Taiwanese green propolis suppresses NLRP3 inflammasome activation and induces Nrf2/HO-1 pathway to reduce periodontal pathogen-induced endothelial inflammation

  • Arch Oral Biol. 2025 Oct:178:106364. doi: 10.1016/j.archoralbio.2025.106364.
Yi-Jen Lai  1 ,  Yin-Chu Chuang  2 ,  Yung-Li Wang  3 ,  Ming-Tse Li  3 ,  Emily Sunny Lee  3 ,  Wei-Ju Lee  4 ,  Wei-Ning Lin  5 ,  Yuh-Lien Chen  6 ,  Ching-Shuen Wang  3 ,  Thi Thuy Tien Vo  7 ,  Yue-Wen Chen  8 ,  I-Ta Lee  9
Affiliations
  • 1. Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
  • 2. Department of Chinese Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
  • 3. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
  • 4. School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
  • 5. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • 6. Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 7. Department of Pediatric Dentistry, Faculty of Dentistry, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam.
  • 8. Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan.
  • 9. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 40753822 DOI: 10.1016/j.archoralbio.2025.106364
Abstract

Objective: Periodontitis is a chronic inflammatory disease associated with systemic conditions, including cardiovascular diseases. Porphyromonas gingivalis (Pg), a key periodontal pathogen, contributes to vascular endothelial dysfunction through its virulence factors. This study aimed to investigate the protective effects of Taiwanese green propolis (TGP) against Pg-derived lipopolysaccharide (Pg-LPS)-induced endothelial inflammation, focusing on its modulation of the NLRP3 inflammasome and Nrf2/HO-1 signaling pathways.

Design: Human aortic endothelial cells (HAECs) were stimulated with Pg-LPS in the presence or absence of TGP. The expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) was assessed using Real-Time PCR and ELISA. ROS production was evaluated using fluorescence-based assays, while NF-κB activation and Nrf2 transcriptional activity were analyzed via luciferase reporter assays. Pharmacological inhibitors were used to confirm the involvement of these pathways.

Results: TGP significantly reduced Pg-LPS-induced IL-1β, TNF-α, and IL-6 expression in HAECs. It inhibited NF-κB activation, suppressed ROS generation, and attenuated NLRP3 inflammasome activation. Additionally, TGP upregulated HO-1 expression and enhanced Nrf2 transcriptional activity, as evidenced by ARE-driven luciferase reporter assays. Pharmacological inhibition of Nrf2 and HO-1 reversed TGP's anti-inflammatory effects, confirming that the Nrf2/HO-1 axis is critical for its protective function.

Conclusions: These findings demonstrate that TGP exerts anti-inflammatory and cytoprotective effects by suppressing NLRP3 inflammasome activation and enhancing the Nrf2/HO-1 pathway, reducing Pg-LPS-induced endothelial inflammation. This study suggests that TGP could be a promising natural therapeutic agent for mitigating periodontal pathogen-induced systemic inflammation.

Keywords
Inflammation; NLRP3 inflammasome; Oxidative stress; Porphyromonas gingivalis; Taiwanese green propolis.
Products