Qingshu Yiqi decoction ameliorates exertional heat stroke-induced intestinal barrier injury via NF-κB/MLC pathway and gut microbiota

Weiyi Ma; Man Wang; Jikuai Chen; Yawei Wang; Juelin Chen; Yankun Pei; Yitong Gong; Jianyao You; Yangyang Cao; Jiawei Zhou; Jun Ma; Wenjun Chang; Hanyu Zhu; Qing Song; Lei Li; Shuogui Xu; Haiyan Zhu

doi:10.1016/j.phymed.2025.156723

Qingshu Yiqi decoction ameliorates exertional heat stroke-induced intestinal barrier injury via NF-κB/MLC pathway and gut microbiota

Phytomedicine. 2025 Jul 25:143:156723. doi: 10.1016/j.phymed.2025.156723. Epub 2025 May 2.

Authors

Weiyi Ma¹, Man Wang², Jikuai Chen³, Yawei Wang⁴, Juelin Chen⁴, Yankun Pei⁴, Yitong Gong⁴, Jianyao You⁴, Yangyang Cao⁴, Jiawei Zhou⁴, Jun Ma⁵, Wenjun Chang⁶, Hanyu Zhu⁷, Qing Song⁵, Lei Li⁸, Shuogui Xu⁹, Haiyan Zhu¹⁰

Affiliations

¹ Department of Emergency, First Medical Center of Chinese PLA General Hospital, Fuxing Road No 28, Haidian, Beijing, Postal code, 100853, China; Heatstroke Treatment and Research Center of PLA, Sanya, China.
² Department of Rehabilitation and Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Changhai Road No 168, Yangpu, Shanghai, Postal code, 200433, China.
³ Department of Health Toxicology, Faculty of Naval Medicine, Naval Medical University, Changhai Road No 168, Yangpu, Shanghai, Postal code, 200433, China.
⁴ Department of Emergency, Changhai Hospital, Naval Medical University, Changhai Road No 168, Yangpu, Shanghai, Postal code, 200433, China.
⁵ Department of Critical Care Medicine, Hainan Hospital, Chinese PLA General Hospital, Sanya, China; Heatstroke Treatment and Research Center of PLA, Sanya, China.
⁶ Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
⁷ Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China.
⁸ Department of Emergency, Changhai Hospital, Naval Medical University, Changhai Road No 168, Yangpu, Shanghai, Postal code, 200433, China; Heatstroke Treatment and Research Center of PLA, Sanya, China; Department of Emergency, the Second Naval Hospital of Southern Theater Command of PLA, Sanya, China. Electronic address: relayinch@smmu.edu.cn.
⁹ Department of Emergency, Changhai Hospital, Naval Medical University, Changhai Road No 168, Yangpu, Shanghai, Postal code, 200433, China. Electronic address: shuogui_xu@smmu.edu.cn.
¹⁰ Department of Emergency, First Medical Center of Chinese PLA General Hospital, Fuxing Road No 28, Haidian, Beijing, Postal code, 100853, China; Heatstroke Treatment and Research Center of PLA, Sanya, China. Electronic address: xiaoyanzibj301@163.com.

PMID: 40339554
DOI: 10.1016/j.phymed.2025.156723

Abstract

Background: Exertional heat stroke (EHS) is a life-threatening condition induced by high-temperature environments, which poses significant health risks. The Qingshu Yiqi Decoction (QSYQD) is a traditional Chinese medicine (TCM) formula that is known to clear summer heat, replenish Qi, and protect intestinal function. However, experimental evidence and mechanistic insights into its role in EHS prevention are limited.

Purpose: The aim of this study is to evaluate the protective effects of QSYQD against EHS-induced hyperthermia and multi-organ injury and investigate the underlying molecular mechanisms.

Methods: An EHS rat model was established using treadmill exercise in a high-temperature environment. The rats were pretreated with low, medium, or high doses of the QSYQD. The intestinal barrier function was assessed using biomarkers, an ultrastructural analysis, and key protein expressions. Network pharmacology was used to identify potential targets, and molecular mechanisms were validated using western blot. The gut microbiota composition was analyzed using 16S rRNA sequencing.

Results: The QSYQD significantly alleviated hyperthermia and multi-organ injury in the EHS rats, and the medium dose had the most pronounced effects. It preserved intestinal barrier integrity by maintaining the tight junction protein levels and reducing biomarkers of epithelial damage. Network pharmacology and experimental validation revealed that the QSYQD inhibited the NF-κB and MLC signaling pathways, key regulators of intestinal barrier function. Additionally, the QSYQD altered the gut microbiota composition and notably increased the abundance of Lactobacillus, that has known heat stress protective effects.

Conclusions: QSYQD protects against EHS-induced damage by preserving intestinal barrier integrity, modulating gut microbiota, and inhibiting the NF-κB and MLC signaling pathways. Future studies will focus on identifying active compounds within QSYQD that enhance heat tolerance and provide EHS protection.

Keywords: Exertional heat stroke; Gut microbiota; Heat stress; Intestinal barrier; Network pharmacology.

MeSH terms

Animals
Disease Models, Animal
Drugs, Chinese Herbal* / pharmacology
Gastrointestinal Microbiome* / drug effects
Heat Stroke* / drug therapy
Intestinal Mucosa / drug effects
Intestinal Mucosa / metabolism
Intestines / drug effects
Male
NF-kappa B* / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects

Substances

NF-kappa B
Drugs, Chinese Herbal