Regulation of inflammation by Chaihu-Shugan-San: Targeting the IL-17/ NF-κB pathway to combat breast cancer-related depression

Qu Z, Li H, Qiang F, Liu K, Wu S, Li J, Zou X · Phytomedicine · 2025 July

DOI 10.1016/j.phymed.2025.156836

Objective

To investigate the effects of Chaihu-Shugan-San (CSS) on breast cancer-related depression (BCRD) in a mouse model and to elucidate its mechanisms, particularly its impact on microglial polarization through the IL-17/ NF-κB pathway.

Conclusions

CSS treatment significantly improved depression-like behaviors and retarded tumor growth in mice, with outcomes indicating that CSS inhibits the IL-17/ NF-κB pathway, facilitates the transformation of microglia from M1 to M2 phenotype, and reduces neuroinflammation by targeting IL-17.

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Insights

Chaihu-Shugan-San, a traditional Chinese medicine, improves breast cancer-related depression by regulating the IL-17/NF-κB pathway and modulating microglial polarization.

The methodology of this study involved the construction and treatment of a mouse model exhibiting breast cancer-related depression with Chaihu-Shugan-San. This was followed by behavioral testing, histochemical staining, and small animal imaging to measure depressive behaviors and tumor development. The research also involved RNA sequencing analysis and several other validation methods, including Western blot and quantitative qRT-PCR, to inspect the treatment's effects. In addition, in vitro tests were executed on the stimulated microglia with various interventions to verify the regulatory role of the IL-17 protein on the treatment. The results showed that Chaihu-Shugan-San treatment improved depression-like behaviors and inhibited tumor growth in mice. This improvement was closely linked to its regulation of the IL-17/ NF-κB pathway. Chaihu-Shugan-San inhibited this pathway and promoted a transformation from a pro-inflammatory microglial phenotype to an anti-inflammatory one, thereby, reducing neuroinflammation. The treatment's modulatory effect was similar to the effects of IL-17 antagonists, suggesting that Chaihu-Shugan-San might relieve symptoms by targeting IL-17. Three bioactive compounds, Saikosaponin A, Saikosaponin C, and Saikosaponin D, were identified in Chaihu-Shugan-San, which likely play a crucial role in its therapeutic effect.