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

  • Tissue Cell. 2026 May 30:103:103657. doi: 10.1016/j.tice.2026.103657.
Lan Chen  1 ,  Dijun Wang  2 ,  Jiali Cai  2 ,  Li Zhu  2 ,  Xiaojing Yan  2 ,  Yuanpei Lian  2 ,  Shikang Zhou  2 ,  Chunyan Yin  2 ,  Ji Cao  2 ,  Xueke Nie  2 ,  Jiming Chen  3
Affiliations
  • 1. Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, Jiangsu 213003, China. Electronic address: [email protected].
  • 2. Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, Jiangsu 213003, China.
  • 3. Department of Gynecology, Changzhou Second People's Hospital, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China. Electronic address: [email protected].
PMID: 42288009 DOI: 10.1016/j.tice.2026.103657
Abstract

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.

Keywords
DingkunDɑn; Ovarian fibrosis; Polycystic ovary syndrome; TGF-β/Smad pathway.