Artemisinins Show Promise in Treating PCOS Through LONP1-CYP11A1 Interaction: Study

Early results in human and animal models suggest that artemisinins might target all aspects of PCOS by suppressing ovarian androgen synthesis, researchers reported.

The study revealed that artemisinins reduced blood testosterone levels and cystic ovarian follicles in PCOS-like mice and improved litter size and embryo implantation in PCOS-like rats. Similarly, artemisinin treatment decreased levels of 2 blood markers of PCOS and reduced ovarian cysts in 19 human participants with the condition. The majority of participants (63%) also regained normal menstrual cycles.

PCOS, a common endocrine disorder affecting women of reproductive age, is characterized by irregular menstrual cycles, excess androgen production, and ovarian cysts. Current treatments primarily focus on managing symptoms such as infertility, insulin resistance, and hormonal imbalance. However, the underlying mechanisms driving PCOS have remained elusive until now. Current treatment options like birth control pills and metformin tend to target only specific symptoms of the condition.

Despite the high prevalence of PCOS, specific pharmacologic intervention for PCOS is challenging. In the study, Yang Liu, Fudan University, Shanghai, China, and colleagues identified artemisinins as anti-PCOS agents.

The finding demonstrated artemisinin derivatives' efficacy in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia by suppressing ovarian androgen synthesis.

The following were the key findings of the study:

• Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction.
• Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation.
• Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins.

Artemisinins directly bind to LONP1, initiating the interaction between LONP1 and CYP11A1, promoting CYP11A1 degradation, subsequently inhibiting ovarian androgen synthesis, and curbing PCOS. Contrarily, the androgenic inducer disrupts LONP1-CYP11A1 interaction and aggravates PCOS.

"Overall, our research underscores the promising potential of artemisinins as effective medications for the holistic management of PCOS.," the researchers wrote.

"This discovery reveals a newly identified interaction between LONP1 and CYP11A1, which artemisinins amplify to regulate androgen synthesis, suggesting new approaches for intervening in PCOS by targeting the LONP1-CYP11A1 interaction," they concluded.

Reference:

Liu Y, Jiang JJ, Du SY, Mu LS, Fan JJ, Hu JC, Ye Y, Ding M, Zhou WY, Yu QH, Xia YF, Xu HY, Shi YJ, Qian SW, Tang Y, Li W, Dang YJ, Dong X, Li XY, Xu CJ, Tang QQ. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction. Science. 2024 Jun 14;384(6701):eadk5382. doi: 10.1126/science.adk5382. Epub 2024 Jun 14. PMID: 38870290.