Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea
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 chlori...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00270/full |
| _version_ | 1811289043434995712 |
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| author | Yu Jiang Bo Yu Hong Yang Tonghui Ma |
| author_facet | Yu Jiang Bo Yu Hong Yang Tonghui Ma |
| author_sort | Yu Jiang |
| collection | DOAJ |
| description | 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 Ca2+ concentration as well as the other major enterocyte chloride channel CFTR. 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 CaCCs, the inhibitory effect was partially through inhbition of basolateral K+ channel acitivty, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea. |
| first_indexed | 2024-04-13T03:46:52Z |
| format | Article |
| id | doaj.art-645712fb604b41cfbec56654b2301e97 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T03:46:52Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-645712fb604b41cfbec56654b2301e972022-12-22T03:03:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-08-01710.3389/fphar.2016.00270211157Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrheaYu Jiang0Bo Yu1Hong Yang2Tonghui Ma3Liaoning normal universityLiaoning normal universityLiaoning normal universityDalian Medical UniversitySecretory 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 Ca2+ concentration as well as the other major enterocyte chloride channel CFTR. 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 CaCCs, the inhibitory effect was partially through inhbition of basolateral K+ channel acitivty, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00270/fullCaCCinhibitorshort-circuit currentTMEM16AShikoninRotaviral diarrhea |
| spellingShingle | Yu Jiang Bo Yu Hong Yang Tonghui Ma Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea Frontiers in Pharmacology CaCC inhibitor short-circuit current TMEM16A Shikonin Rotaviral diarrhea |
| title | Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea |
| title_full | Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea |
| title_fullStr | Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea |
| title_full_unstemmed | Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea |
| title_short | Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea |
| title_sort | shikonin inhibits intestinal calcium activated chloride channels and prevents rotaviral diarrhea |
| topic | CaCC inhibitor short-circuit current TMEM16A Shikonin Rotaviral diarrhea |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00270/full |
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