In Vitro and In Vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms.
Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 μM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use.
Herman Ostrow School of Dentistry, Division of Periodontology Diagnostic Sciences, Dental Hygiene and Biomedical Sciences, University of Southern California, Los Angeles, CA, United States of America.
Dalia
D
Seleem
School of Dentistry, Faculty of Medicine, Universidad Austral de Chile, Campus Isla Teja, Valdivia, Chile.
Bruna
B
Benso
Herman Ostrow School of Dentistry, Division of Periodontology Diagnostic Sciences, Dental Hygiene and Biomedical Sciences, University of Southern California, Los Angeles, CA, United States of America.
Juliana
J
Noguti
Herman Ostrow School of Dentistry, Division of Periodontology Diagnostic Sciences, Dental Hygiene and Biomedical Sciences, University of Southern California, Los Angeles, CA, United States of America.
Vanessa
V
Pardi
Herman Ostrow School of Dentistry, Division of Periodontology Diagnostic Sciences, Dental Hygiene and Biomedical Sciences, University of Southern California, Los Angeles, CA, United States of America.
Ramiro Mendonça
RM
Murata
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D002180:Candidiasis, Oral / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D007378:Interleukins / Q000032:analysis; D051379:Mice; D009055:Mouth / Q000382:microbiology* / Q000473:pathology
D000935:Antifungal Agents; D047188:Chalcones; D007378:Interleukins; C070840:licochalcone A