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• MGL significantly ameliorated CD-like colitis. • MGL protected the intestinal barrier through inhibiting IEC apoptosis. • The effect of MGL might be partly mediated via suppressing PI3K/AKT signalling pathway in IECs. Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved. Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis. The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro. MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The present study was designed to investigate the inhibitory effects of fluorofenidone on Ang II-induced apoptosis in renal tubular cells and the related signaling pathway. Methods: Rat proximal tubular epithelial cells (NRK-52E) were used to examine the anti-apoptosis effects of fluorofenidone. Cell proliferation was assessed by methyl thiazolyl tetrazolium assay. Apoptosis was examined by AO/EB staining and TUNEL assay. The expression of Fas/FasL pathway members, including Fas, FasL, Bax, Bcl-2, Caspase-8, and Caspase-3 was detected by real-time RT-PCR and/or Western blot, respectively. The activity of Caspase-8 and Caspase-3 was detected by spectrophotometry. Results: Fluorofenidone didn''t affect the proliferation of NRK-52E cells, but significantly inhibited the apoptosis of NRK-52E cells induced by Ang II. Fluorofenidone significantly reduced Ang II-induced increases in Fas, FasL, Bax, Caspase-8 and Caspase-3 at the mRNA level. Consistent with these observations, fluorofenidone also prevented Ang II-mediated up-regulation of FasL and Bax at the protein level. Additionally, Ang II-induced activation of Caspase-8 and Caspase-3 as well as Ang II-initiated downregulation of Bcl-2 at both mRNA and protein levels was all prevented by fluorofenidone. Conclusions: Fluorofenidone can inhibit Ang II-induced apoptosis of renal tubular cells through blockage of the Fas/FasL pathway. [Copyright &y& Elsevier]