{"title":"生姜酮对白色念珠菌生长和生物膜生成的抑制作用。","authors":"Sayali Chougule , Sargun Basrani , Tanjila Gavandi , Shivani Patil , Shivanand Yankanchi , Ashwini Jadhav , Sankunny Mohan Karuppayil","doi":"10.1016/j.mycmed.2024.101527","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The increasing resistance of <em>Candida albicans</em> biofilms underscores the urgent need for effective antifungals. This study evaluated the efficacy of zingerone and elucidated its mode of action against <em>C. albicans</em> ATCC 90028 and clinical isolate C1.</div></div><div><h3>Experimental Procedure</h3><div>Minimum inhibitory concentrations (MICs) of zingerone were determined using CLSI methods against planktonic cells, biofilm formation, and yeast-to-hyphal transition. The mode of action was investigated through fluorescent microscopy, ergosterol assays, cell cycle analysis, and RT-PCR for gene expression.</div></div><div><h3>Key Results</h3><div>Zingerone inhibited planktonic growth and biofilm formation at in <em>C. albicans</em> ATCC 90028 and clinical isolate C1 at 2 mg/mL 4 mg/mL and 1 mg/mL and 2 mg/mL respectively. Treatment with the MIC concentration caused significant cell cycle arrest at the G0/G1 phase, halting proliferation in both the strains. Propidium iodide Staining revealed compromised membrane integrity in both the strains. Also, acridine orange and ethidium bromide dual staining showed increased dead cell proportions in <em>C. albicans</em> ATCC 90028. RT-PCR studies showed downregulation of <em>BCY1, PDE2, EFG1</em>, and upregulation of negative regulators <em>NRG1, TUP1</em> disrupting growth and virulence pathways. Zingerone induced elevated reactive oxygen species (ROS) levels, triggering apoptosis, evidenced by DNA fragmentation and upregulation of apoptotic markers. It also inhibited ergosterol synthesis in a concentration-dependent manner, crucial for membrane integrity. Importantly, zingerone exhibited minimal hemolytic activity. In an <em>in vivo</em> silkworm model, zingerone demonstrated significant antifungal efficacy, protecting silkworms from infection. It also modulated stress response genes, highlighting its multifaceted action.</div></div><div><h3>Conclusions</h3><div><em>In vitro</em> and <em>in vivo</em> findings confirm the potent antifungal efficacy of zingerone against <em>C. albicans</em> ATCC 90028 and clinical isolate C1, suggesting its promising potential as a therapeutic agent that warrants further exploration.</div></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"35 1","pages":"Article 101527"},"PeriodicalIF":2.2000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zingerone effect against Candida albicans growth and biofilm production\",\"authors\":\"Sayali Chougule , Sargun Basrani , Tanjila Gavandi , Shivani Patil , Shivanand Yankanchi , Ashwini Jadhav , Sankunny Mohan Karuppayil\",\"doi\":\"10.1016/j.mycmed.2024.101527\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>The increasing resistance of <em>Candida albicans</em> biofilms underscores the urgent need for effective antifungals. This study evaluated the efficacy of zingerone and elucidated its mode of action against <em>C. albicans</em> ATCC 90028 and clinical isolate C1.</div></div><div><h3>Experimental Procedure</h3><div>Minimum inhibitory concentrations (MICs) of zingerone were determined using CLSI methods against planktonic cells, biofilm formation, and yeast-to-hyphal transition. The mode of action was investigated through fluorescent microscopy, ergosterol assays, cell cycle analysis, and RT-PCR for gene expression.</div></div><div><h3>Key Results</h3><div>Zingerone inhibited planktonic growth and biofilm formation at in <em>C. albicans</em> ATCC 90028 and clinical isolate C1 at 2 mg/mL 4 mg/mL and 1 mg/mL and 2 mg/mL respectively. Treatment with the MIC concentration caused significant cell cycle arrest at the G0/G1 phase, halting proliferation in both the strains. Propidium iodide Staining revealed compromised membrane integrity in both the strains. Also, acridine orange and ethidium bromide dual staining showed increased dead cell proportions in <em>C. albicans</em> ATCC 90028. RT-PCR studies showed downregulation of <em>BCY1, PDE2, EFG1</em>, and upregulation of negative regulators <em>NRG1, TUP1</em> disrupting growth and virulence pathways. Zingerone induced elevated reactive oxygen species (ROS) levels, triggering apoptosis, evidenced by DNA fragmentation and upregulation of apoptotic markers. It also inhibited ergosterol synthesis in a concentration-dependent manner, crucial for membrane integrity. Importantly, zingerone exhibited minimal hemolytic activity. In an <em>in vivo</em> silkworm model, zingerone demonstrated significant antifungal efficacy, protecting silkworms from infection. It also modulated stress response genes, highlighting its multifaceted action.</div></div><div><h3>Conclusions</h3><div><em>In vitro</em> and <em>in vivo</em> findings confirm the potent antifungal efficacy of zingerone against <em>C. albicans</em> ATCC 90028 and clinical isolate C1, suggesting its promising potential as a therapeutic agent that warrants further exploration.</div></div>\",\"PeriodicalId\":14824,\"journal\":{\"name\":\"Journal de mycologie medicale\",\"volume\":\"35 1\",\"pages\":\"Article 101527\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-12-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal de mycologie medicale\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1156523324000684\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MYCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal de mycologie medicale","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1156523324000684","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MYCOLOGY","Score":null,"Total":0}
Zingerone effect against Candida albicans growth and biofilm production
Background
The increasing resistance of Candida albicans biofilms underscores the urgent need for effective antifungals. This study evaluated the efficacy of zingerone and elucidated its mode of action against C. albicans ATCC 90028 and clinical isolate C1.
Experimental Procedure
Minimum inhibitory concentrations (MICs) of zingerone were determined using CLSI methods against planktonic cells, biofilm formation, and yeast-to-hyphal transition. The mode of action was investigated through fluorescent microscopy, ergosterol assays, cell cycle analysis, and RT-PCR for gene expression.
Key Results
Zingerone inhibited planktonic growth and biofilm formation at in C. albicans ATCC 90028 and clinical isolate C1 at 2 mg/mL 4 mg/mL and 1 mg/mL and 2 mg/mL respectively. Treatment with the MIC concentration caused significant cell cycle arrest at the G0/G1 phase, halting proliferation in both the strains. Propidium iodide Staining revealed compromised membrane integrity in both the strains. Also, acridine orange and ethidium bromide dual staining showed increased dead cell proportions in C. albicans ATCC 90028. RT-PCR studies showed downregulation of BCY1, PDE2, EFG1, and upregulation of negative regulators NRG1, TUP1 disrupting growth and virulence pathways. Zingerone induced elevated reactive oxygen species (ROS) levels, triggering apoptosis, evidenced by DNA fragmentation and upregulation of apoptotic markers. It also inhibited ergosterol synthesis in a concentration-dependent manner, crucial for membrane integrity. Importantly, zingerone exhibited minimal hemolytic activity. In an in vivo silkworm model, zingerone demonstrated significant antifungal efficacy, protecting silkworms from infection. It also modulated stress response genes, highlighting its multifaceted action.
Conclusions
In vitro and in vivo findings confirm the potent antifungal efficacy of zingerone against C. albicans ATCC 90028 and clinical isolate C1, suggesting its promising potential as a therapeutic agent that warrants further exploration.
期刊介绍:
The Journal de Mycologie Medicale / Journal of Medical Mycology (JMM) publishes in English works dealing with human and animal mycology. The subjects treated are focused in particular on clinical, diagnostic, epidemiological, immunological, medical, pathological, preventive or therapeutic aspects of mycoses. Also covered are basic aspects linked primarily with morphology (electronic and photonic microscopy), physiology, biochemistry, cellular and molecular biology, immunochemistry, genetics, taxonomy or phylogeny of pathogenic or opportunistic fungi and actinomycetes in humans or animals. Studies of natural products showing inhibitory activity against pathogenic fungi cannot be considered without chemical characterization and identification of the compounds responsible for the inhibitory activity.
JMM publishes (guest) editorials, original articles, reviews (and minireviews), case reports, technical notes, letters to the editor and information. Only clinical cases with real originality (new species, new clinical present action, new geographical localization, etc.), and fully documented (identification methods, results, etc.), will be considered.
Under no circumstances does the journal guarantee publication before the editorial board makes its final decision.
The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.