DingkunDɑn ameliorates ovarian fibrosis and restores ovulation in a DHEA-induced PCOS rat model via inhibition of the TGF-β/Smad signaling pathway.

BACKGROUND

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, and ovarian fibrosis is a key pathological basis for ovulatory dysfunction. Dingkun Dan (DKD), a classic Chinese herbal compound, has shown certain therapeutic effects on PCOS; however, whether it ameliorates ovarian fibrosis through inhibiting the TGF-β/Smad pathway remains unclear.

OBJECTIVE

To elucidate the mechanism by which DKD inhibits the TGF-β/Smad pathway to ameliorate ovarian fibrosis and restore ovulatory function in PCOS through in vivo and in vitro experiments.

METHODS

Female SD rats (SPF grade, 3 weeks old) were used to induce the PCOS model with dehydroepiandrosterone (DHEA). Rats received intragastric administration of Dingkun Dan (DKD) for 14 consecutive days via gavage at four dosage levels: vehicle control (distilled water), low dose (1.125 g/kg per day), medium dose (2.250 g/kg per day), and high dose (4.500 g/kg per day). Changes in ovarian pathological structures were recorded, and serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were measured. Granulosa cells (GCs)from PCOS rat ovaries were cultured to evaluate the effects of different doses of DKD on cell viability (CV), apoptosis, and the TGF-β1/Smad pathway.

RESULTS

DKD significantly improved ovarian cystic changes in PCOS rats, reduced serum levels of E2, LH, and T, increased FSH levels, and downregulated TGF-β1, Smad2, Smad3, I Collagen, III Collagen and α-SMA in ovarian tissue (OT) and GCs; The treatment promoted GCs survival and inhibited apoptosis (P<0.05).

CONCLUSION

DKD exerts its effects by inhibiting the activation of the TGF-β/Smad pathway, thereby ameliorating ovarian fibrosis, restoring endocrine balance and ovulatory function, providing new experimental evidence for the traditional Chinese medicine treatment of PCOS.