1887

Journal of Medical Microbiology logo

Volume 71, Issue 5

Evaluation of the antifungal effect of chlorogenic acid against strains of spp. resistant to fluconazole: apoptosis induction and analysis of the possible mechanisms of action No Access

Abstract

spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs.

With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary.

This study evaluated the antifungal activity of chlorogenic acid against fluconazole-resistant strains of spp.

Mechanism of action through flow cytometry and analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of associated with the adhesion process and biofilm formation.

The chlorogenic acid showed antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets , CYP51, 1 e -B-(1,3)- demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme.

We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti- activity and ability to interact with important drug targets.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Candida spp , chlorogenic acid , flow cytometry and molecular docking
© 2022 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001526
2022-05-16
2024-04-19
Loading full text...

Full text loading...

References

  1. Suleyman G, Alangaden GJ. Nosocomial fungal infections: epidemiology, infection control, and prevention. Infect Dis Clin North Am 2016; 30:1023–1052 [View Article] [PubMed]
     [Google Scholar]
  2. Ha YE, Peck KR, Joo E-J, Kim SW, Jung S-I et al. Impact of first-line antifungal agents on the outcomes and costs of candidemia. Antimicrob Agents Chemother 2012; 56:3950–3956 [View Article] [PubMed]
     [Google Scholar]
  3. Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998; 27:781–788 [View Article] [PubMed]
     [Google Scholar]
  4. Braga PR, Cruz IL, Ortiz I, Barreiros G, Nouér SA et al. Secular trends of candidemia at a Brazilian tertiary care teaching hospital. Braz J Infect Dis 2018; 22:273–277 [View Article] [PubMed]
     [Google Scholar]
  5. Motta AL, Almeida GMD de, Almeida Júnior JN de, Burattini MN, Rossi F. Candidemia epidemiology and susceptibility profile in the largest Brazilian teaching hospital complex. Braz J Infect Dis 2010; 14:441–448 [PubMed]
     [Google Scholar]
  6. Anderson MZ, Saha A, Haseeb A, Bennett RJ. A chromosome 4 trisomy contributes to increased fluconazole resistance in a clinical isolate of Candida albicans. Microbiology (Reading) 2017; 163:856–865 [View Article] [PubMed]
     [Google Scholar]
  7. Pinhati HMS, Casulari LA, Souza ACR, Siqueira RA, Damasceno CMG et al. Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit. BMC Infect Dis 2016; 16:433 [View Article] [PubMed]
     [Google Scholar]
  8. Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide. Clin Microbiol Infect 2019; 25:792–798 [View Article]
     [Google Scholar]
  9. Khan Z, Ahmad S, Al-Sweih N, Mokaddas E, Al-Banwan K et al. Increasing trends of reduced susceptibility to antifungal drugs among clinical Candida glabrata isolates in Kuwait. Microbial Drug Resistance 2020; 26:982–990 [View Article] [PubMed]
     [Google Scholar]
  10. Calderone R, Sun N, Gay-Andrieu F, Groutas W, Weerawarna P et al. Antifungal drug discovery: The process and outcomes. Future Microbiol 2014; 9:791–805 [View Article]
     [Google Scholar]
  11. Liu S, Hou Y, Chen X, Gao Y, Li H et al. Combination of fluconazole with non-antifungal agents: A promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery. Int J Antimicrob Agents 2014; 43:395–402 [View Article] [PubMed]
     [Google Scholar]
  12. Schleinkofer K, Wang T, Wade RC. Molecular docking. Encycl Ref Genomics Proteomics Mol Med 2006; 443:1149–1153
     [Google Scholar]
  13. Roudbarmohammadi S, Roudbary M, Bakhshi B, Katiraee F, Mohammadi R et al. ALS1 and ALS3 gene expression and biofilm formation in Candida albicans isolated from vulvovaginal candidiasis. Adv Biomed Res 2016; 5:105 [View Article] [PubMed]
     [Google Scholar]
  14. Winter MB, Salcedo EC, Lohse MB, Hartooni N, Gulati M et al. Global identification of biofilm-specific proteolysis in Candida albicans. mBio 2016; 7:e01514–16 [View Article] [PubMed]
     [Google Scholar]
  15. Kioshima ES, Shinobu-Mesquita CS, Abadio AKR, Felipe MSS, Svidzinski TIE et al. Selection of potential anti-adhesion drugs by in silico approaches targeted to ALS3 from Candida albicans. Biotechnol Lett 2019; 41:1391–1401 [View Article] [PubMed]
     [Google Scholar]
  16. Sinha K, Rule GS. The structure of thymidylate kinase from Candida albicans reveals a unique structural element. Biochemistry 2017; 56:4360–4370 [View Article] [PubMed]
     [Google Scholar]
  17. Liu D, Meng S, Xiang Z, He N, Yang G. Antimicrobial mechanism of reaction products of Morus notabilis (mulberry) polyphenol oxidases and chlorogenic acid. Phytochemistry 2019; 163:1–10 [View Article] [PubMed]
     [Google Scholar]
  18. Naveed M, Hejazi V, Abbas M, Kamboh AA, Khan GJ et al. Chlorogenic acid (CGA): A pharmacological review and call for further research. Biomed Pharmacother 2018; 97:67–74 [View Article] [PubMed]
     [Google Scholar]
  19. Yamagata K, Izawa Y, Onodera D, Tagami M. Chlorogenic acid regulates apoptosis and stem cell marker-related gene expression in A549 human lung cancer cells. Mol Cell Biochem 2018; 441:9–19 [View Article] [PubMed]
     [Google Scholar]
  20. Gao R, Yang H, Jing S, Liu B, Wei M et al. Protective effect of chlorogenic acid on lipopolysaccharide-induced inflammatory response in dairy mammary epithelial cells. Microb Pathog 2018; 124:178–182 [View Article] [PubMed]
     [Google Scholar]
  21. Xu JG, Hu QP, Liu Y. Antioxidant and DNA-protective activities of chlorogenic acid isomers. J Agric Food Chem 2012; 60:11625–11630 [View Article] [PubMed]
     [Google Scholar]
  22. Liu YJ, Zhou CY, Qiu CH, Lu XM, Wang YT. Chlorogenic acid induced apoptosis and inhibition of proliferation in human acute promyelocytic leukemia HL-60 cells. Mol Med Rep 2013; 8:1106–1110 [View Article] [PubMed]
     [Google Scholar]
  23. Ohnishi M, Morishita H, Iwahashi H, Toda S, Shirataki Y et al. Inhibitory effects of chlorogenic acids on linoleic acid peroxidation and haemolysis. Phytochemistry 1994; 36:579–583 [View Article]
     [Google Scholar]
  24. Sung WS, Lee DG. Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. Pure Appl Chem 2010; 82:219–226 [View Article]
     [Google Scholar]
  25. Yun JE, Lee DG. Role of potassium channels in chlorogenic acid-induced apoptotic volume decrease and cell cycle arrest in Candida albicans. Biochimica et Biophysica Acta (BBA) - General Subjects 2017; 1861:585–592 [View Article] [PubMed]
     [Google Scholar]
  26. Clinical Laboratory Standard Institute-CLSI CLSI document M27-A3. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard—third edition 2008
     [Google Scholar]
  27. Clinical Laboratory Standard Institute-CLSI CLSI document M27-S4. Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement 2012
     [Google Scholar]
  28. da Silva CR, de Andrade Neto JB, Sidrim JJC, Angelo MRF, Magalhães HIF et al. Synergistic effects of amiodarone and fluconazole on Candida tropicalis resistant to fluconazole. Antimicrob Agents Chemother 2013; 57:1691–1700 [View Article] [PubMed]
     [Google Scholar]
  29. Neto JBA, da Silva CR, Neta MAS, Campos RS, Siebra JT et al. Antifungal activity of naphthoquinoidal compounds in vitro against fluconazole-resistant strains of different Candida species: A special emphasis on mechanisms of action on Candida tropicalis. PLoS One 2014; 9:e93698 [View Article] [PubMed]
     [Google Scholar]
  30. Neto JBA, Silva CR, Nascimento F, Sampaio LS, Silva AR et al. Screening of antimicrobial metabolite yeast isolates derived biome ceará against pathogenic bacteria, including MRSA: antibacterial activity and mode of action evaluated by flow cytometry. International Journal of Current Microbiology and Applied Sciences 2015; 4:459–472
     [Google Scholar]
  31. Batista de Andrade Neto J, Alexandre Josino MA, Rocha da Silva C, de Sousa Campos R, Aires do Nascimento FBS et al. A mechanistic approach to the in-vitro resistance modulating effects of fluoxetine against meticillin resistant Staphylococcus aureus strains. Microb Pathog 2019; 127:335–340 [View Article] [PubMed]
     [Google Scholar]
  32. Halgren TA. Merck molecular force field. II. MMFF94 van der waals and electrostatic parameters for intermolecular interactions. J Comput Chem 1996; 17:520–552
     [Google Scholar]
  33. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E et al. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 2012; 4:17 [View Article] [PubMed]
     [Google Scholar]
  34. ChemAxonMarvinSketch version 19.13.0 2019 https://chemaxon.com/products/marvin
  35. Csizmadia P. MarvinSketch and marvinview: molecule applets for the world wide web; 2019 https://chemaxon.com/presentation/marvinsketch-and-marvinview-molecule-applets-for-the-world-wide-web
  36. Huey R, Morris GM, Forli S. Using AutoDock 4 and AutoDock Vina with AutoDockTools: A Tutorial; 2012 https://www.moodle.is.ed.ac.uk/pluginfile.php/87431/mod_resource/content/1/2012_ADTtut.pdf
  37. Trott O, Olson AJ. Software news and update autodock vina: improving the speed and accuracy of docking with a new scoring function efficient optimization, and multithreading. J Comput Chem 2010; 31:455–461
     [Google Scholar]
  38. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM et al. UCSF Chimera — A visualization system for exploratory research and analysis. J Comput Chem 2004; 25:1605–1612 [View Article] [PubMed]
     [Google Scholar]
  39. BIOVIA Discovery StudioDiscovery Studio Modeling Environment, Release San Diego: Dassault Systèmes; 2017 https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio/
  40. DeLano WL. The PyMOL Molecular Graphics System, Version 2.3 Schrödinger LLC; 2019 https://pymol.org/2/
  41. Trincao J, Johnson RE, Escalante CR, Prakash S, Prakash L et al. Structure of the Catalytic Core of S. cerevisiae DNA Polymerase η. Molecular Cell 2001; 8:417–426 [View Article] [PubMed]
     [Google Scholar]
  42. Znosko BM, Kennedy SD, Wille PC, Krugh TR, Turner DH. Structural features and thermodynamics of the J4/5 loop from the Candida albicans and Candida dubliniensis Group I Introns. Biochemistry 2004; 43:15822–15837 [View Article] [PubMed]
     [Google Scholar]
  43. Yu EY, Sun J, Lei M, Lue NF. Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer Arrangement, Dimerization-Assisted DNA Binding, and Substantial Structural Differences between Cdc13 and RPA70. Mol Cell Biol 2012; 32:186–198 [View Article] [PubMed]
     [Google Scholar]
  44. Gleason JE, Galaleldeen A, Peterson RL, Taylor AB, Holloway SP et al. Candida albicans SOD5 represents the prototype of an unprecedented class of Cu-only superoxide dismutases required for pathogen defense. Proc Natl Acad Sci U S A 2014; 111:5866–5871 [View Article] [PubMed]
     [Google Scholar]
  45. Cutfield JF, Sullivan PA, Cutfield SM. Minor structural consequences of alternative CUG codon usage (Ser for Leu) in Candida albicans exoglucanase. Protein Eng 2000; 13:735–738 [View Article] [PubMed]
     [Google Scholar]
  46. van den Berg B, Chembath A, Jefferies D, Basle A, Khalid S et al. Structural basis for Mep2 ammonium transceptor activation by phosphorylation. Nat Commun 2016; 7:11337 [View Article] [PubMed]
     [Google Scholar]
  47. Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ et al. Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. J Biol Chem 2017; 292:6728–6743 [View Article] [PubMed]
     [Google Scholar]
  48. Lange C, Nett JH, Trumpower BL, Hunte C. Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure. EMBO J 2001; 20:6591–6600 [View Article] [PubMed]
     [Google Scholar]
  49. Schägger H, Link TA, Engel WD, von Jagow G. Isolation of the eleven protein subunits of the bc1 complex from beef heart; 1986224–237
  50. Yan J, Zhang G, Pan J, Wang Y. α-Glucosidase inhibition by luteolin: Kinetics, interaction and molecular docking. Int J Biol Macromol 2014; 64:213–223 [View Article] [PubMed]
     [Google Scholar]
  51. Marinho EM, Batista de Andrade Neto J, Silva J, Rocha da Silva C, Cavalcanti BC et al. Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease. Microb Pathog 2020; 148:104365 [View Article] [PubMed]
     [Google Scholar]
  52. Yusuf D, Davis AM, Kleywegt GJ, Schmitt S. An alternative method for the evaluation of docking performance: RSR vs RMSD. J Chem Inf Model 2008; 48:1411–1422 [View Article] [PubMed]
     [Google Scholar]
  53. Shityakov S, Förster C. In silico predictive model to determine vector-mediated transport properties for the blood-brain barrier choline transporter. Adv Appl Bioinform Chem 2014; 7:23–36 [View Article] [PubMed]
     [Google Scholar]
  54. Kadela-Tomanek M, Jastrzębska M, Marciniec K, Chrobak E, Bębenek E et al. Lipophilicity, Pharmacokinetic Properties, and Molecular Docking Study on SARS-CoV-2 Target for Betulin Triazole Derivatives with Attached 1,4-Quinone. Pharmaceutics 2021; 13:781 [View Article] [PubMed]
     [Google Scholar]
  55. Imberty A, Hardman KD, Carver JP, Pérez S. Molecular modelling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology 1991; 1:631–642 [View Article] [PubMed]
     [Google Scholar]
  56. Borelli C, Ruge E, Lee JH, Schaller M, Vogelsang A et al. X-ray structures of Sap1 and Sap5: Structural comparison of the secreted aspartic proteinases from Candida albicans. Proteins 2008; 72:1308–1319 [View Article] [PubMed]
     [Google Scholar]
  57. Lin J, Oh S-H, Jones R, Garnett JA, Salgado PS et al. The peptide-binding cavity is essential for ALS3-mediated adhesion of Candida albicans to human cells. J Biol Chem 2014; 289:18401–18412 [View Article] [PubMed]
     [Google Scholar]
  58. Guerra TM. Estudos de Docking Molecular de Derivados da Tiazolidina Como Potenciais Inibidores da Enzima Cruzaína de Trypanosoma cruzi Universidade Federal Rural de Pernambuco/ Unidade Acadêmica de Serra Talhada-PE; 2019
     [Google Scholar]
  59. Melo Lucio FN, Da Silva JE, Marinho EM, Da Silva Mendes FR, Marinho MM et al. Methylcytisine alcaloid potentially active against dengue virus: a molecular docking study and electronic structural characterization. Int J Res Granthaalayah 2020; 8:221–236 [View Article]
     [Google Scholar]
  60. DASSAULT SYSTÈMES BIOVIADiscovery Studio Visualizer, Versão 16.1.0 https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio/visualization/
  61. Puupponen-Pimiä R, Nohynek L, Meier C, Kähkönen M, Heinonen M et al. Antimicrobial properties of phenolic compounds from berries. J Appl Microbiol 2001; 90:494–507 [View Article] [PubMed]
     [Google Scholar]
  62. Li G, Qiao M, Guo Y, Wang X, Xu Y et al. Effect of subinhibitory concentrations of chlorogenic acid on reducing the virulence factor production by Staphylococcus aureus. Foodborne Pathog Dis 2014; 11:677–683 [View Article] [PubMed]
     [Google Scholar]
  63. Li G, Wang X, Xu Y, Zhang B, Xia X. Antimicrobial effect and mode of action of chlorogenic acid on Staphylococcus aureus. Eur Food Res Technol 2013; 238:589–596 [View Article]
     [Google Scholar]
  64. Fu L, Lu WQ, Zhou XM. Phenolic compounds and in vitro antibacterial and antioxidant activities of three tropic fruits: persimmon, Guava, and Sweetsop. Biomed Res Int 2016; 2016:4287461 [View Article] [PubMed]
     [Google Scholar]
  65. Khalil MI. Molecular docking and analysis of MEP2 protein in Candida albicans membrane. EurAsian J Biosci 2020; 14:4373–4376
     [Google Scholar]
  66. Hwang I-S, Lee J, Jin H-G, Woo E-R, Lee DG. Amentoflavone stimulates mitochondrial dysfunction and induces apoptotic cell death in Candida albicans. Mycopathologia 2012; 173:207–218 [View Article] [PubMed]
     [Google Scholar]
  67. Hwang JH, Hwang IS, Liu QH, Woo ER, Lee DG. (+)-Medioresinol leads to intracellular ROS accumulation and mitochondria-mediated apoptotic cell death in Candida albicans. Biochimie 2012; 94:1784–1793 [View Article] [PubMed]
     [Google Scholar]
  68. da Silva AR, de Andrade Neto JB, da Silva CR, Campos R de S, Costa Silva RA et al. Berberine antifungal activity in fluconazole-resistant pathogenic yeasts: action mechanism evaluated by flow cytometry and biofilm growth inhibition in Candida spp. Antimicrob Agents Chemother 2016; 60:3551–3557 [View Article] [PubMed]
     [Google Scholar]
  69. Lam P-L, Wong RS-M, Lam K-H, Hung L-K, Wong M-M et al. The role of reactive oxygen species in the biological activity of antimicrobial agents: An updated mini review. Chem Biol Interact 2020; 320:109023 [View Article] [PubMed]
     [Google Scholar]
  70. Hubbard RE, Kamran Haider M. Hydrogen bonds in proteins: role and strength. Encycl Life Sci 2010 [View Article]
     [Google Scholar]
  71. Frohner IE, Bourgeois C, Yatsyk K, Majer O, Kuchler K. Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol Microbiol 2009; 71:240–252 [View Article] [PubMed]
     [Google Scholar]
  72. Miramón P, Dunker C, Windecker H, Bohovych IM, Brown AJP et al. Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress. PLoS ONE 2012; 7:e52850 [View Article]
     [Google Scholar]
  73. Choi H, Lee DG. Lycopene induces apoptosis in Candida albicans through reactive oxygen species production and mitochondrial dysfunction. Biochimie 2015; 115:108–115 [View Article] [PubMed]
     [Google Scholar]
  74. Liao Z, Zhu Z, Li L, Wang L, Wang H et al. Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin. Emerg Microbes Infect 2019; 8:1243–1253 [View Article] [PubMed]
     [Google Scholar]
  75. Acharya N, Manohar K, Nayak S, Chatterjee A, Dalei A. DNA Polymerase: A putative drug target against candidiasis. Front Life Sci 2016; 12–22:
     [Google Scholar]
  76. Mason M, Wanat JJ, Harper S, Schultz DC, Speicher DW et al. Cdc13 OB2 dimerization required for productive Stn1 binding and efficient telomere maintenance. Structure 2013; 21:109–120 [View Article] [PubMed]
     [Google Scholar]
  77. Lastauskienė E, Zinkevičienė A, Girkontaitė I, Kaunietis A, Kvedarienė V. Formic acid and acetic acid induce a programmed cell death in pathogenic Candida species. Curr Microbiol 2014; 69:303–310 [View Article] [PubMed]
     [Google Scholar]
  78. Hoyer LL, Green CB, Oh SH, Zhao X. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family - A sticky pursuit. Med Mycol 2008; 46:1–15 [View Article] [PubMed]
     [Google Scholar]
  79. Silva DR, Sardi J de CO, Freires IA, Silva ACB, Rosalen PL. In silico approaches for screening molecular targets in Candida albicans: A proteomic insight into drug discovery and development. Eur J Pharmacol 2019; 842:64–69 [View Article] [PubMed]
     [Google Scholar]
  80. Freire F, de Barros PP, da Silva Ávila D, Brito GNB, Junqueira JC et al. Evaluation of gene expression SAP5, LIP9, and PLB2 of Candida albicans biofilms after photodynamic inactivation. Lasers Med Sci 2015; 30:1511–1518 [View Article] [PubMed]
     [Google Scholar]
  81. Magalhães L de, Reis ACC, Nakao IA, Péret VAC, Reis R et al. Glucosyl‐1,2,3‐triazoles derived from eugenol and analogues: synthesis, anti‐Candida activity and molecular modeling studies in CYP‐51. Chem Biol Drug Des 2021; 98:903–913 [View Article]
     [Google Scholar]
  82. Vincent BM, Langlois J-B, Srinivas R, Lancaster AK, Scherz- R et al. A fungal-selective cytochrome bc1 inhibitor impairs virulence and prevents the evolution of drug resistance. Cell Chem Biol 2016; 23:978–991 [View Article] [PubMed]
     [Google Scholar]
  83. Chambers RS, Broughton MJ, Cannon RD, Carne A, Emerson GW et al. An exo-B-(1,3)-glucanase of Candida albicans: purification of the enzyme and molecular cloning of the gene. J Gen Microbiol 1993; 139:325–334 [View Article] [PubMed]
     [Google Scholar]
  84. Gonçalves B, Moeenfard M, Rocha F, Alves A, Estevinho BN et al. Microencapsulation of a natural antioxidant from coffee—chlorogenic acid (3-Caffeoylquinic Acid). Food Bioprocess Technol 2017; 10:1521–1530 [View Article]
     [Google Scholar]
  85. Kitagawa S, Yoshii K, Morita S, Teraoka R. Efficient topical delivery of chlorogenic acid by an oil-in-water microemulsion to protect skin against UV-induced damage. Chem Pharm Bull 2011; 59:793–796 [View Article]
     [Google Scholar]
  86. Yutani R, Kikuchi T, Teraoka R, Kitagawa S. Efficient delivery and distribution in skin of chlorogenic acid and resveratrol induced by microemulsion using sucrose laurate. Chem Pharm Bull (Tokyo) 2014; 62:274–280 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001526
Loading
Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action
J. Med. Microbiol. 71, 001526 (2022); https://doi.org/10.1099/jmm.0.001526
/content/journal/jmm/10.1099/jmm.0.001526
/content/journal/jmm/10.1099/jmm.0.001526
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error