Research and Development Headquarters, Earth Corporation, Ltd., Hyogo, 678-0192, Japan.
Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Odontology. 2021 Apr;109(2):464-473. doi: 10.1007/s10266-020-00563-3. Epub 2020 Nov 3.
Periodontal disease is the most prevalent infectious disease, and inflammatory mediators play critical roles in its progression. Therefore, controlling pro-inflammatory cytokine production, especially at initial disease stages, is essential to maintaining gingival and periodontal health. Glycyrrhizin (GL) has an anti-inflammatory effect and has been added to toothpaste and mouth rinse to prevent periodontal disease. However, there is a maximum dose for the use of GL. The aim of the present study is to screen plant extracts which can effectively enhance the effects of GL. The effects of extracts from six different plants on GL-suppressed TNF-α expression in Aggregatibacter actinomycetemcomitans (A.a.)-LPS-stimulated human oral keratinocytes (RT7) were examined. Results demonstrated that Equisetum arvense (EA) extract had the strongest additive effect on the suppression of TNF-α by GL at both mRNA and protein levels. In addition, GL downregulated the production of TNF-α by suppressing NF-κB p65 phosphorylation, but not JNK or p38 phosphorylation. In contrast, EA decreased JNK phosphorylation but not NF-κB p65 or p38 phosphorylation. The combination of GL and EA effectively attenuated A.a.-LPS-induced phosphorylation of NF-κB p65 and JNK. Furthermore, an LPS-induced periodontitis rat model showed that GL with EA supplementation significantly downregulated TNF-α mRNA in the gingival tissue. These results indicate that EA can suppress A.a.-LPS-induced pro-inflammatory cytokine production by inhibiting JNK activation and can promote the anti-inflammatory effects of GL. Our findings suggest that a combination of GL and EA may improve the development of new oral hygiene products aimed at enhancing periodontal health.
牙周病是最常见的传染病，炎症介质在其进展中起着关键作用。因此，控制促炎细胞因子的产生，尤其是在疾病早期阶段，对于维持牙龈和牙周健康至关重要。甘草酸（GL）具有抗炎作用，并已添加到牙膏和漱口水中以预防牙周病。但是，GL 的使用有最大剂量限制。本研究旨在筛选能够有效增强 GL 作用的植物提取物。研究了六种不同植物提取物对 GL 抑制的 A.a.-LPS 刺激的人口腔角质形成细胞（RT7）中 TNF-α表达的影响。结果表明，问荆（EA）提取物在 mRNA 和蛋白质水平上对 GL 抑制 TNF-α的作用具有最强的增效作用。此外，GL 通过抑制 NF-κB p65 磷酸化而不是 JNK 或 p38 磷酸化来下调 TNF-α的产生。相比之下，EA 降低了 JNK 磷酸化但不影响 NF-κB p65 或 p38 磷酸化。GL 和 EA 的组合可有效减轻 A.a.-LPS 诱导的 NF-κB p65 和 JNK 磷酸化。此外，LPS 诱导的牙周炎大鼠模型表明，GL 加 EA 补充可显著下调牙龈组织中 TNF-α mRNA 的表达。这些结果表明，EA 可以通过抑制 JNK 激活来抑制 A.a.-LPS 诱导的促炎细胞因子产生，并增强 GL 的抗炎作用。我们的研究结果表明，GL 和 EA 的组合可能有助于开发新的口腔卫生产品，以增强牙周健康。
