Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila
Minghui Xiu,1,2,* Botong Li,3,* Li He,1 Yan Shi,3 Yongxuan Zhang,1 Shihong Zhou,1 Yongqi Liu,2,3 Ningbo Wang,4 Jianzheng He2,3,5 1College of Public Health, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China; 2Key Laboratory of Dunhuang Medi...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-03-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/caffeic-acid-protects-against-ulcerative-colitis-via-inhibiting-mitoch-peer-reviewed-fulltext-article-DDDT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849390255913828352 |
|---|---|
| author | Xiu M Li B He L Shi Y Zhang Y Zhou S Liu Y Wang N He J |
| author_facet | Xiu M Li B He L Shi Y Zhang Y Zhou S Liu Y Wang N He J |
| author_sort | Xiu M |
| collection | DOAJ |
| description | Minghui Xiu,1,2,* Botong Li,3,* Li He,1 Yan Shi,3 Yongxuan Zhang,1 Shihong Zhou,1 Yongqi Liu,2,3 Ningbo Wang,4 Jianzheng He2,3,5 1College of Public Health, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of Education, Lanzhou City, Gansu Province, People’s Republic of China; 3Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China; 4Tibetan Medical College, Qinghai University, Xining City, Qinghai Province, People’s Republic of China; 5Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzheng He, Email hejianzheng1006@163.comBackground: 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. Keywords: ulcerative colitis, caffeic acid, toll and Imd pathways, apoptosis, Drosophila melanogaster |
| format | Article |
| id | doaj-art-5b28efa0e8b341a69bcabe0f993cf1cf |
| institution | Kabale University |
| issn | 1177-8881 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj-art-5b28efa0e8b341a69bcabe0f993cf1cf2025-08-20T03:41:43ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-03-01Volume 1921572172101399Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in DrosophilaXiu MLi BHe LShi YZhang YZhou SLiu YWang NHe JMinghui Xiu,1,2,* Botong Li,3,* Li He,1 Yan Shi,3 Yongxuan Zhang,1 Shihong Zhou,1 Yongqi Liu,2,3 Ningbo Wang,4 Jianzheng He2,3,5 1College of Public Health, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of Education, Lanzhou City, Gansu Province, People’s Republic of China; 3Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China; 4Tibetan Medical College, Qinghai University, Xining City, Qinghai Province, People’s Republic of China; 5Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou City, Gansu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzheng He, Email hejianzheng1006@163.comBackground: 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. Keywords: ulcerative colitis, caffeic acid, toll and Imd pathways, apoptosis, Drosophila melanogasterhttps://www.dovepress.com/caffeic-acid-protects-against-ulcerative-colitis-via-inhibiting-mitoch-peer-reviewed-fulltext-article-DDDTulcerative colitiscaffeic acidtoll and imd pathwaysapoptosisdrosophila melanogaster |
| spellingShingle | Xiu M Li B He L Shi Y Zhang Y Zhou S Liu Y Wang N He J Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila Drug Design, Development and Therapy ulcerative colitis caffeic acid toll and imd pathways apoptosis drosophila melanogaster |
| title | Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila |
| title_full | Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila |
| title_fullStr | Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila |
| title_full_unstemmed | Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila |
| title_short | Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila |
| title_sort | caffeic acid protects against ulcerative colitis via inhibiting mitochondrial apoptosis and immune overactivation in drosophila |
| topic | ulcerative colitis caffeic acid toll and imd pathways apoptosis drosophila melanogaster |
| url | https://www.dovepress.com/caffeic-acid-protects-against-ulcerative-colitis-via-inhibiting-mitoch-peer-reviewed-fulltext-article-DDDT |
| work_keys_str_mv | AT xium caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT lib caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT hel caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT shiy caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT zhangy caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT zhous caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT liuy caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT wangn caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila AT hej caffeicacidprotectsagainstulcerativecolitisviainhibitingmitochondrialapoptosisandimmuneoveractivationindrosophila |