Chia-Ming Liu1, Szu-Han Chen2, Yi-Wen Liao3, Chuan-Hang Yu1, Cheng-Chia Yu4, Pei-Ling Hsieh5. 1. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. 2. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. 3. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. 4. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: ccyu@csmu.edu.tw. 5. Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: plhsieh@mail.cmu.edu.tw.
Abstract
BACKGROUND/ PURPOSE: Periodontal disease and diabetes mellitus (DM) are both chronic inflammatory and highly prevalent diseases. A large amount of evidence suggested that the accumulation of oxidative stress plays a significant role in the deterioration of both diseases. Magnolol has been known to possess anti-inflammatory and anti-oxidant activities in various tissues, but its effects on gingival cells under diabetic conditions have not been fully understood. METHODS: We assessed the generation of reactive oxygen species (ROS), Transwell migration, and wound healing ability in response to the advanced glycation end products (AGEs) stimulation with or without Magnolol treatment. Subsequently, we examined the expression of Nrf2 and HO-1 to ascertain whether Magnolol was able to activate the anti-oxidant signaling. We also measured the secretion of IL-6 and IL-8, and conducted a knockdown experiment to elucidate the effect of Mrf2 on their secretion. RESULTS: The AGEs-induced ROS was dose-dependently downregulated following the Magnolol treatment. Likewise, the reduced Transwell migration and wound healing ability were improved by various concentrations of Magnolol. Results from qRT-PCR indicated that the suppression of Nrf2 and HO-1 following AGEs stimulation was reversed by Magnolol. Also, the AGEs-elicited production of IL-6 and IL-8 was inhibited by Magnolol. Moreover, our results demonstrated that this anti-inflammatory effect was mediated by the upregulation of Nrf2. CONCLUSION: These findings showed that excessive AGEs in the gingiva may lead to the accumulation of ROS and pro-inflammatory cytokines. Supplement of Magnolol may be beneficial to improve the impaired wound healing and inflammation by upregulation of Nrf2 signaling for DM patients with periodontal disease.
BACKGROUND/ PURPOSE:Periodontal disease and diabetes mellitus (DM) are both chronic inflammatory and highly prevalent diseases. A large amount of evidence suggested that the accumulation of oxidative stress plays a significant role in the deterioration of both diseases. Magnolol has been known to possess anti-inflammatory and anti-oxidant activities in various tissues, but its effects on gingival cells under diabetic conditions have not been fully understood. METHODS: We assessed the generation of reactive oxygen species (ROS), Transwell migration, and wound healing ability in response to the advanced glycation end products (AGEs) stimulation with or without Magnolol treatment. Subsequently, we examined the expression of Nrf2 and HO-1 to ascertain whether Magnolol was able to activate the anti-oxidant signaling. We also measured the secretion of IL-6 and IL-8, and conducted a knockdown experiment to elucidate the effect of Mrf2 on their secretion. RESULTS: The AGEs-induced ROS was dose-dependently downregulated following the Magnolol treatment. Likewise, the reduced Transwell migration and wound healing ability were improved by various concentrations of Magnolol. Results from qRT-PCR indicated that the suppression of Nrf2 and HO-1 following AGEs stimulation was reversed by Magnolol. Also, the AGEs-elicited production of IL-6 and IL-8 was inhibited by Magnolol. Moreover, our results demonstrated that this anti-inflammatory effect was mediated by the upregulation of Nrf2. CONCLUSION: These findings showed that excessive AGEs in the gingiva may lead to the accumulation of ROS and pro-inflammatory cytokines. Supplement of Magnolol may be beneficial to improve the impaired wound healing and inflammation by upregulation of Nrf2 signaling for DMpatients with periodontal disease.