Abstract
Background and Purpose: Adenomyosis causes pain, abnormal bleeding, and
infertility. Epithelial-mesenchymal transition (EMT) plays a critical
role in the pathogenesis of adenomyosis. Current therapies are mainly
hormone-dependent and their termination led to aggravations. To develop
novel pharmacological treatment is necessary. Safflower was widely used
to treat gynecological disease in China, the effect of hydroxysafflower
yellow A (HSYA) that is the major active component of Safflower on
adenomyosis remains unclear. We investigated whether HSYA ameliorates
adenomyosis, and further revealed its potential target and mechanisms.
Experimental Approach: Adenomyosis was induced in female ICR mice by
oral administration of tamoxifen on days 2-5 after birth. At the 16th
week, HSYA were administrated for 3 weeks. Adenomyosis development,
autophagy activity, and involved mechanisms were analyzed using HE and
Masson staining, western blotting, immunofluorescence, and
RNA-sequencing. Furthermore, network pharmacology and molecular docking
were applied to assess the potential target of HSYA. Key Results: HSYA
ameliorates adenomyosis via promoting autophagy and ameliorating the
activation of PI3K-AKT-mTOR. Isocitrate dehydrogenase1(IDH1) was found
to be the potential target of HSYA. After IDH1 was knocked down by
si-RNA, autophagy was activated, and EMT was attenuated via inhibiting
PI3K-AKT-mTOR by HSYA. Conclusions and Implications: HSYA significantly
ameliorates adenomyosis, and IDH1-autophagy-EMT plays an important role
in the progress of adenomyosis. It will shed new light on a potential
novel therapeutic strategy for adenomyosis.