SIRT6 activator MDL-800 alleviates periodontal inflammation by inhibiting AIM2 pathway

. We noted that MDL-800 remarkably reduced expressions of pro-inflammatory cytokines in LPS-induced HGFs, which was neutralized by inhibiting SIRT6. Besides, MDL-800 could also reduce oxidative stress damage under inflammatory conditions. The suppression of AIM2 inflammasome activation was associated with the significant anti-inflammatory properties of MDL-800, as demonstrated by RNA sequencing and validation experiments. In conclusion, these findings suggest that MDL-800 was effective in reducing periodontal inflammation, partly by inhibiting AIM2 pathway in a SIRT6-dependent manner, demonstrating significant promise for enhancing therapeutic outcomes in periodontitis.