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Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis

Abstract

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4′,6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid–Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

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Funding

This study was funded by National Natural Science Foundation of China (31972171, 31671944, 31570028), Six Talent Peaks Project of Jiangsu Province (SWYY-026), Qing Lan Project of Jiangsu Province, Natural Science Foundation by Xuzhou City (KC17053), Jiangsu Science and Technology Agency Project (BK20141148) and the PAPD of Jiangsu Higher Education Institutions.

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JT and XP designed the experiments. LC, ZW, and LL performed the experiments. SQ and YM analyzed the data. LC and YL drafted the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xue Peng, Yong-xin Li or Jun Tian.

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All animal or human experiments in this study were performed in strict accordance with the Guide for the Care and Use of Chinese legislation, the Ministry of Science and Technology of China and were approved by the Institutional Jiangsu Normal University Committee for Animal Experiments.

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The authors declare that they have no competing interests.

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Chen, L., Wang, Z., Liu, L. et al. Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis. Appl Microbiol Biotechnol 103, 9037–9055 (2019). https://doi.org/10.1007/s00253-019-10119-3

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  • DOI: https://doi.org/10.1007/s00253-019-10119-3

Keywords

  • Candida albicans
  • Cinnamaldehyde
  • Reactive oxygen species
  • Apoptosis
  • Vulvovaginal candidiasis
  • Oropharyngeal candidiasis