ArticleFrontiers in pharmacology2016
Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- Shikonin inhibits multiple tumor malignant phenotypes and is associated with Hedgehog pathway downregulation in lung adenocarcinoma.Scientific reports · 2025Article
- Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation.Redox biology · 2024Article
- In Vitro Anti-Rotaviral Activity of Bavachin Isolated fromVeterinary sciences · 2024Article
- Treading a HOSTile path: Mapping the dynamic landscape of host cell-rotavirus interactions to explore novel host-directed curative dimensions.Virulence · 2021Review
- The diverse roles of TMEM16A CaJournal of advanced research · 2021Review
- Emerging Modulators of TMEM16A and Their Therapeutic Potential.The Journal of membrane biology · 2021Review
- The CaActa pharmaceutica Sinica. B · 2021Review
- HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.PLoS biology · 2021Article
- Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.Journal of experimental pharmacology · 2021Review
- Modulation of Calcium-Activated Chloride Currents in Rat Neurons with New 2-Aminotiophene-3-Carboxylic Acid Derivatives.Doklady. Biochemistry and biophysics · 2020Article
- Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives.Viruses · 2020Review
- TMEM16A CaJournal of advanced research · 2020Article
- Agonism of the TMEM16A calcium-activated chloride channel modulates airway smooth muscle tone.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- TMEM16A in Cystic Fibrosis: Activating or Inhibiting?Frontiers in pharmacology · 2019Review
- Plumbagin Prevents Secretory Diarrhea by Inhibiting CaCC and CFTR Channel Activities.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl(-) current in a dose-dependent manner, with IC50 value of 1.5 μM. Short-circuit current measurement showed that shikonin exhibited inhibitory effect against CCh-induced Cl(-) currents in mouse colonic epithelia but did not affect cytoplasmic Ca(2+) concentration as well as the other major enterocyte chloride channel conductance regulator. Characterization study found that shikonin inhibited basolateral K(+) channel activity without affecting Na(+)/K(+)-ATPase activities. In vivo studies revealed that shikonin significantly delayed intestinal motility in mice and reduced stool water content in a neonatal mice model of rotaviral diarrhea without affecting the viral infection process in vivo. Taken together, the results suggested that shikonin inhibited enterocyte calcium-activated chloride channels, the inhibitory effect was partially through inhbition of basolateral K(+) channel activity, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea.
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