Background Oxidative stress has been firmly established as a pivotal contributor to the pathogenesis of inflammatory bowel disease, diabetes mellitus, Alzheimer’s disease, and other multifactorial disorders. Our previous findings have demonstrated the extracts from Sonchus brachyotus DC. (SBE) mitigates intestinal oxidative stress through interactions between the oxidative stress biomarkers and gut microbiota. However, we did not focus on the mechanism by which SBE exerts antioxidant stress effects through regulating metabolites and genes, nor the correlation between the two and gut microbiota. Therefore, this study aimed to elucidate the underlying mechanism by which SBE mitigates oxidative stress through the gut microbiota, metabolites, and genes. Results Supplementation with SBE exerts a promising regulatory effect on oxidative stress by modulating key oxidative stress biomarkers (e.g., GSH, SOD, etc.) in serum, intestine, liver, and brain tissues in ethanol-model mice. And the SBE treatment exhibited a notable reparative effect on intestine, liver, and brain tissue damage. Concomitantly, 16S rRNA and ITS sequencing revealed significant alterations in the composition of intestinal bacteria and fungi in SBE-treated mice, suggesting the restoration of gut microbiota homeostasis. Spearman correlation analysis further indicated significant associations (p < 0.05) between gut microbes, particularly fungal genera, and oxidative stress biomarkers. Notably, the abundance of specific fungal genera (Alternaria and Pichia), the levels of 14,15-DiHETrE, 5-Hydroxyindole-3-acetic acid, and prostaglandin C2 key metabolites of the serotonergic synapse pathway, and the expression of Fas and Tnfsf10 key genes of apoptosis signaling pathway were significantly correlated (p < 0.05) based on the constructed correlation network. This mechanism likely triggers coordinated changes in metabolites and gene expression associated with the serotonergic synapse and apoptosis signaling pathways, ultimately leading to multi-targeted amelioration of oxidative stress. Molecular docking further revealed that trigonelline, mesaconic acid, and salicylic acid, bioactive components of SBE, may exhibit considerable binding affinity with Fas and Tnfsf10, providing a potential structural basis for SBE’s regulatory effects on oxidative stress via modulation of the apoptotic signaling. Conclusions The antioxidant effects of SBE likely involve multi-pathway and multi-target mechanisms, consistent with the combinatorial properties of its herbs constituents. These findings lays a foundation for subsequent research. <MediaObject ID="MOESM2"> <VideoObject FileRef="MediaObjects/40168_2025_2221_MOESM2_ESM.mp4" VideoID="5P4JY7oP5stEf1BAKPknNB"> <Caption Language="En" xml:lang="en"> <CaptionContent> Video Abstract </CaptionContent> </Caption> </VideoObject> </MediaObject> Graphical Abstract

Regulation on microbial composition,serotonergic synapse, and apoptotic signaling pathway by extracts fromSonchus brachyotus DC. (SBE) to improve ethanol-induced acute oxidative stress in mice

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2025年10月29日

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Yang Juan,
Tian Wei,
Zhou Weiwei,
Shi dongdong,
Zhang Mengjie,
Wang Xuefeng,
Li Xianglong,
Sun Yuelong,
Zhao Jinhua,
Li Xiumei

摘要

Background

Oxidative stress has been firmly established as a pivotal contributor to the pathogenesis of inflammatory bowel disease, diabetes mellitus, Alzheimer’s disease, and other multifactorial disorders. Our previous findings have demonstrated the extracts from Sonchus brachyotus DC. (SBE) mitigates intestinal oxidative stress through interactions between the oxidative stress biomarkers and gut microbiota. However, we did not focus on the mechanism by which SBE exerts antioxidant stress effects through regulating metabolites and genes, nor the correlation between the two and gut microbiota. Therefore, this study aimed to elucidate the underlying mechanism by which SBE mitigates oxidative stress through the gut microbiota, metabolites, and genes.

Results

Supplementation with SBE exerts a promising regulatory effect on oxidative stress by modulating key oxidative stress biomarkers (e.g., GSH, SOD, etc.) in serum, intestine, liver, and brain tissues in ethanol-model mice. And the SBE treatment exhibited a notable reparative effect on intestine, liver, and brain tissue damage. Concomitantly, 16S rRNA and ITS sequencing revealed significant alterations in the composition of intestinal bacteria and fungi in SBE-treated mice, suggesting the restoration of gut microbiota homeostasis. Spearman correlation analysis further indicated significant associations (p < 0.05) between gut microbes, particularly fungal genera, and oxidative stress biomarkers. Notably, the abundance of specific fungal genera (Alternaria and Pichia), the levels of 14,15-DiHETrE, 5-Hydroxyindole-3-acetic acid, and prostaglandin C2 key metabolites of the serotonergic synapse pathway, and the expression of Fas and Tnfsf10 key genes of apoptosis signaling pathway were significantly correlated (p < 0.05) based on the constructed correlation network. This mechanism likely triggers coordinated changes in metabolites and gene expression associated with the serotonergic synapse and apoptosis signaling pathways, ultimately leading to multi-targeted amelioration of oxidative stress. Molecular docking further revealed that trigonelline, mesaconic acid, and salicylic acid, bioactive components of SBE, may exhibit considerable binding affinity with Fas and Tnfsf10, providing a potential structural basis for SBE’s regulatory effects on oxidative stress via modulation of the apoptotic signaling.

Conclusions

The antioxidant effects of SBE likely involve multi-pathway and multi-target mechanisms, consistent with the combinatorial properties of its herbs constituents. These findings lays a foundation for subsequent research.

Video Abstract

Graphical Abstract