Faculty of Dentistry, National University of Singapore, Singapore, Singapore.
National Dental Centre, Singapore, Singapore.
Sci Rep. 2020 Jun 3;10(1):9072. doi: 10.1038/s41598-020-66031-8.
Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis. However, its inferior pharmacokinetics and toxicity concerns about its commonly used solvent dimethyl sulfoxide (DMSO) hinder translation to clinical applicability. Our study aimed to investigate the comparative antimicrobial properties of RES and its analogues (pterostilbene [PTS], oxyresveratrol [OXY] and piceatannol [PIC]), utilizing 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a solubiliser, which has a well-documented safety profile and FDA approval. These properties were investigated against Fusobacterium nucleatum, a key periodontal pathogen. PTS demonstrated the most potent antibacterial effects in HPβCD, with MIC > 60-fold lower than that of RES, OXY and PIC. In addition, PTS inhibited F. nucleatum biofilm formation. PTS exerted antimicrobial effects by eliciting leakage of cellular contents, leading to loss of bacterial cell viability. PTS also conferred immunomodulatory effects on F. nucleatum-challenged macrophages via upregulation of antioxidant pathways and inhibition of NF-κB activation. Given the superior antimicrobial potency of PTS against F. nucleatum compared to RES and other analogues, and coupled with its immunomodulatory properties, PTS complexed with HPβCD holds promise as a candidate nutraceutical for the adjunctive treatment of periodontitis.
白藜芦醇（RES）是一种天然多酚，具有作为牙周炎辅助治疗方法的潜力。然而，其较差的药代动力学和对其常用溶剂二甲基亚砜（DMSO）的毒性问题，阻碍了其向临床应用的转化。我们的研究旨在研究 RES 及其类似物（紫檀芪[PTS]、氧白藜芦醇[OXY]和白皮素[PIC]）的比较抗菌特性，利用 2-羟丙基-β-环糊精（HPβCD）作为增溶剂，HPβCD 具有良好的安全性和 FDA 批准。这些特性针对牙周病的关键病原体福赛斯坦纳菌进行了研究。紫檀芪在 HPβCD 中表现出最强的抗菌作用，其 MIC 比 RES、OXY 和 PIC 高 60 多倍。此外，紫檀芪抑制了 F. nucleatum 生物膜的形成。紫檀芪通过引发细胞内容物泄漏发挥抗菌作用，导致细菌细胞活力丧失。紫檀芪还通过上调抗氧化途径和抑制 NF-κB 激活对 F. nucleatum 挑战的巨噬细胞发挥免疫调节作用。鉴于 PTS 对 F. nucleatum 的抗菌效力优于 RES 和其他类似物，再加上其免疫调节特性，与 HPβCD 结合的 PTS 有望成为牙周炎辅助治疗的候选营养保健品。
