Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling DOI Creative Commons
Jing Li, Zhijun Geng, L.X. Yin

и другие.

Antioxidants, Год журнала: 2025, Номер 14(5), С. 524 - 524

Опубликована: Апрель 27, 2025

Inflammatory bowel disease (IBD), encompassing Crohn's and ulcerative colitis, is characterized by chronic intestinal inflammation epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired homeostasis in cells (IECs) disrupts redox balance, exacerbates oxidative stress, triggers apoptosis, further compromising integrity. This study investigated the therapeutic effects of Engeletin (Eng), dihydroflavonoid from Smilax glabra Roxb., dextran sulfate sodium (DSS)-induced colitis mice colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated symptoms, including weight loss, activity index (DAI) scores, colon shortening, while restoring integrity through upregulation tight junction proteins (ZO-1, claudin-1) goblet cell preservation. suppressed NF-κB-mediated activated Nrf2 antioxidant pathway, well reduced stress markers (MDA, CAT, GSH, SOD). It attenuated apoptosis balancing pro- anti-apoptotic (Bax/Bcl2, c-caspase3) ameliorated via enhanced ATP production, mtDNA levels, complex I/IV activity. Mechanistically, AMPK/SIRT1/PGC-1α axis, pharmacological inhibition PGC-1α abolished its protective effects. These findings demonstrate that alleviates targeting signaling, offering multitargeted strategy for therapy.

Язык: Английский

Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling DOI Creative Commons
Jing Li, Zhijun Geng, L.X. Yin

и другие.

Antioxidants, Год журнала: 2025, Номер 14(5), С. 524 - 524

Опубликована: Апрель 27, 2025

Inflammatory bowel disease (IBD), encompassing Crohn's and ulcerative colitis, is characterized by chronic intestinal inflammation epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired homeostasis in cells (IECs) disrupts redox balance, exacerbates oxidative stress, triggers apoptosis, further compromising integrity. This study investigated the therapeutic effects of Engeletin (Eng), dihydroflavonoid from Smilax glabra Roxb., dextran sulfate sodium (DSS)-induced colitis mice colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated symptoms, including weight loss, activity index (DAI) scores, colon shortening, while restoring integrity through upregulation tight junction proteins (ZO-1, claudin-1) goblet cell preservation. suppressed NF-κB-mediated activated Nrf2 antioxidant pathway, well reduced stress markers (MDA, CAT, GSH, SOD). It attenuated apoptosis balancing pro- anti-apoptotic (Bax/Bcl2, c-caspase3) ameliorated via enhanced ATP production, mtDNA levels, complex I/IV activity. Mechanistically, AMPK/SIRT1/PGC-1α axis, pharmacological inhibition PGC-1α abolished its protective effects. These findings demonstrate that alleviates targeting signaling, offering multitargeted strategy for therapy.

Язык: Английский

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