Glycyrrhizic acid suppresses inflammation and reduces the increased glucose levels induced by the combination of Porphyromonas gulae and ligature placement in diabetic model mice
Glycyrrhizic acid suppresses inflammation and reduces the increased glucose levels induced by the combination of Porphyromonas gulae and ligature placement in diabetic model mice
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DOI：
10.1016/j.intimp.2018.12.045
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Kurihara, Hidemi
中科院分区：
文献类型：
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作者：
Akutagawa, Keiichi;Fujita, Tsuyoshi;Kurihara, Hidemi
糖尿病患者患严重和进行性牙周炎的风险增加。牙周病还通过增强胰岛素抵抗增加糖尿病的严重程度。因此，调节糖尿病患者的牙周炎症可能有助于控制这两种疾病。甘草酸通过抑制高迁移率族蛋白1（HMGB 1）发挥抗炎作用。HMGB 1是晚期糖基化终末产物受体（receptor for advanced glycation end products，HMGB 1）的配体之一，是一种损伤相关的分子模式，并诱导炎性细胞因子的产生。在本研究中，我们研究了烟酸对结扎和Gulae卟啉单胞菌感染诱导的牙周炎以及糖尿病模型小鼠中HMGB 1-β轴的参与的影响。通过将HFD 32喂养给ICK/TaJcl小鼠建立糖尿病模型小鼠的磨牙进行丝线结扎，然后在存在或不存在烟酸的情况下口内施用Gulae卟啉单胞菌。局部应用烟酸在牙龈中的mRNA水平和血清中的蛋白质水平上抑制结扎/古莱氏疟原虫诱导的白细胞介素（IL）-6和肿瘤坏死因子（TNE）-α的增加。此外，胡萝卜酸抑制结扎/P. gulae诱导的血清淀粉样蛋白A（SAA）的血清和空腹血糖水平的增加。它还在牙龈中的mRNA水平和血清中的蛋白水平上抑制结扎/古莱氏杆菌诱导的HMGB 1和HMGB 2的增加。小鼠抗HMGB 1中和抗体抑制血清葡萄糖水平的增加。总之，局部治疗与烟酸可以抑制牙周和全身炎症，并降低血糖水平，通过HMGB 1-β轴糖尿病小鼠。
Diabetic patients are at an increased risk of developing severe and progressive periodontitis. Periodontal disease also increases the severity of diabetes by enhancing insulin resistance. Therefore, the regulation of periodontal inflammation in diabetic patients may contribute to the control of both diseases. Glycyrrhizic acid exerts anti-inflammatory effects by inhibiting high mobility group box 1 (HMGB1). HMGB1, one of the ligands of the receptor for advanced glycation end products (RAGE), is a damage-associated molecular pattern and induces inflammatory cytokine production. In the present study, we examined the effects of glycyrrhizic acid on ligature-and Porphyromonas gulae infection-induced periodontitis as well as the involvement of the HMGB1-RAGE axis in diabetic model mice.The molars of diabetic model mice, established by feeding HFD32 to ICK/TaJcl mice, were subjected to silk thread ligation and P. gulae was then intraorally applied in the presence or absence of glycyrrhizic acid given topically. The topical application of glycyrrhizic acid suppressed ligature/P. gulae-induced increases in interleukin (IL)-6 and tumor necrosis factor (TNE)-alpha at the mRNA level in the gingiva and at the protein level in serum. Furthermore, glycyrrhizic acid suppressed ligature/P. gulae-induced increases in serum amyloid A (SAA) in serum and fasting blood glucose levels. It also suppressed ligature/P. gulae-induced increases of HMGB1 and RAGE at the mRNA level in the gingiva and at the protein level in serum. A mouse anti-HMGB1-neutralizing antibody inhibited increases in serum glucose levels. In conclusion, topical treatments with glycyrrhizic acid may suppress periodontal and systemic inflammation and reduce blood glucose levels through the HMGB1-RAGE axis in diabetic mice.