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Cucumis sativus extract elicits chloride secretion by stimulation of the intestinal TMEM16A ion channel.
Saha, Tultul; Aoun, Joydeep; Sarkar, Paramita; Bourdelais, Andrea J; Baden, Daniel G; Leblanc, Normand; Hamlyn, John M; Woodward, Owen M; Hoque, Kazi Mirajul.
Affiliation
  • Saha T; Pathophysiology Division, National Institute of Cholera & Enteric Diseases, Kolkata, India.
  • Aoun J; Pathophysiology Division, National Institute of Cholera & Enteric Diseases, Kolkata, India.
  • Sarkar P; Department of Pharmacology, The Center for Cardiovascular Research, Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, NV, USA.
  • Bourdelais AJ; Pathophysiology Division, National Institute of Cholera & Enteric Diseases, Kolkata, India.
  • Baden DG; Center for Marine Science, University of North Carolina, Wilmington, NC, USA.
  • Leblanc N; Center for Marine Science, University of North Carolina, Wilmington, NC, USA.
  • Hamlyn JM; Department of Pharmacology, The Center for Cardiovascular Research, Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, NV, USA.
  • Woodward OM; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Hoque KM; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Pharm Biol ; 59(1): 1008-1015, 2021 Dec.
Article de En | MEDLINE | ID: mdl-34362288
ABSTRACT
CONTEXT Cucumber (Cucumis sativus Linn. [Cucurbitaceae]) is widely known for its purgative, antidiabetic, antioxidant, and anticancer therapeutic potential. However, its effect on gastrointestinal (GI) disease is unrecognised.

OBJECTIVE:

This study investigated the effect of C. sativus fruit extract (CCE) on intestinal chloride secretion, motility, and motor function, and the role of TMEM16A chloride channels. MATERIALS AND

METHODS:

CCE extracts were obtained from commercially available cucumber. Active fractions were then purified by HPLC and analysed by high resolution mass spectrometry. The effect of CCE on intestinal chloride secretion was investigated in human colonic T84 cells, ex vivo mouse intestinal tissue using an Ussing chamber, and the two-electrode voltage-clamp technique to record calcium sensitive TMEM16A chloride currents in Xenopus laevis oocytes. In vivo, intestinal motility was investigated using the loperamide-induced C57BL/6 constipation mouse model. Ex vivo contractility of mouse colonic smooth muscles was assessed by isometric force measurements.

RESULTS:

CCE increased the short-circuit current (ΔIsc 34.47 ± µA/cm2) and apical membrane chloride conductance (ΔICl 95 ± 8.1 µA/cm2) in intestinal epithelial cells. The effect was dose-dependent, with an EC50 value of 0.06 µg/mL. CCE stimulated the endogenous TMEM16A-induced Cl- current in Xenopus laevis oocytes. Moreover, CCE increased the contractility of smooth muscle in mouse colonic tissue and enhanced small bowel transit in CCE treated mice compared to loperamide controls. Mass spectrometry suggested a cucurbitacin-like analogue with a mass of 512.07 g/mol underlying the bioactivity of CCE.

CONCLUSION:

A cucurbitacin-like analog present in CCE activates TMEM16A channels, which may have therapeutic potential in cystic fibrosis and intestinal hypodynamic disorders.
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Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Extraits de plantes / Chlorures / Cucumis sativus / Anoctamine-1 / Intestins / Canaux ioniques Limites: Animals / Humans / Male Langue: En Journal: Pharm Biol Année: 2021 Type de document: Article Pays d'affiliation: Inde

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Extraits de plantes / Chlorures / Cucumis sativus / Anoctamine-1 / Intestins / Canaux ioniques Limites: Animals / Humans / Male Langue: En Journal: Pharm Biol Année: 2021 Type de document: Article Pays d'affiliation: Inde
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