Lichong decoction improves inflammatory microenvironment and alleviates fibrosis in uterine leiomyoma via targeting CXCL8

Lichong decoction (LD) is extensively employed in the treatment of uterine leiomyoma (ULM), demonstrating remarkable clinical effectiveness with an absence of notable adverse reactions. Its composition aligns with the traditional Chinese medicine (TCM) etiology of ULM, making it a highly suitable therapy. Nonetheless, the precise mechanisms underlying its therapeutic actions remain to be fully elucidated.

The objective of this study was to clarify the therapeutic mechanism of LD improving ULM.

The effects of LD on ULM cell viability, proliferation, and apoptosis were assessed using CCK-8, crystal violet staining, EdU incorporation, TUNEL, and Annexin V-FITC/PI assays. Gene microarray was used to profile differential gene expression after LD treatment. A rat ULM model was created to evaluate LD's anti-tumor efficacy, measuring body weight, uterine weight index, and sex hormone levels. Histopathological changes were analyzed with hematoxylin and eosin staining, Masson's trichrome staining, and transmission electron microscopy. Protein and RNA expression changes were analyzed via immunohistochemistry, western blotting, and qPCR. UHPLC-QE-MS enabled a detailed non-targeted LD analysis. Key components were identified through their correlation with serum sex hormones and inflammatory cytokines, and then examined by molecular docking studies.

Experiments showed that LD reduced ULM cell viability and induced apoptosis. Gene expression profiling identified 313 differentially expressed genes. Enrichment analysis combined with experimental validation demonstrated that LD can reduce ULM fibrosis and inflammation by inhibiting the CXCL8/PI3K/AKT pathway. The analysis identified 494 primary compounds and 87 serum components in LD. Key compounds such as formononetin, palmatine, curcumenol, and hecogenin, which exhibit high affinity for CXCL8, may contribute to the anti-inflammatory and anti-tumor properties of LD.

This study demonstrates that LD effectively inhibits ULM proliferation and fibrosis by improving the inflammatory microenvironment, primarily through the inhibition of CXCL8. These findings highlight the therapeutic potential of LD for ULM and provide new insights into its mechanisms.