Ge-Gen Decoction Modulates the HSP90/AKT Signaling Pathway and the NLRP3 Inflammasome to Alleviate Primary Dysmenorrhea.

Objective: Ge-Gen Decoction (GGD) is a traditional Chinese medicinal formula composed of seven herbs (including Methods: Female Wistar rats were subjected to cold stimulation plus estradiol benzoate and oxytocin to establish a PDM model. Rats were divided into five groups (n = 6 each): control, PDM model, GGD (1.8 g/kg), GGD plus Terazosin (an HSP90 agonist, 0.08 g/kg), and ibuprofen (0.06 g/kg). Treatments were given orally once daily. PDM severity was assessed by writhing frequency and latency. Uterine histopathology, serum prostaglandins (PGE2, PGF2α) and inflammatory cytokines (IL-1β, IL-18, IL-6) were measured. Uterine expression of HSP90, p-AKT, NLRP3, Caspase-1, and IL-1β was examined by immunohistochemistry. Results: Compared to controls, the model group showed increased writhing frequency, elevated PGF2α and PGF2α/PGE2 ratio, severe uterine damage, and upregulation of HSP90, p-AKT, NLRP3, Caspase-1, and IL-1β. GGD treatment significantly attenuated all these changes, with effects comparable to ibuprofen. Notably, co-administration of Terazosin (HSP90 inhibitor) reversed the protective effects of GGD. GGD also reduced serum IL-1β, IL-18, and IL-6, and this suppression was antagonized by Terazosin. Conclusion: GGD alleviates cold-damp stagnation-type PDM in a rat model. The findings suggest that its mechanism involves modulation of the HSP90/AKT pathway, thereby suppressing NLRP3 inflammasome activation and subsequent pro-inflammatory cytokine release.