Trilobatin alleviates polycystic ovary syndrome in rats by targeting SIRT2-Mediated PKM2 acetylation in glycolysis and mitochondrial function
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that severely impacts female fertility. The natural dihydrochalcone trilobatin (TLB) has shown potential in managing metabolic diseases; however, its therapeutic effect on PCOS and the underlying mechanisms remain unexplored.
PURPOSE: To investigate the therapeutic potential of TLB for PCOS and to elucidate the mechanistic basis, focusing on glycolytic metabolism and mitochondrial function in granulosa cells (GCs).
METHODS: A dehydroepiandrosterone (DHEA) -induced PCOS rat model was established and treated with two different doses of TLB or metformin.Therapeutic effects were assessed based on estrous cyclicity, ovarian morphology, serum hormone levels, and the HOMA-IR index. Key targets were identified through integrated metabolomics and bioinformatics analyses. The mechanism was further validated in vitro using dihydrotestosterone (DHT)-induced primary rat GCs, combined with molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, co-immunoprecipitation (CO-IP), and Seahorse metabolic analysis.
RESULTS: TLB administration alleviated estrous cycle disruption, improved ovarian morphology, and normalized serum testosterone, luteinizing hormone, and HOMA-IR index in PCOS rats. Metabolomics and bioinformatics analyses identified SIRT2 as a primary target of TLB. Mechanistically, TLB targets SIRT2, promoting the deacetylation of pyruvate kinase…
Read the paper
Related studies
- Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis
- Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules
- Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome
- Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome
- Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.