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肉桂醛与氟化物和洗必泰联合作用对变异链球菌的影响。

Combinatorial effects of trans-cinnamaldehyde with fluoride and chlorhexidine on Streptococcus mutans.

机构信息

Quorum Sensing Laboratory, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, India.

Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.

出版信息

J Appl Microbiol. 2021 Feb;130(2):382-393. doi: 10.1111/jam.14794. Epub 2020 Aug 10.

DOI:10.1111/jam.14794
PMID:32707601
Abstract

AIMS

The aim of this study was to investigate the effects of trans-cinnamaldehyde (TC) and its synergistic activity with chlorhexidine (CHX) and fluoride against Streptococcus mutans.

METHODS AND RESULTS

Streptococcus mutans UA159 was treated with TC alone and in combination with CHX or sodium fluoride. The synergy profile was analysed using the Zero Interaction Potency model. TC showed strong synergism (synergy score of 21·697) with CHX, but additive effect (synergy score of 5·298) with fluoride. TC and the combinations were tested for acid production (glycolytic pH drop) and biofilm formation by S. mutans, and nitric oxide production in macrophages. TC significantly inhibited sucrose-dependent biofilm formation and acid production by S. mutans. Mechanistic studies were carried out by qRT-PCR-based transcriptomic studies which showed that TC acts by impairing genes related to metabolism, quorum sensing, bacteriocin expression, stress tolerance and biofilm formation.

CONCLUSIONS

trans-Cinnamaldehyde potentiates CHX and sodium fluoride in inhibiting S. mutans biofilms and virulence through multiple mechanisms. This study sheds significant new light on the potential to develop TC as an anti-caries treatment.

SIGNIFICANCE AND IMPACT OF THE STUDY

Oral diseases were classified as a 'silent epidemic' in the US Surgeon General's Report on Oral Health. Two decades later, >4 billion people are still affected worldwide by caries, having significant effects on the quality of life. There is an urgent need to develop novel compounds and strategies to combat dental caries. Here, we prove that TC downregulates multiple pathways and potentiates the CHX and fluoride to prevent S. mutans biofilms and virulence. This study sheds significant new light on the potential to develop TC in combination with CHX or fluoride as novel treatments to arrest dental caries.

摘要

目的

本研究旨在探讨肉桂醛(TC)及其与洗必泰(CHX)和氟化物协同作用对变异链球菌的影响。

方法和结果

单独及联合 CHX 或氟化钠处理变异链球菌 UA159。采用零相互作用潜能模型分析协同作用谱。TC 与 CHX 表现出强烈的协同作用(协同评分 21.697),与氟化物表现出相加作用(协同评分 5.298)。TC 及其组合用于检测变异链球菌的产酸(糖酵解 pH 下降)和生物膜形成以及巨噬细胞中一氧化氮的产生。TC 显著抑制蔗糖依赖性生物膜形成和变异链球菌产酸。基于 qRT-PCR 的转录组学研究表明,TC 通过损害与代谢、群体感应、细菌素表达、应激耐受和生物膜形成相关的基因起作用。

结论

肉桂醛通过多种机制增强 CHX 和氟化钠对变异链球菌生物膜和毒力的抑制作用。本研究为开发 TC 作为抗龋治疗提供了重要依据。

研究的意义和影响

美国外科医生报告将口腔疾病归类为“无声的流行”。二十年后,全世界仍有超过 40 亿人受到龋齿的影响,这对生活质量有重大影响。迫切需要开发新的化合物和策略来对抗龋齿。本研究证明 TC 下调多个途径,并增强 CHX 和氟化物以预防变异链球菌生物膜和毒力。这项研究为开发 TC 与 CHX 或氟化物联合作为预防龋齿的新型治疗方法提供了重要依据。

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