Curcumin treats endometriosis in mice by the HIF signaling pathway

Objective: The aim of this study was to investigate whether curcumin has a therapeutic effect on endometriosis (EM) and to determine the specific mechanism. Methods: Network pharmacology was used to obtain the core targets of curcumin for the treatment of EM and the specific biologic processes involved. A mouse model of EM was constructed and divided into different groups, as follows: control, negative control, curcumin, and denogestrel. The number, volume, and degree of adhesions of the lesions in each group were measured. The levels of IL-1 beta, IL-6, and VEGFA in the peritoneal cavity were measured by enzyme-linked immunosorbent assay (ELISA). Western blot and Q-PCR were used to detect HIF-la and VEGFA proteins and gene expression levels in the lesion tissues. Results: Network pharmacology suggested that curcumin treated EM through the HIF signaling pathway, of which IL-6, HIF-1 alpha, and VEGFA are key targets. The number of lesions, volume, and degree of adhesions were significantly reduced in the curcumin group compared to the negative control group and the control group (P < 0.05). IL-6, IL-1 beta, and VEGFA levels were reduced in the peritoneal fluid (P < 0.05). HIF-1 alpha and VEGFA protein and gene levels were significantly reduced in the lesions (P < 0.05). No modulation of HIF-1 alpha was shown by denogestins. Conclusion: Curcumin played a role in the treatment of EM by modulating the HIF signaling pathway, improving the local hypoxia of the lesion, and reducing the inflammatory state of EM.