Melatonin ameliorates TNFα-induced oral epithelial cell inflammation via Keap1-Nrf2 axis modulation

Oral mucosal inflammatory diseases comprise a diverse array of conditions that affect the delicate tissues lining the oral cavity, posing a multifaceted challenge in clinical practice. Further studies are needed to elucidate the pathogenesis of these conditions. Melatonin has emerged as a promising antioxidant that scavenges free radicals and attenuates oxidative stress, a key contributor to inflammatory processes.

This study employed two oral epithelial cell lines, human oral epithelial cells (HOEC) and human oral keratinocytes (HOK), alongside a three-dimensional (3D) epithelial cell model, to investigate the effects of melatonin on oral epithelial inflammation.

The findings revealed that TNFα significantly induced inflammation in oral epithelial cells, whereas melatonin inhibited TNFα-induced inflammation. Furthermore, melatonin's action in mitigating inflammation in oral epithelial cells was mediated via its receptor, MTNR1A. Mechanistically, melatonin suppressed inflammation in oral epithelial cells through the Keap1/Nrf2 signaling pathway. Additionally, melatonin attenuated TNFα-induced inflammation in the 3D oral epithelial cell model.

These findings offer novel insights into the potential development of therapies for treating oral epithelial inflammation.