Anti-Inflammatory Effects of Geniposidic Acid on Porphyromonas gingivalis-Induced Periodontitis in Mice

Tetsuya Tamura; Ruoqi Zhai; Tasuku Takemura; Kazuhisa Ouhara; Yuri Taniguchi; Yuta Hamamoto; Ryousuke Fujimori; Mikihito Kajiya; Shinji Matsuda; Syuichi Munenaga; Tsuyoshi Fujita; Noriyoshi Mizuno

doi:10.3390/biomedicines10123096

Anti-Inflammatory Effects of Geniposidic Acid on Porphyromonas gingivalis-Induced Periodontitis in Mice

Biomedicines. 2022 Dec 1;10(12):3096. doi: 10.3390/biomedicines10123096.

Affiliations

¹ Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
² Department of Innovation and Precision Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
³ Department of General Dentistry, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

Abstract

Periodontal disease is predominantly caused by the pathogenic bacterium Porphyromonas gingivalis that produces inflammation-inducing factors in the host. Eucommia ulmoides is a plant native to China that has been reported to reduce blood pressure, promote weight loss, and exhibit anti-inflammatory effects. Geniposidic acid (GPA) is the major component of E. ulmoides. Herein, we investigated the effects of GPA on P. gingivalis-induced periodontitis by measuring the inflammatory responses in human gingival epithelial cells (HGECs) after P. gingivalis stimulation and GPA addition in a P. gingivalis-induced periodontitis mouse model. We found that GPA addition suppressed interleukin (IL)-6 mRNA induction (33.8% suppression), IL-6 production (69.2% suppression), toll-like receptor (TLR) 2 induction, and mitogen-activated protein kinase (MAPK) phosphorylation in HGECs stimulated by P. gingivalis. Inoculation of mice with GPA inhibited P. gingivalis-induced alveolar bone resorption (25.6% suppression) by suppressing IL-6 and TLR2 production in the serum and gingiva. GPA suppressed osteoclast differentiation of bone marrow cells induced by M-CSF and sRANKL in mice (56.7% suppression). GPA also suppressed the mRNA expression of OSCAR, NFATc1, c-Fos, cathepsin K, and DC-STAMP. In summary, GPA exerts an anti-inflammatory effect on periodontal tissue and may be effective in preventing periodontal disease.

Keywords: Porphyromonas gingivalis; bone resorption; geniposidic acid; interleukin 6; mouse.

Grants and funding

This work was supported by a Grant-in-Aid for the Encouragement of Young Scientists (B) under Grants 19K18999, 22K17038, and Grant-in-Aid for Scientific Research (C) under Grants 18K09599, 22K09983 from the Japan Society for the Promotion of Science.