Yujin Powder alleviates colonic oxidative injury in mice with dampness-heat diarrhea through the Keap1/Nrf2/GSH pathway: baicalein as a candidate key constituent.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Yujin Powder (YJP), a classic traditional Chinese medicinal formula for dampness-heat diarrhea (DHD), is widely used to treat damp-heat diarrhea in animals such as cattle and horses. However, the precise mechanisms by which YJP exerts its antioxidant effects in the treatment of DHD via the Keap1/Nrf2/GSH signaling pathway have not been fully elucidated. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which YJP ameliorates oxidative injury in the colonic epithelium of DHD mice and to identify candidate active constituents potentially involved in this process. MATERIALS AND METHODS: A DHD mouse model was established and treated with YJP. Therapeutic efficacy was assessed based on hematological parameters, serum biochemical indices, blood viscosity, colonic inflammatory responses, and histopathological changes. Transcriptomic analysis was performed to characterize gene expression alterations in the colon. Mechanistic validation was conducted using qRT-PCR, Western blotting, and multiplex immunofluorescence. Furthermore, an in vitro oxidative stress model using LPS-stimulated NCM-460 cells was established to verify the antioxidant activity of baicalein, a candidate key constituent of YJP identified through virtual screening and molecular dynamics simulations. RESULTS: YJP significantly alleviated diarrhea symptoms in DHD mice, improved body weight loss, corrected metabolic disorders, reduced systemic and colonic inflammatory responses, and restored colonic epithelial integrity. Mechanistic studies demonstrated that YJP enhanced antioxidant defense by regulating the Keap1/Nrf2/GSH pathway, thereby reducing oxidative stress and epithelial injury. Through virtual screening and molecular dynamics simulations, baicalein was identified as a candidate key constituent of YJP and showed the potential to form stable interactions with both Keap1 and Nrf2. In vitro experiments further confirmed that baicalein markedly attenuated LPS-induced oxidative stress in NCM-460 cells, supporting its role as an important contributor to the antioxidant effects of YJP. CONCLUSION: YJP alleviates colonic oxidative injury in DHD mice by regulating the Keap1/Nrf2/GSH pathway, while baicalein may represent a candidate key constituent contributing to this antioxidant effect.

Key Findings

• Yujin Powder (YJP) alleviates diarrhea symptoms and improves colonic epithelial integrity in mice with dampness-heat diarrhea (DHD).
• YJP enhances antioxidant defense by regulating the Keap1/Nrf2/GSH pathway, reducing oxidative stress and epithelial injury in the colon.
• Baicalein, identified via virtual screening and molecular dynamics simulations as a key constituent of YJP, forms stable interactions with Keap1 and Nrf2 and attenuates oxidative stress in vitro.

Clinical Significance

Citation

Han Mengling, Wang Baoshan, Jiang Lidonget al.. Yujin Powder alleviates colonic oxidative injury in mice with dampness-heat diarrhea through the Keap1/Nrf2/GSH pathway: baicalein as a candidate key constituent. Journal of ethnopharmacology. 2026-Oct-10.