Dual Action of Myricetin on Porphyromonas gingivalis and the Inflammatory Response of Host Cells: A Promising Therapeutic Molecule for Periodontal Diseases

Periodontitis that affects the underlying structures of the periodontium, including the alveolar bone, is a multifactorial disease, whose etiology involves interactions between specific bacterial species of the subgingival biofilm and the host immune components. In the present study, we investigated the effects of myricetin, a flavonol largely distributed in fruits and vegetables, on growth and virulence properties of Porphyromonas gingivalis as well as on the P. gingivalis-induced inflammatory response in host cells. Minimal inhibitory concentration values of myricetin against P. gingivalis were in the range of 62.5 to 125 μg/ml. The iron-chelating activity of myricetin may contribute to the antibacterial activity of this flavonol. Myricetin was found to attenuate the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including proteinases (rgpA, rgpB, and kgp) and adhesins (fimA, hagA, and hagB). Myricetin dose-dependently prevented NF-κB activation in a monocyte model. Moreover, it inhibited the secretion of IL-6, IL-8 and MMP-3 by P. gingivalis-stimulated gingival fibroblasts. In conclusion, our study brought clear evidence that the flavonol myricetin exhibits a dual action on the periodontopathogenic bacterium P. gingivalis and the inflammatory response of host cells. Therefore, myricetin holds promise as a therapeutic agent for the treatment/prevention of periodontitis.

侵袭牙周组织（包括牙槽骨）内层结构的牙周炎是一种多因素疾病，其病因涉及龈下生物膜内特定菌种与宿主免疫成分之间的相互作用。本研究探究了广泛分布于果蔬中的黄酮醇（flavonol）类化合物杨梅素（myricetin）对牙龈卟啉单胞菌（Porphyromonas gingivalis）生长与毒力特性的影响，以及其对牙龈卟啉单胞菌诱导的宿主细胞炎症反应的调控作用。杨梅素对牙龈卟啉单胞菌的最低抑菌浓度（minimal inhibitory concentration, MIC）范围为62.5~125 μg/ml。杨梅素的铁螯合活性或许是该黄酮醇发挥抗菌作用的重要机制之一。研究发现，杨梅素可通过下调重要毒力因子编码基因的表达，减弱牙龈卟啉单胞菌的毒力，这些毒力因子包括蛋白酶（rgpA、rgpB及kgp）与黏附素（fimA、hagA及hagB）。杨梅素可在单核细胞模型中剂量依赖性地抑制核因子κB（NF-κB）的激活。此外，杨梅素可抑制牙龈卟啉单胞菌刺激的牙龈成纤维细胞分泌白细胞介素6（IL-6）、白细胞介素8（IL-8）及基质金属蛋白酶3（MMP-3）。综上，本研究明确证实，黄酮醇类化合物杨梅素可对牙周致病菌牙龈卟啉单胞菌及宿主细胞的炎症反应发挥双重调控作用。因此，杨梅素有望成为治疗或预防牙周炎的候选治疗药物。