Prevention of secretory diarrhea by ethanol extract of <i>Bistortae rhizoma</i> through inhibition of chloride channel

  • Bo Yu Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041 http://orcid.org/0000-0002-5976-6364
  • Yu Jiang School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029
  • Yue Liu School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029
  • Tonghui Ma Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041; College of Basic Medical Sciences, Dalian Medical University, Dalian 116044
  • Hong Yang School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029
Keywords: Bistortae Rhizoma, Chloride channel, Diarrhea

Abstract

Inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) and Ca2+-activated Cl- channel (CaCC) represents an attractive approach for the treatment of secretory diarrhea. The aim of the study is to investigate the molecular basis of the anti-diarrheal effect of traditional Chinese herbal anti-diarrheal medicine Bistortae rhizoma. Fluorescence quenching assay indicated that the 40% methanol /water fraction (D5) dose-dependently inhibited both CFTR and CaCC function in transfected Fischer rat thyroid (FRT) cells. Ex vivo studies indicated that D5 inhibited both forskolin (FSK)-activated CFTR current and CCh-induced CaCC current in rat colonic mucosa. In the mouse closed-loop model, intraluminal application of D5 (200 µg/mL) significantly reduced cholera toxin-stimulated fluid secretion. In the intestinal motility model, D5 significantly delayed intestinal peristalsis in mice. Our research suggests that CFTR and CaCC-mediated intestinal epithelial Cl- secretion inhibiting and gastrointestinal motility delaying may account for the anti-diarrheal activity of B. rhizoma.  

 

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References

Berschneider HM, Knowles MR, Azizkhan RG, Boucher RC, Tobey NA, Orlando RC, Powell DW. Altered intestinal chloride transport in cystic fibrosis. FASEB J. 1988; 2: 2625-29.

Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 2008; 322: 590-94.

Chao AC, de Sauvage FJ, Dong YJ, Wagner JA, Goeddel DV, Gardner P. Activation of intestinal CFTR Cl-channel by heat-stable enterotoxin and guanylin via cAMP-dependent protein kinase. EMBO J. 1994; 13: 1065-72.

Chen L, Yu B, Zhang Y, Gao X, Zhu L, Ma T, Yang H. Bioactivity-guided fractionation of an anti-diarrheal Chinese herb Rhodiola kirilowii (Regel) Maxim reveals (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate as inhibitors of cystic fibrosis transmembrane conductance regulator. PLoS One. 2015; 10: e0119122.

Clarke LL, Stien X, Walker NM. Intestinal bicarbonate secretion in cystic fibrosis mice. JOP. 2001; 2(4 Suppl): 263-67.

Ferrera L, Caputo A, Galietta LJ. TMEM16A protein: A new identity for Ca2+-dependent Cl- channels. Physiology (Bethesda). 2010; 25: 357-63.

Grubb BR. Ion transport across the jejunum in normal and cystic fibrosis mice. Am J Physiol. 1995; 268: G50513.

Hao F, Yi F, Zhang D, Ning Y, Su W, Feng X, Yang H, Ma T. Identification of herbal compound imperatorin with adverse effects on ANO1 and CFTR chloride channels. Chem Res Chinese U. 2011; 27: 461-63.

Harmon GS, Dumlao DS, Ng DT, Barrett KE, Dennis EA, Dong H, Glass CK. Pharmacological correction of a defect in PPAR-gamma signaling ameliorates disease severity in CFTR-deficient mice. Nat Med. 2010; 16: 313-18.

He C, Zhang H, Su Z, Zhou J, Yang H. Synthesis and characterization of a small molecule CFTR chloride channel inhibitor. Chem Res Chinese U. 2004; 20: 334-37.

Huang F, Rock JR, Harfe BD, Cheng T, Huang X, Jan YN, Jan LY. Studies on expression and function of the TMEM16A calcium-activated chloride channel. Proc Natl Acad Sci USA. 2009; 106: 21413-18.

Hwang SJ, Blair PJ, Britton FC, O'Driscoll KE, Hennig G, Bayguinov YR, Rock JR, Harfe BD, Sanders KM, Ward SM. Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol. 2009; 587: 4887-904.

Istrate C, Hagbom M, Vikström E, Magnusson KE, Svensson L. Rotavirus infection increases intestinal motility but not permeability at the onset of diarrhea. J Virol. 2014; 88: 3161-69.

Jiang M, Yang J, Zhang, C, Liu B, Chan K, Cao H, Lu A. Clinical studies with traditional Chinese medicine in the past decade and future research and development. Planta Med. 2010; 76: 2048-64.

Li T, Peng T. Traditional Chinese herbal medicine as a source of molecules with antiviral activity. Antiviral Res. 2013; 97: 1-9.

Morris AP, Scott JK, Ball JM, Zeng CQ, O'Neal WK, Estes MK. NSP4 elicits age-dependent diarrhea and Ca2+ mediated I influx into intestinal crypts of CF mice. Am J Physiol. 1999; 277: G431-44.

Namkung W, Thiagarajah JR, Phuan PW, Verkman AS. Inhibition of Ca2+-activated Cl channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. FASEB J. 2010; 24: 4178-86.

National Pharmacopoeia Committee. Pharmacopoeia of Peoples Republic of China. Vol. 1. Beijing, China Medical Science and Technology Press, 2005.

O'Loughlin EV, Hunt DM, Gaskin KJ, Stiel D, Bruzuszcak IM, Martin HC, Bambach C, Smith R. Abnormal epithelial transport in cystic fibrosis jejunum. Am J Physiol. 1991; 260: G758-63.

Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, et al. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1989; 245: 1066-73.

Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM. Anoctamins and gastrointestinal smooth muscle excitability. Exp Physiol. 2012; 97: 200-06.

Schroeder BC, Cheng T, Jan YN, Jan LY. Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 2008; 134: 1019-29.

Sonawane ND, Zhao D, Zegarra-Moran O, Galietta LJ, Verkman AS. Lectin conjugates as potent, nonabsorbable CFTR inhibitors for reducing intestinal fluid secretion in cholera. Gastroenterology 2007; 132: 1234-44.

Thiagarajah JR, Broadbent T, Hsieh E, Verkman AS. Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology 2004; 126: 511-19.

Published
2015-07-01
How to Cite
Yu, B., Jiang, Y., Liu, Y., Ma, T., & Yang, H. (2015). Prevention of secretory diarrhea by ethanol extract of <i>Bistortae rhizoma</i&gt; through inhibition of chloride channel. Bangladesh Journal of Pharmacology, 10(3), 533-542. https://doi.org/10.3329/bjp.v10i3.23260
Section
Research Articles