Puerarin and DHEA combination therapy alleviates primary dysmenorrhea via inhibition of the Hsp90ab1/p38/JNK pathway

  • Mol Immunol. 2026 Jun:194:94-103. doi: 10.1016/j.molimm.2026.04.011.
Zhengquan Zhu  1 ,  Jianguo Ruan  2 ,  Ruizhe Wang  3 ,  Yihan Wang  3 ,  Haiyun Chen  3 ,  Xinye Yu  3 ,  Yanting Wen  4 ,  Yong Wang  5 ,  Daojuan Wang  6 ,  Gaojian Tao  7
Affiliations
  • 1. Department of Pain Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
  • 2. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • 3. State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
  • 4. State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: [email protected].
  • 6. Department of Pain Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: [email protected].
  • 7. Department of Pain Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: [email protected].
PMID: 42030694 DOI: 10.1016/j.molimm.2026.04.011
Abstract

Primary dysmenorrhea (PD), a prevalent gynecological disorder, is fundamentally driven by chronic uterine inflammation, leading to severe lower abdominal Pain and recurrent cramping. Given the known anti-inflammatory properties of Puerarin (Pue) and Dehydroepiandrosterone (DHEA), we investigated their individual and combined therapeutic effects on PD using an estradiol benzoate/oxytocin-induced mouse model. Our findings revealed that both Pue and DHEA alleviated PD symptoms, as evidenced by reduced writhing frequency, prolonged inter-writhe intervals, diminished uterine edema, lower uterine PGF2α/PGE2 ratio, decreased levels of inflammatory cytokines, and downregulated endometrial cyclooxygenase-2 (COX-2) expression. Notably, co-administration of Pue and DHEA produced superior therapeutic efficacy. Mechanistically, this combination more effectively reversed the pathological upregulation of Hsp90ab1 and the heightened phosphorylation of p38 and JNK in the PD uterus. However, lentiviral overexpression of Hsp90ab1 significantly attenuated the therapeutic benefits conferred by Pue and DHEA. Collectively, these results demonstrated that the synergistic action of Pue and DHEA represents a potent therapeutic strategy for PD, primarily through suppression of the Hsp90ab1/p38/JNK signaling and subsequent mitigation of uterine inflammation, offering a promising avenue for clinical intervention.

Keywords
DHEA; Hsp90ab1; Inflammation; Primary dysmenorrhea; Puerarin.
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