Anti-fibrotic and anti-inflammatory properties of melatonin on human gingival fibroblasts in vitro.

Melatonin (MEL) has been proposed as a therapeutic agent for the oral cavity, due to its antioxidant and anti-inflammatory effects since periodontal diseases are aggravated by free radicals, and by disproportionate immunological response to plaque microorganism. In addition, MEL promotes bone formation. This study aimed to investigate the effects of MEL and 5-methoxytryptophol (5-MTX), an indole derivative related to MEL, on the growth rate of Staphylococcus epidermidis and on human gingival fibroblasts (HGF) for potential use in periodontal applications. HGF were treated with MEL and 5-MTX and the effects were evaluated on cell viability, gene expression, collagen production, wound healing and matrix metalloproteinase-1/tissue inhibitor of metalloproteinases-1 (MMP1/TIMP1) production. MEL showed the most promising biological effects in relation to periodontal applications. Thus, MEL was not toxic for HGF, increased collagen IIIα1, decorin and IL10, it down-regulated the expression of pro-fibrotic markers during wound healing, decreased the MMP1/TIMP1protein ratio. These results suggest that MEL could contribute to protect and recover the integrity of gingival tissues, thus, displaying a potential use for periodontal disease treatment or to functionalize dental implant abutments to improve soft tissue integration.