Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-03-22 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S499284

Minghui Xiu, Botong Li, Li He, Yan Shi, Yongxuan Zhang, Shihong Zhou, Yongqi Liu, Ningbo Wang, Jianzheng He

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引用次数: 0

Abstract

Background: Ulcerative colitis (UC) is a chronic intestinal inflammation that is prone to relapse and is difficult to fully recover; therefore, there is a need for safer alternative treatments. Caffeic acid (CA) is a natural polyphenolic compound that has antioxidant and anti-inflammatory properties. However, the beneficial effects and mechanisms of action of CA in UC remain unclear.

Purpose: This study evaluated the protective effect of CA against dextran sulfate sodium (DSS)-induced intestinal injury in Drosophila melanogaster model.

Results: Oral administration of CA significantly reduced body damage in UC flies, improved their survival rate, restored damaged digestion, and improved locomotion. CA supplementation significantly alleviated intestinal damage in UC flies by restoring excretion balance, repairing intestinal atrophy, improving acid-base balance imbalance, inhibiting intestinal structural destruction, inhibiting intestinal epithelial cell death and intestinal stem cell (ISC) excessive proliferation, and reducing the number of harmful bacteria. Mechanistic studies found that CA significantly reduced the expression of Toll and Imd pathway genes (including Myd88, Dif, PGRP-LC, Imd, Rel, and Dpt), reduced ROS levels and the expression of apoptosis-related genes (Debcl, Cyt-c-p, DrlCE, Dronc, and Dark), and increased ATP and MFN2 levels.

Conclusion: CA alleviated intestinal damage mainly by inhibiting the Toll and Imd signaling pathways and inhibiting apoptosis mediated by mitochondrial damage. These findings suggest that CA holds promise as a potential therapeutic for UC treatment.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.