Endometriosis (EMs) is a common gynecological disorder characterized by abnormal growth of the endometrial stroma and glands outside the uterus. Tanshinone IIA, the active component of Chinese medicine Danshen (
Salvia miltiorrhiza
Bge.), has a number of pharmacological effects such as anti-inflammation and anti-oxidation and serves a significant role in the treatment of EMs. In the present study, network pharmacology and experimental validation were used to elucidate the potential mechanism of tanshinone IIA for treating EMs. Several databases were used to collect information on EMs and tanshinone IIA and cross-targets for tanshinone IIA and EMs finally obtained. A total of 64 common targets were found between tanshinone IIA and EMs. Subsequently, a protein-protein interaction network was constructed, a total of 14 core targets were screened for enrichment analysis. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The network pharmacology showed that intercellular adhesion molecule (ICAM)-1, MMP-9 and VEGF are the core targets while PI3K/AKT pathway and mTOR pathway are the main signaling pathways through which tanshinone IIA regulates relevant biological processes to intervene in EMs. Finally, the therapeutic role and mechanism of tanshinone IIA on EMs was verified
in vivo
. Female Sprague-Dawley rats were treated by autologous transplantation to establish EMs.
Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ICAM-1, MMP-9 and VEGF in ectopic endometrial tissues of rats was determined by immunohistochemical. The expression of PI3K/Akt/mTOR pathway-related proteins and genes was detected by western blotting and quantitative PCR. It was found that tanshinone IIA treatment significantly decreased the formation of ectopic endometrium by reducing serum levels of TNF-α and IL-1β, and down regulating the levels of ICAM-1, MMP-9 and VEGF in ectopic uterine tissue. In addition, tanshinone IIA can also block the activation of PI3K/Akt/mTOR signaling pathway by reducing the expression of related proteins and genes. In conclusion, tanshinone IIA can regulate adhesion, invasion and angiogenesis, thereby improving the pathological morphology of ectopic endometrium and inhibiting the formation of ectopic lesions. The PI3K/Akt/mTOR signaling pathway may play a key role in controlling this process.