Sesamin suppresses high glucose-induced cyclooxygenase-2 and prostaglandin E2 production through Toll-like receptor 2-dependent oxidative stress in human gingival fibroblasts

Authors

• Ya-Lun Li, Department of Applied Mathematics, National Chung Hsing University, Taichung, Taiwan
• Yu-Chia Hsu, Department of Agronomy, National Chiayi University, Chiayi, Taiwan
• Fang-Yu Fan, School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Yung-Li Wang, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Yang-Che Wu, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Sin-Yu Li, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
• Thi Thuy Tien Vo, Faculty of Dentistry, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam
• Yu-Chia Chang, Center for Drug Research and Development, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
• Yin-Tzer Shih, Department of Applied Mathematics, National Chung Hsing University, Taichung, Taiwan
• I-Ta Lee, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, TaiwanFollow

Abstract

Background/purpose: Hyperglycemia contributes to periodontal inflammation through oxidative stress and inflammatory mediator production in gingival fibroblasts. Sesamin, a major lignan from sesame, has antioxidant and anti-inflammatory properties. This study investigated whether sesamin attenuates high glucose (HG)-induced cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) production in human gingival fibroblasts (HGFs), and examined the involvement of Toll-like receptor 2 (TLR2)-dependent oxidative signaling.

Materials and methods: HGFs were exposed to HG in the presence or absence of sesamin. Cell viability, reactive oxygen species (ROS) generation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, COX-2 expression, and PGE₂ production were evaluated. The roles of TLR2, myeloid differentiation primary response 88 (MyD88), phosphoinositide 3-kinase (PI3K), Akt, and hypoxia-inducible factor-1a (HIF-1a) were examined using pathway-targeting approaches.

Results: HG increased TLR2 expression, enhanced NADPH oxidase-dependent ROS generation, and activated PI3K/Akt and HIF-1a signaling in HGFs. These responses were accompanied by increased COX-2 expression and PGE₂ production. Sesamin suppressed HG-induced ROS generation, NADPH oxidase activity, PI3K/Akt and HIF-1a activation, COX-2 upregulation, and PGE₂ release. Blockade of TLR2, MyD88, ROS generation, PI3K/Akt signaling, or HIF-1a also reduced HG-induced COX-2 expression and PGE₂ production, supporting a TLR2/MyD88-dependent oxidative mechanism. Overall, the data indicate that sesamin targets upstream receptor-associated oxidative events rather than only terminal prostaglandin production.

Conclusion: Sesamin attenuates HG-induced inflammatory responses in HGFs by suppressing TLR2/MyD88-mediated ROS generation and downstream PI3K/Akt/HIF-1a signaling. These findings suggest that sesamin may have potential as an adjunctive anti-inflammatory and antioxidant agent for modulating hyperglycemia-associated gingival inflammatory responses under diabetic-like conditions relevant to periodontal disease

Recommended Citation

Li, Ya-Lun; Hsu, Yu-Chia; Fan, Fang-Yu; Wang, Yung-Li; Wu, Yang-Che; Li, Sin-Yu; Vo, Thi Thuy Tien; Chang, Yu-Chia; Shih, Yin-Tzer; and Lee, I-Ta (2026) "Sesamin suppresses high glucose-induced cyclooxygenase-2 and prostaglandin E2 production through Toll-like receptor 2-dependent oxidative stress in human gingival fibroblasts," Journal of Dental Sciences: Vol. 21: Iss. 4, Article 24.
Available at: https://jds.ads.org.tw/journal/vol21/iss4/24

Publication Date

2026

Received Date

June 08 2026

Accepted Date

June 12 2026

Final Revision Date

June 12 2026