2. Academic Validation
  3. Enhancement of endometrial receptivity by Bushen Zhuyun Decoction via cryptotanshinone-mediated TRIM28 induction and HIF-1α suppression

Enhancement of endometrial receptivity by Bushen Zhuyun Decoction via cryptotanshinone-mediated TRIM28 induction and HIF-1α suppression

  • J Ethnopharmacol. 2025 Jun 26:350:119943. doi: 10.1016/j.jep.2025.119943.
Xingran Tang 1,  Huijin Zhao 1,  Yinyin Ding 2,  Yajie Qin 1,  Xiaotian Yang 1,  Xiaoyue Jiang 1,  Huifang Zhou 3,  Bei Liu 4
Affiliations

Affiliations

  • 1 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
  • 3 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address: yfy0005@njucm.edu.cn.
  • 4 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address: 956030454@qq.com.
PMID: 40449692 DOI: 10.1016/j.jep.2025.119943
Abstract

Ethnopharmacological relevance: Bushen Zhuyun Decoction (BSZYD), a traditional Chinese remedy, has demonstrated clinical efficacy in the treatment of luteal phase deficiency (LPD), though its mechanistic pathways remain largely undefined.

Aim of the study: This study aims to elucidate the mechanism by which BSZYD enhances endometrial receptivity.

Materials and methods: In an LPD rat model induced by RU-486 and treated with BSZYD, molecular markers of endometrial receptivity were evaluated using scanning electron microscopy (SEM). Furthermore, these markers were analyzed in the RL95-2 human adenocarcinoma cell line following knockdown of Tripartite motif containing 28 (TRIM28). Network pharmacology and UPLC-MS/MS were utilized to identify bioactive components that modulate Hypoxia-inducible factor-1 (HIF-1) signaling, followed by validation through molecular docking. The interaction between HIF-1α and TRIM28 was assessed using co-immunoprecipitation (Co-IP) and confocal microscopy. The effect of cryptotanshinone on TRIM28 expression was also examined in RL95-2 cells.

Results: BSZYD significantly increased the number of embryo implantation sites and reduced endometrial Reactive Oxygen Species (ROS) levels in LPD rats. TRIM28 was found to be crucial for BSZYD's enhancement of endometrial receptivity. Cryptotanshinone, a key component of BSZYD, downregulated HIF-1α expression in RL95-2 cells. The interaction between HIF-1α and TRIM28 was confirmed both in vivo and in vitro. In vitro, cryptotanshinone mitigated H2O2-induced oxidative stress. Furthermore, HIF-1α agonist administration attenuated BSZYD's ability to induce TRIM28 expression.

Conclusions: BSZYD and its bioactive constituent, cryptotanshinone, promote endometrial receptivity by inhibiting HIF-1α and upregulating TRIM28. These findings offer novel molecular targets and pharmacological insights for the prevention and treatment of LPD.

Keywords

Bushen Zhuyun Decoction (BSZYD); Cryptotanshinone; Endometrial receptivity; Luteal phase deficiency; TRIM28.

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