Curcumin regulates P2X7R level to inhibit TGF-β, NOX1, and MMP-3 expression in ox-LDL-treated macrophages

The role of P2X7R in promoting inflammation during atherosclerosis is well established; however, the effects of curcumin on P2X7R-related pathways remain poorly understood. This study investigates how curcumin affects P2X7R and related targets like NOX1, MMP-3, and TGF-β in ox-LDL-treated macrophages. THP-1-derived macrophages were exposed to 50 µg/mL oxidized low-density lipoprotein (ox-LDL) for 24 h to induce foam cell formation. Oil Red O staining was employed to confirm lipid accumulation and foam cell development. To investigate the modulatory effects, cells were exposed to P2X7R antagonist (A-438079) (100 µM) and curcumin (20, 40, and 60 µg/ml). The mRNA expression levels of P2RX7, NOX1, MMP-3, and TGF-β was evaluated using quantitative real-time PCR (RT-qPCR). Treatment induced macrophages with curcumin significantly reduced foam cell foemation, in a dose-dependent manner (P < 0.01). The mRNA expression levels of P2RX7, NOX1, MMP-3, and TGF-β were markedly upregulated in ox-LDL-treated macrophages compared to control, but significantly downregulated after treatment with curcumin (P < 0.05, P < 0.01). Similarly, treatment with selective P2X7R antagonist reduced foam cell foemation and suppressed the expression of NOX1, MMP-3, and TGF-β, thereby confirming the critical role of P2X7R in the atherogenic process development. Collectively, The present study demonstrates that curcumin exerts its anti-atherosclerotic effects primarily by inhibiting the P2X7R-mediated inflammatory pathway in ox-LDL-treated macrophages. These findings underscore curcumin's promising therapeutic potential as a natural agent for the prevention and treatment of atherosclerosis, warranting further investigation in preclinical and clinical settings.