# Chlorogenic Acid Alleviates Chronic Stress-Induced Ileal Oxidative Stress and Apoptosis in Rats by Influencing Intestinal Flora and Activating Nrf2 Pathway

**Authors:** Wenjing Jiao, Haoyang Tan, Xin Cheng, Tianyuan Yang, Xuanpan Ding, Yaxin Ji, Haotian Yang, Jichen Sha, Guofeng Feng, Yuan Zhao, Honggang Fan

PMC · DOI: 10.3390/biology14111483 · 2025-10-24

## TL;DR

Chlorogenic acid helps protect the gut from stress damage by reducing oxidative stress and supporting healthy gut bacteria in rats.

## Contribution

This study reveals that chlorogenic acid mitigates stress-induced gut damage through Nrf2 pathway activation and modulation of gut microbiota.

## Key findings

- Chlorogenic acid reduced oxidative stress and apoptosis in the ileum of stressed rats.
- It activated the Nrf2 pathway by altering Keap1 conformation and increasing antioxidant proteins.
- Gut microbiota balance improved, with increased Lactobacillus abundance after CGA treatment.

## Abstract

Chronic stress can harm our digestive system by damaging the gut and affecting the bacteria that live in it. This study looked at whether chlorogenic acid, a natural compound found in foods like coffee and fruits, can protect the gut from stress-related damage. Using a rat model, we found that chlorogenic acid reduced harmful oxidative stress, prevented cell death in the gut lining, and helped maintain healthy gut bacteria. It also activated a natural antioxidant pathway in the body. These results suggest that chlorogenic acid could be used as a dietary supplement to help protect intestinal health under stress. This research offers a natural approach to supporting gut health and overall well-being.

Background: Chronic stress is implicated in the pathogenesis of gastrointestinal disorders, with reactive oxygen species (ROS) contributing significantly. Chlorogenic acid (CGA), a polyphenolic compound, exhibits antioxidant properties. This study investigated whether CGA mitigates ROS-mediated oxidative stress and apoptosis in chronic stress-induced ileal injury. Methods: Rats were subjected to restraint stress for 21 days, with/without CGA (100 mg/kg, gavage). CGA’s mechanism was elucidated by assessing ileal flora, oxidative stress markers, apoptosis, structural changes, and the Nrf2 pathway. Results: CGA restored ileal structure, attenuated ROS and MDA levels, elevated GSH and SOD levels, and reduced apoptosis-associated proteins. CGA stabilized conformation bound to Keap1, deregulating Keap1’s negative regulation of Nrf2, thereby increasing Nrf2 and downstream protein expression (HO-1 and NQO1). Gut microbiota imbalance was corrected, with increased Lactobacillus abundance post-CGA intervention. Conclusions: CGA alleviates chronic stress-induced ileal oxidative stress and apoptosis, which relates closely to Nrf2 pathway activation and modulation of intestinal microflora.

## Linked entities

- **Proteins:** GABPA (GA binding protein transcription factor subunit alpha), KEAP1 (kelch like ECH associated protein 1), HMOX1 (heme oxygenase 1), NQO1 (NAD(P)H quinone dehydrogenase 1)
- **Chemicals:** chlorogenic acid (PubChem CID 1794427), GSH (PubChem CID 124886), MDA (PubChem CID 1614)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Keap1 (Kelch-like ECH-associated protein 1) [NCBI Gene 117519] {aka Inrf2}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Nqo1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 24314] {aka Dia4}
- **Diseases:** gastrointestinal disorders (MESH:D005767), ileal injury (MESH:D007077)
- **Chemicals:** ROS (MESH:D017382), GSH (MESH:D005978), polyphenolic compound (-), CGA (MESH:D002726), MDA (MESH:D015104)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Lactobacillus (genus) [taxon 1578]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12650661/full.md

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Source: https://tomesphere.com/paper/PMC12650661