Republic of Korea.|g Department of Internal Medicine, Graduate School of Medicine , Dongguk University , Goyang , Gyeonggi-do , Republic of Korea.
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Kim
mesh_terms: D029064:Araceae; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D000071740:ORAI1 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018408:Patch-Clamp Techniques / Q000379:methods; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000819:agonists* / Q000096:biosynthesis
chemical_list: D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D010936:Plant Extracts; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human
keywords: Atopic dermatitis; Orai1; Spirodela polyrhiza; Spirodelae Herba; TRPV3; calcium ion channels; mast cell degranulation