Curcumin Alleviates HMGB1-Mediated Inflammation Through the Signaling Pathway of TLR2-NF-κB in Bovine Ovarian Granulosa Cells

Curcumin, the principal bioactive compound derived from turmeric, possesses a wide range of therapeutic properties such as anti-inflammatory, antioxidant, and wound-healing properties. Recent studies suggest that curcumin may alleviate HMGB1-mediated inflammation in ovarian cells. However, its role in modulating dysfunction in HMGB1-driven ovarian granulosa cells (OGCs) remains to be elucidated. In the present study, curcumin suppresses the HMGB1-induced overexpression of toll-like receptor 2 (<i>TLR2</i>) and ovulation-related factors such as <i>EGFR</i>, <i>VEGF</i>, <i>STAR</i>, and <i>TIMP1/2</i> genes. Additionally, the elevated levels of <i>TLR2</i>, <i>TLR1</i>, <i>TLR6</i>, and phospho-NF-κB p65 proteins were significantly inhibited by curcumin. Further mechanistic analysis reveals that the interaction between HMGB1 and the <i>TLR1</i>-<i>TLR2</i>/<i>TLR6</i> complex, as well as phospho-NF-κB p65, was restrained. This resulted in the suppression of the pro-inflammatory cytokine IL-6 production and the alleviation of the HMGB1-induced inflammation response in OGCs. Collectively, our findings demonstrate that curcumin modulates the upregulation of ovulation-related genes and pro-inflammatory cytokines in OGCs by inhibiting the <i>TLR2</i>-NF-κB pathway, providing a mechanistic basis for its potential application as a therapeutic agent against OGC inflammation.