1. Academic Validation
  2. Antcin K suppresses proinflammatory cytokines expression via the PI3K, Akt and NF-κB pathways in human gingival fibroblasts: implications for periodontitis treatment

Antcin K suppresses proinflammatory cytokines expression via the PI3K, Akt and NF-κB pathways in human gingival fibroblasts: implications for periodontitis treatment

  • Cell Death Discov. 2025 Nov 22;12(1):25. doi: 10.1038/s41420-025-02865-3.
Ya-Hsin Wu 1 2 Yueh-Hsiung Kuo 3 4 Yen-You Lin 5 Tzong-Ming Shieh 1 Tzu-Ching Chang 6 An-Chen Chang 7 Ju-Fang Liu 8 Chih-Hsin Tang 9 10 11
Affiliations

Affiliations

  • 1 School of Dentistry, China Medical University, Taichung, Taiwan.
  • 2 Department of Periodontology, China Medical University Hospital, Taichung, Taiwan.
  • 3 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
  • 4 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
  • 5 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  • 6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
  • 7 School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan.
  • 8 School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan. [email protected].
  • 9 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan. [email protected].
  • 10 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. [email protected].
  • 11 Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. [email protected].
Abstract

Numerous inflammatory cytokines control the pathogenesis of periodontitis, an infectious Bacterial disease, via interacting with immune and tissue cells. Antrodia cinnamomea is the origin of the triterpenoid Antcin K, renowned for its immunomodulatory and anti-inflammatory properties. However, the therapeutic performances of Antcin K on periodontitis remain unclear. Lipopolysaccharide (LPS) is the primary virulence factor of Porphyromonas gingivalis, a common periodontal pathogen, which augments the synthesis of proinflammatory cytokines for instance IL-1β, IL-6, IL-8, and IL-17A in primary human gingival fibroblasts (HGFs). Interestingly, treatment of HGFs with Antcin K inhibited LPS-induced proinflammatory cytokines production. RNA Sequencing analysis indicated that the PI3K-Akt pathway is potentially linked in Antcin K's anti-inflammatory function. We revealed that the PI3K, Akt, and NF-κB pathways mediate Antcin K's suppression of proinflammatory cytokines production. Specifically, our in vivo study demonstrated that Antcin K blocks pathogenesis of periodontal disease in a ligature-mediated periodontitis model. Therefore, we suggest that Antcin K may be a potential therapeutic candidate for controlling periodontal disease.

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