1887

Abstract

Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of .

Anthraquinones and antifungals are associated with preventing biofilm formation and disrupting these communities. Antraquinones reduced the pathogenicity in the model.

This study aimed to evaluate the interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of .

Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. pathogenicity was investigated using the nematode . Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.

Anthraquinone–antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against biofilms. The mortality rate reached 76.7 % after the worms were exposed to for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to and these compounds at same time.

These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.

Keyword(s): anthraquinones , biofilm and nematode
Funding
This study was supported by the:
  • CNPq (Award 405312/2021-0, 305924/2021-4, 428737/2018-8 and 305036/2017-3)
    • Principle Award Recipient: MarcosFábio Gadelha Rocha
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/content/journal/jmm/10.1099/jmm.0.001815
2024-03-26
2024-04-27
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References

  1. Martinez LR, Casadevall A. Biofilm formation by Cryptococcus neoformans. Microbiol Spectr 2015; 3: [View Article] [PubMed]
    [Google Scholar]
  2. Camacho E, Casadevall A. Cryptococcal traits mediating adherence to biotic and abiotic surfaces. J Fungi 2018; 4:88 [View Article]
    [Google Scholar]
  3. Brilhante RSN, Araújo GDS, Fonseca XMQC, Guedes GM de M, Aguiar L de et al. Antifungal effect of anthraquinones against Cryptococcus neoformans: detection of synergism with amphotericin B. Med Mycol 2020myaa081 [View Article] [PubMed]
    [Google Scholar]
  4. Friedman M, Xu A, Lee R, Nguyen DN, Phan TA et al. The inhibitory activity of anthraquinones against pathogenic protozoa, bacteria, and fungi and the relationship to structure. Molecules 2020; 25:3101 [View Article] [PubMed]
    [Google Scholar]
  5. Salehi B, Albayrak S, Antolak H, Kręgiel D, Pawlikowska E et al. Aloe genus plants: from farm to food applications and phytopharmacotherapy. Int J Mol Sci 2018; 19:3390 [View Article] [PubMed]
    [Google Scholar]
  6. Sánchez M, González-Burgos E, Iglesias I, Gómez-Serranillos MP. Pharmacological update properties of Aloe vera and its major active constituents. Molecules 2020; 25:1324 [View Article] [PubMed]
    [Google Scholar]
  7. Dong X, Zeng Y, Liu Y, You L, Yin X et al. Aloe-emodin: a review of its pharmacology, toxicity, and pharmacokinetics. Phytother Res 2020; 34:270–281 [View Article] [PubMed]
    [Google Scholar]
  8. Lee W, Jeong G-S, Baek M-C, Ku S-K, Bae J-S. Renal protective effects of aloin in a mouse model of sepsis. Food Chem Toxicol 2019; 132:110651 [View Article] [PubMed]
    [Google Scholar]
  9. Chen Y, Feng B, Yuan Y, Hu J, Zhao W et al. Aloe emodin reduces cardiac inflammation induced by a high-fat diet through the TLR4 signaling pathway. Mediators Inflamm 2020; 2020:6318520 [View Article] [PubMed]
    [Google Scholar]
  10. Jiang X, Liu Y, Zhang G, Lin S, Wu J et al. Aloe-emodin induces breast tumor cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2. Evid Based Complement Alternat Med 2020; 2020:5108298 [View Article] [PubMed]
    [Google Scholar]
  11. Ma W, Liu C, Li J, Hao M, Ji Y et al. The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans. Photochem Photobiol Sci 2020; 19:485–494 [View Article] [PubMed]
    [Google Scholar]
  12. Xie L, Tang H, Song J, Long J, Zhang L et al. Chrysophanol: a review of its pharmacology, toxicity and pharmacokinetics. J Pharm Pharmacol 2019; 71:1475–1487 [View Article] [PubMed]
    [Google Scholar]
  13. Su S, Wu J, Gao Y, Luo Y, Yang D et al. The pharmacological properties of chrysophanol, the recent advances. Biomed Pharmacother 2020; 125:110002 [View Article] [PubMed]
    [Google Scholar]
  14. de Souza Collares Maia Castelo-Branco D, Dos Santos Araújo G, Fonseca XMQC, de Melo Guedes GM, da Rocha MG et al. Anthraquinones from Aloe spp. inhibit Cryptococcus neoformans sensu stricto: effects against growing and mature biofilms. Biofouling 2021; 37:809–817 [View Article] [PubMed]
    [Google Scholar]
  15. Brilhante RSN, Silva JAT, Araújo GDS, Pereira VS, Gotay WJP et al. Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs. J Med Microbiol 2020; 69:830–837 [View Article] [PubMed]
    [Google Scholar]
  16. Brilhante RSN, Oliveira JS de, Evangelista AJ de J, Serpa R, Silva AL da et al. Candida tropicalis from veterinary and human sources shows similar in vitro hemolytic activity, antifungal biofilm susceptibility and pathogenesis against Caenorhabditis elegans. Vet Microbiol 2016; 192:213–219 [View Article] [PubMed]
    [Google Scholar]
  17. Collins TJ. ImageJ for microscopy. BioTechniques 2007; 43:S25–S30 [View Article]
    [Google Scholar]
  18. Castelo-Branco D, Aguiar L, Araujo GS et al. In vitro and ex vivo biofilms of dermatophytes: a new panorama for the study of antifungal drugs. Biofouling 2020; 36:783–791 [View Article] [PubMed]
    [Google Scholar]
  19. Samrot AV, Abubakar Mohamed A, Faradjeva E, Si Jie L, Hooi Sze C et al. Mechanisms and impact of biofilms and targeting of biofilms using bioactive compounds-a review. Medicina (Kaunas) 2021; 57:839 [View Article] [PubMed]
    [Google Scholar]
  20. Rossato L, Loreto ES, Venturini TP, Azevedo MI, Al-Hatmi AMS et al. In vitro evaluation of antifungal combination against Cryptococcus neoformans. Diagn Microbiol Infect Dis 2019; 94:155–156 [View Article] [PubMed]
    [Google Scholar]
  21. Cheng G, Pi Z, Zhuang X, Zheng Z, Liu S et al. The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells. Phytother Res 2021; 35:3886–3897 [View Article] [PubMed]
    [Google Scholar]
  22. Ali MY, Park S, Chang M. Phytochemistry, ethnopharmacological uses, biological activities, and therapeutic applications of Cassia obtusifolia L.: a comprehensive review. Molecules 2021; 26:6252 [View Article] [PubMed]
    [Google Scholar]
  23. Liu Y, Mapa MST, Sprando RL. Anthraquinones inhibit cytochromes P450 enzyme activity in silico and in vitro. J of Applied Toxicology 2021; 41:1438–1445 [View Article]
    [Google Scholar]
  24. Birari L, Wagh S, Patil KR, Mahajan UB, Unger B et al. Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines. Cancer Chemother Pharmacol 2020; 86:419–426 [View Article] [PubMed]
    [Google Scholar]
  25. Bhimaneni S, Kumar A. Abscisic acid and aloe-emodin against NS2B-NS3A protease of Japanese encephalitis virus. Environ Sci Pollut Res Int 2022; 29:8759–8766 [View Article] [PubMed]
    [Google Scholar]
  26. Das A, Suresh Kumar G, Dutta S. Interaction of aloe active compounds with calf thymus DNA. J Mol Recognit 2019; 32:e2786 [View Article] [PubMed]
    [Google Scholar]
  27. Hu Y, Huang W, Luo Y, Xiang L, Wu J et al. Assessment of the anti-inflammatory effects of three rhubarb anthraquinones in LPS-Stimulated RAW264.7 macrophages using a pharmacodynamic model and evaluation of the structure-activity relationships. J Ethnopharmacol 2021; 273:114027 [View Article] [PubMed]
    [Google Scholar]
  28. Froldi G, Baronchelli F, Marin E, Grison M. Antiglycation activity and HT-29 cellular uptake of aloe-emodin, aloin, and Aloe arborescens leaf extracts. Molecules 2019; 24:2128 [View Article] [PubMed]
    [Google Scholar]
  29. Nivoix Y, Ledoux MP, Herbrecht R. Antifungal therapy: new and evolving therapies. Semin Respir Crit Care Med 2020; 41:158–174 [View Article] [PubMed]
    [Google Scholar]
  30. Kumari P, Arora N, Chatrath A, Gangwar R, Pruthi V et al. Delineating the biofilm inhibition mechanisms of phenolic and aldehydic terpenes against Cryptococcus neoformans. ACS Omega 2019; 4:17634–17648 [View Article] [PubMed]
    [Google Scholar]
  31. Mylonakis E, Ausubel FM, Perfect JR, Heitman J, Calderwood SB. Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis. Proc Natl Acad Sci U S A 2002; 99:15675–15680 [View Article] [PubMed]
    [Google Scholar]
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