In this study, we explored the therapeutic efficacy of curcumin in PCOS treatment. By employing various conventional indicators such as pathological examination, weight loss, improvement of insulin resistance (IR), and normalization of abnormal hormone levels, we established that curcumin possesses the potential to ameliorate PCOS symptoms, consistent with prior research findings24,25,26,27,28,29. Our intervention demonstrated promising preventive and therapeutic effects, suggesting a viable avenue for PCOS management. Further investigations unveiled a potential correlation between the improvement of PCOS phenotype and the reduction of intestinal mucosal permeability, along with the inhibition of the TLR4/MyD88/NF-κB signaling pathway.
Evidence from multiple studies has underscored the involvement of chronic inflammation in the etiology and progression of PCOS, characterized by elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines30,32. Notably, aberrant levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-17A in plasma and follicular fluid have been associated with poor oocyte quality and compromised reproductive outcomes30,31,33. Our study revealed that curcumin treatment significantly decreased the levels of these pro-inflammatory cytokines while concurrently increasing the levels of anti-inflammatory cytokine IL-10, suggesting its potential in attenuating ovarian inflammation by modulating cytokine profiles.
Emerging research on the intestinal microbiota has implicated gut dysbiosis in PCOS pathogenesis, leading to compromised intestinal mucosal barrier integrity and heightened mucosal permeability 6, 34, 35. This disruption allows the translocation of lipopolysaccharide (LPS), derived from Gram-negative bacteria, into the bloodstream, triggering systemic low-grade inflammation and subsequent ovarian inflammation11, 12,36. Our findings demonstrated marked colonic tissue pathology in the PCOS model group, accompanied by decreased expression of tight junction proteins (ZO-1, Occludin) and elevated plasma LPS levels. Remarkably, curcumin intervention ameliorated colonic pathological damage, increased tight junction protein expression, and reduced plasma LPS levels, suggesting its potential in restoring intestinal mucosal barrier function and mitigating endotoxemia in PCOS.
Activation of the TLR4/MyD88/NF-κB signaling pathway is pivotal in mediating inflammatory responses, particularly in PCOS13,37,38, where it exacerbates insulin resistance15,16. Our study demonstrated that curcumin intervention downregulated the expression levels of TLR4, MyD88, and NF-κB p65 in ovarian tissue, indicating its potential in attenuating the inflammatory cascade and improving insulin resistance in PCOS.