The natural statin α,β-dehydromonacolin K exerts anti-secretory effect in human intestinal epithelial cells via a nonsense-mediated mRNA decay-dependent mechanism.

ABSTRACT: cAMP-induced intestinal chloride secretion plays a pivotal role in the pathogenesis of secretory diarrheas. In this study, we investigated the antisecretory effects of α,β-dehydromonacolin K, a derivative of lovastatin from Aspergillus sclerotiorum, on cAMP-induced chloride secretion in human T84 cells and fluid secretion in human colonoids. Short-circuit current analyses and swelling assays were used to investigate the effects of α,β-dehydromonacolin K on chloride transport and fluid secretion, respectively. Proteomic analyses were performed to determine the potential anti-diarrheal mechanisms of α,β-dehydromonacolin K. In T84 cells, α,β-dehydromonacolin K inhibited cAMP-induced chloride secretion with an IC50 of ∼ 6.32 μM. Apical chloride current analyses demonstrated that α,β-dehydromon

SUBMITTER: Satitsri S 

PROVIDER: S-EPMC12377102 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature