2. Academic Validation
  3. Gallic acid promotes M2 macrophage polarization through mitochondrial oxidative phosphorylation in periodontitis

Gallic acid promotes M2 macrophage polarization through mitochondrial oxidative phosphorylation in periodontitis

  • Arch Oral Biol. 2025 Mar 15:174:106237. doi: 10.1016/j.archoralbio.2025.106237.
Ruobing Zhang 1,  Wenjing Yang 2,  Kai Li 2,  Xiaolong Zhang 2,  Jie Liu 2,  Lin Ai 3
Affiliations

Affiliations

  • 1 Center for Drug Evaluation, Shaanxi Medical Products Administration, Xi'an, China.
  • 2 Xijing 986 Hospital Department, The Fourth Military Medical University, Xi'an, China.
  • 3 Xijing 986 Hospital Department, The Fourth Military Medical University, Xi'an, China. Electronic address: Alin19806154@163.com.
PMID: 40107001 DOI: 10.1016/j.archoralbio.2025.106237
Abstract

Objective: This in vitro investigation assessed the role of gallic acid in regulating macrophage polarization.

Design: In this study, RAW264.7 macrophages were treated with P. gingivalis lipopolysaccharide (LPS) to mimic inflammatory conditions in periodontitis. Immunofluorescence staining, enzyme‑linked immunosorbent (ELISA) assay, RNA Sequencing, and seahorse metabolic profile assay were used to assess the effects of gallic acid on macrophage polarization, cytokine release, underlying mechanism and metabolic profile.

Results: The study demonstrated that treatment with gallic acid could induce M2 polarization of macrophages (P < 0.01) and increase the production of anti-inflammatory cytokines (P < 0.01). Analysis of RNA Sequencing data showed enrichment of mitochondrial Oxidative Phosphorylation, regulation of metabolic processes, and the PI3K-Akt signaling pathway in LPS-treated macrophages treated with gallic acid. Furthermore, gallic acid was found to enhance mitochondrial Oxidative Phosphorylation activity through the PI3K-Akt signaling pathway in RAW264.7 cells.

Conclusions: Gallic acid treatment has the potential to promote M2 polarization of macrophages by modulating mitochondrial Oxidative Phosphorylation via the PI3K-Akt signaling pathway.

Keywords

Gallic acid; Macrophage; Mitochondria; Periodontitis.

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