Journal of Applied Oral Science · 2026
Metformin alleviates LPS-induced inflammation via suppression of the MAPK/AP-1 pathway in human dental pulp cells
By Park SY, Kim WJ, Park HS et al.
Objective Metformin, a first-line antidiabetic drug, has been increasingly recognized for its anti-inflammatory actions beyond glycemic control. This study investigated whether metformin modulates lipopolysaccharide (LPS)-induced inflammatory responses in human dental pulp cells (HDPCs) and explored the underlying signaling mechanisms. Methodology In HDPCs stimulated with Escherichia coli LPS in the presence or absence of metformin, cell viability, inflammatory mediator expression, mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling, and autophagy-related LC3 conversion were examined. Results Metformin and LPS treatment did not significantly affect HDPC viability at the tested concentrations. LPS stimulation increased the expression of pro-inflammatory mediators, including interleukin-6 and cyclooxygenase-2, whereas metformin significantly attenuated these responses. Mechanistically, metformin suppressed LPS-induced phosphorylation of p38, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and AP-1. Pharmacological inhibition of MAPK signaling also reduced AP-1 phosphorylation and interleukin-6 expression in LPS-stimulated HDPCs, supporting the involvement of MAPK-dependent AP-1 activation in the inflammatory response. Additionally, LPS enhanced LC3-I to LC3-II conversion, whereas metformin attenuated this autophagy-associated response. Conclusion These findings suggest that metformin attenuates LPS-induced inflammatory responses in HDPCs, at least in part, by suppressing MAPK/AP-1 signaling and modulating autophagy-associated signaling. Metformin may therefore have biological relevance as a host-modulatory agent in pulpal inflammation.