Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis DOI Creative Commons
Cong Fan, Lingwen Gu, Jing Lin

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

To investigate the anti-inflammatory and antifungal effects of plumbagin (PL) in Aspergillus fumigatus ( A. ) keratitis, minimum inhibitory concentration (MIC), time-killing curve, spore adhesion, crystal violet staining, calcium fluoride white Propidium Iodide (PI) staining were employed to assess activity PL vitro against . The cytotoxicity was assessed using Cell Counting Kit-8 (CCK8). impact on expression HMGB1, LOX-1, TNF-α, IL-1β, IL-6, IL-10 ROS keratitis investigated RT-PCR, ELISA, Western blot, Reactive oxygen species (ROS) assay. therapeutic efficacy through clinical scoring, plate counting, Immunofluorescence Hematoxylin-Eosin (HE) staining. Finally, we found that inhibited growth, biofilm formation disrupted integrity its cell membrane wall. decreased IL-1β levels while increasing fungi-infected mice corneas peritoneal macrophages. Additionally, significantly attenuated HMGB1/LOX-1 pathway reversing promoting effect Boxb (an HMGB1 agonist) HMGB1/LOX-1. Moreover, level ROS. In vivo , scores, neutrophil recruitment, fungal burden all reduced infected treated with PL. summary, inflammatory process can be by regulation HMGB-1/LOX-1 pathway. Simultaneously, exert limiting adhesion formation, as well causing destruction membranes walls.

Language: Английский

Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches DOI
Juan Xiong, Hui Lu, Yuanying Jiang

et al.

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.

Language: Английский

Citations

2
Marine-Derived Metabolites Act as Promising Antifungal Agents DOI Creative Commons

Sijin Hang,

Hui Lu, Yuanying Jiang

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(4), P. 180 - 180

Published: April 17, 2024

The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, echinocandins, face increasing resistance from pathogenic fungi. Therefore, there a pressing need for development novel drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures pharmacological activities. While numerous compounds exhibiting promising activity have been identified, comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we compiled summary derived marine organisms, highlighting diverse action targeting various cellular components, including cell wall, membrane, mitochondria, chromosomes, drug efflux pumps, several biological processes, vesicular trafficking growth hyphae biofilms. This helpful subsequent drugs due its organisms.

Language: Английский

Citations

6
Geldanamycin confers fungicidal properties to azole by triggering the activation of succinate dehydrogenase DOI Creative Commons
Juan Xiong, Li Wang,

Yanru Feng

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 348, P. 122699 - 122699

Published: May 6, 2024

Azoles have been widely employed for the treatment of invasive fungal diseases; however, their efficacy is diminished as pathogenic fungi tolerate them due to fungistatic properties. Geldanamycin (GdA) can render azoles fungicidal by inhibiting ATPase and molecular chaperone activities heat shock protein 90 (Hsp90). Nonetheless, clinical applicability GdA restricted its cytotoxic ansamycin scaffold structure, induction cytoprotective responses, conservative nature Hsp90. Hence, it imperative elucidate mechanism action confer properties mitigate toxic adverse effects associated with GdA. Through various experimental methods, including construction gene-deleted Candida albicans mutants, in vitro drug sensitivity experiments, Western blot analysis, reactive oxygen species (ROS) assays, succinate dehydrogenase activity we identified Hsp90 client proteins tolerance C. azoles. It was observed that effectively hindered entry into mitochondria, resulting alleviation inhibitory effect on dehydrogenase. Consequently, activation led an increased production ROS. within thereby facilitating antifungal against albicans. This research presents a novel approach conferring azoles, which involves specifically disrupting interaction between rather than employing non-specific inhibition

Language: Английский

Citations

6
Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species DOI Creative Commons
Wanqian Li,

Yanru Feng,

Zhe Feng

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 667 - 667

Published: May 29, 2024

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, fungistatic nature FLC renders pathogenic fungi capable developing tolerance towards it. Consequently, converting into a fungicidal agent using adjuvants assumes significance to circumvent resistance perpetuation infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as promising adjuvant enhancing activity from comprehensive library 2372 FDA-approved drugs. PIT could render even at concentrations low 1 μM. The median lethal dose (LD50) was determined be 103.6 mg/kg. We have discovered that achieves its synergistic effect by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, disrupting Golgi function. Candida albicans strain demonstrated notable infect mice found effectively augmented antifungal efficacy against IFIs. an illustrative example how drugs can eliminate FLC.

Language: Английский

Citations

4
The Role of Oxidative Stress in the Antifungal Activity of Two Mollusk Fractions on Resistant Fungal Strains DOI Open Access
Lyudmila Velkova,

Radoslav Abrashev,

Jeny Miteva‐Staleva

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 985 - 985

Published: Jan. 24, 2025

Fungal infections are a significant global public health challenge because of their widespread occurrence, morbidity, and profound social economic consequences. Antifungal resistance is also an increasing concern, posing substantial risk to health. There growing interest in searching for new antifungal drugs isolated from natural sources. This study aimed evaluate the activity novel mollusk fractions against fungal strains resistant nystatin amphotericin B. In addition, role oxidative stress mechanism damage was determined. The mucus garden snail Cornu aspersum (MCa/1-20) hemolymph fraction marine Rapana venosa (HLRv/3-100) were obtained characterized via 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) mass spectrometric -analyses. results demonstrate that spores biomass both have fungicidal effect Penicillium griseofulvum, Aspergillus niger. Compared control group, release intracellular proteins reducing sugars significantly increased treated groups. data showed levels biomarkers (lipid peroxidation oxidatively damaged proteins) downregulated antioxidant enzyme defense, corresponding activity. To our knowledge, this first evaluating as factor fractions’

Language: Английский

Citations

0
Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans DOI
Hao Wu, Zhe Ji, Xin Huang

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(8), P. 3059 - 3070

Published: July 12, 2024

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs constrained. Emerging evidence indicates that enolase holds promise potential target protein combating IFDs; however, there is currently deficiency in medications specifically targeting enolase. This study establishes isobavachalcone (IBC) exhibits noteworthy efficacy both vitro vivo. Moreover, our has demonstrated IBC effectively targets Eno1

Language: Английский

Citations

3
Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis DOI Creative Commons
Cong Fan, Lingwen Gu, Jing Lin

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

To investigate the anti-inflammatory and antifungal effects of plumbagin (PL) in Aspergillus fumigatus ( A. ) keratitis, minimum inhibitory concentration (MIC), time-killing curve, spore adhesion, crystal violet staining, calcium fluoride white Propidium Iodide (PI) staining were employed to assess activity PL vitro against . The cytotoxicity was assessed using Cell Counting Kit-8 (CCK8). impact on expression HMGB1, LOX-1, TNF-α, IL-1β, IL-6, IL-10 ROS keratitis investigated RT-PCR, ELISA, Western blot, Reactive oxygen species (ROS) assay. therapeutic efficacy through clinical scoring, plate counting, Immunofluorescence Hematoxylin-Eosin (HE) staining. Finally, we found that inhibited growth, biofilm formation disrupted integrity its cell membrane wall. decreased IL-1β levels while increasing fungi-infected mice corneas peritoneal macrophages. Additionally, significantly attenuated HMGB1/LOX-1 pathway reversing promoting effect Boxb (an HMGB1 agonist) HMGB1/LOX-1. Moreover, level ROS. In vivo , scores, neutrophil recruitment, fungal burden all reduced infected treated with PL. summary, inflammatory process can be by regulation HMGB-1/LOX-1 pathway. Simultaneously, exert limiting adhesion formation, as well causing destruction membranes walls.

Language: Английский

Citations

2