Donepezil attenuates inflammation and apoptosis in ulcerative colitis via regulating LRP1/AMPK/NF-κB signaling.

This article focuses on the specific effects and mechanisms of donepezil (DNPZ) hydrochloride on inflammation and apoptosis in ulcerative colitis (UC). In vivo and in vitro models of UC were established using dextran sodium sulfate (DSS)-induced mice and NCM460 cells, respectively. Following oral administration of DNPZ, body weight, disease activity index (DAI) scores and colon lengths of mice were recorded. Histopathological damage was detected employing hematoxylin and eosin (H&E) staining. Inflammatory factors were tested using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Apoptosis was estimated utilizing terminal deoxynucleotidyl transferase dUTP nick-end labeling and western blot. Low-density lipoprotein receptor-related protein 1 (LRP1)/AMP activated protein kinase (AMPK)/nuclear factor-κB (NF- κB) signaling proteins were detected utilizing western blot. NCM460 cell viability was assessed by cell counting kit (CCK)-8. We found that DNPZ partially restored body weight, reduced DAI scores and attenuated intestinal pathological damage in DSS-induced mice. Additionally, inflammatory factors decreased significantly after DNPZ treatment, accompanied by reduced apoptosis level. Phosphorylation (p)-AMPK increased and p-p65 decreased after DNPZ treatment, whereas LRP1 knockdown showed the opposite effect. Moreover, DNPZ treatment greatly restored NCM460 cell viability after DSS stimulation. DNPZ attenuated DSS-induced inflammation and apoptosis in NCM460 cells, which was reversed by LRP1 knockdown. In summary, DNPZ hydrochloride attenuates inflammation and apoptosis in UC via LRP1/AMPK/NF-κB signaling.