scholarly journals Antifungal activity of eugenol on Cryptococcus neoformans biological activity and Cxt1p gene expression

Author(s):  
Parviz Hassanpour ◽  
Masoomeh Shams-Ghahfarokhi ◽  
Mehdi Razzaghi-Abyaneh

Background and Purpose: The present study was targeted toward investigating the effects of eugenol on Cryptococcus neoformans biological activity and Cxt1p gene expression. Materials and Methods: For the purpose of the study, the growth, urease, synergism activity, and disk diffusion of C. neoformans were assessed in eugenol-treated culture. The minimum inhibitory concentration (MIC) was determined by the Clinical and Laboratory Standards Institute M27-A3 method at a concentration range of 0.062-2 mg/mL. Subsequently, the expression of Cxt1p genes was studied at the MIC50 concentration of eugenol using real-time polymerase chain reaction. Results: The obtained results showed that eugenol at the concentrations of 125 and 500 μg/mL resulted in 50% and 100% growth inhibition in C. neoformans, respectively. In terms of urease activity, the results showed that the addition of MIC50 of eugenol and fluconazole to urea medium reduced urease activity in C. neoformans. In the culture treated with eugenol, the inhibition zone of antifungal drugs, namely amphotericin B, itraconazole, and fluconazole, was increased to 36±0.002, 22±0.001, and 12±0.002 mm, respectively. The expression levels of Cxt1p in the eugenol-treated, fluconazole-treated, and non-treated samples were estimated at 46%, 58%, and 100%, respectively. Conclusion: The findings of the current study revealed that eugenol could cause C. neoformans growth inhibition and reduce Cxt1p expression in this species. As the results indicated, the susceptibility of C. neoformans to fluconazole was increased when combined with eugenol.

Author(s):  
Seyed Afzal Musavinasab-Mobarakeh ◽  
Masoomeh Shams-Ghahfarokhi ◽  
Mehdi Razzaghi-Abyaneh

Background and Purpose: This study aimed to investigate the effects of Allium cepa ethanolic extract (EAC) on Cryptococcus neoformans biological activities and LAC1 gene expression. Materials and Methods: The minimum inhibitory concentration (MIC) of EAC was determined based on the Clinical and Laboratory Standards Institute M27-A4 method at a concentration range of 125- 4000 µg/ml. The EAC synergism activity was determined in combination with fluconazole (FCZ) as an antifungal azole. Laccase activity, melanin production, and cell membrane ergosterol content of C. neoformans were assessed at the 0.5× MIC concentration of EAC (1000 μg/ml) and FCZ (64μg/ml) by approved methods. The expression of the LAC1 gene was studied in the fungus exposed to 0.5× MIC concentration of EAC and FCZ using the real-time polymerase chain reaction. Results: Based on obtained results, MIC of EAC and FCZ were 2000 and 128 μg/ml,respectively. A combinatory effect was reported for FCZ and EAC by a fractional inhibitory concentration index of 0.25. The cell membrane ergosterol content was inhibited in EAC- and FCZ-treated C. neoformans by 58.25% and 49.85%, respectively.The laccase activity and melanin production were reduced in EAC-treated C. neoformans by 45.37% and 51.57%, and in FCZ-treated fungus by 54.64% and 53.68%, respectively.The expression of fungal LAC1 at messenger RNA (mRNA) level was measured 0.46 and 0.58 folds and significantly decreased in both EAC- and FCZ-treated C. neoformans at the 0.5×MIC concentration, respectively (p <0.05). Conclusion: The findings revealed that EAC contains inhibitory compounds which interact with biological activities in C. neoformans and thereby, it could be considered as a potential source for the development of novel antifungal drugs.


2021 ◽  
Vol 36 (1) ◽  
pp. 14-18
Author(s):  
Forman Erwin Siagian ◽  
Dena Carolina Sabono ◽  
Muhammad Alfarabi

Abstrak Candida sp. dan Cryptococcus sp. merupakan jamur oportunistik yang dapat menyebabkan penyakit pada manusia dan dapat berakibat fatal jika tidak ditangani dengan cepat dan tepat. Saat ini terdapat permasalahan yaitu resistensi antijamur dan jenis terapi terhadap jamur yang terbatas. Terdapatnya bahan alam yang melimpah di Indonesia menjadi suatu potensi untuk mengembangkan obat anti jamur baru yang memiliki efektivitas tinggi, efek samping yang minimal, dan murah. Salah satu bahan alam yang belum tereksplorasi untuk antijamur adalah biji pepaya varietas bangkok. Biji pepaya selama ini lebih banyak menjadi limbah organik. Oleh karena hal tersebut, tujuan dari penelitian ini adalah untuk menguji aktivitas antijamur dari ekstrak biji pepaya bangkok (Carica papaya L.). Jamur yang digunakan pada penelitian ini adalah Candida albicans dan Cryptococcus neoformans. Metode yang digunakan adalah perhitungan zona hambat pada sumur di cawan petri. Hasil penelitian menunjukkan bahwa tidak terdapat zona hambat pada media yang terdapat C. albicans dan C. neoformans.  Dapat disimpulkan, ekstrak biji papaya tidak memiliki aktivitas antijamur terhadap kedua jamur tersebut. Kata kunci: Pepaya bangkok, Antijamur, Bahan alam Abstract Candida sp. and Cryptococcus sp. are opportunistic fungi that can be fatal disease in humans if not treated properly. However, resistance of antifungal drugs have been emerged, therefore limit their benefit for therapy. Many natural products in Indonesia have potential to be established for new antifungal drugs that have high effectiveness, minimal side effects, and inexpensive. Papaya bangkok seed has not been explored for its antifungal activity. This seed become more organic waste. The aim of this study was to test antifungal activity of various papaya bangkok seed extract concentrations. We measured the inhibiton zone of papaya extract to Candida albicans and Cryptococcus neoformans. Result showed no inhibition zone for each seed extract concentrations. Papaya bangkok seed extract has not antifungal activity. Keywords: Papaya bangkok, antifungal, natural product


1999 ◽  
Vol 20 (2) ◽  
pp. 230 ◽  
Author(s):  
Marianne Jorgensen ◽  
Maja Bévort ◽  
Thuri S. Kledal ◽  
Brian V. Hansen ◽  
Marlene Dalgaard ◽  
...  

2019 ◽  
Vol 26 (39) ◽  
pp. 6976-6990 ◽  
Author(s):  
Ana María González-Paramás ◽  
Begoña Ayuda-Durán ◽  
Sofía Martínez ◽  
Susana González-Manzano ◽  
Celestino Santos-Buelga

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.


2019 ◽  
Vol 20 (11) ◽  
pp. 918-923 ◽  
Author(s):  
Yazun Jarrar ◽  
Qais Jarrar ◽  
Mohammad Abu-Shalhoob ◽  
Abdulqader abed ◽  
Esra'a Sha'ban

Background: Mouse Udp-glucuronosyl Transferase (UGT) 2b1 is equivalent to the human UGT2B7 enzyme, which is a phase II drug-metabolising enzyme and plays a major role in the metabolism of xenobiotic and endogenous compounds. This study aimed to find the relative expression of the mouse ugt2b1 gene in the liver, kidney, and heart organs and the influence of Nonsteroidal Anti-inflammatory Drug (NSAID) administration. Methods: Thirty-five Blab/c mice were divided into 5 groups and treated with different commonly-used NSAIDs; diclofenac, ibuprofen, meloxicam, and mefenamic acid for 14 days. The livers, kidneys, and hearts were isolated, while the expression of ugt2b1 gene was analysed with a quantitative real-time polymerase chain reaction technique. Results: It was found that the ugt2b1 gene is highly expressed in the liver, and then in the heart and the kidneys. NSAIDs significantly upregulated (ANOVA, p < 0.05) the expression of ugt2b1 in the heart, while they downregulated its expression (ANOVA, p < 0.05) in the liver and kidneys. The level of NSAIDs’ effect on ugt2b1 gene expression was strongly correlated (Spearman’s Rho correlation, p < 0.05) with NSAID’s lipophilicity in the liver and its elimination half-life in the heart. Conclusion: This study concluded that the mouse ugt2b1 gene was mainly expressed in the liver, as 14-day administration of different NSAIDs caused alterations in the expression of this gene, which may influence the metabolism of xenobiotic and endogenous compounds.


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 78
Author(s):  
Melissa Bello-Perez ◽  
Mikolaj Adamek ◽  
Julio Coll ◽  
Antonio Figueras ◽  
Beatriz Novoa ◽  
...  

Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.


Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1071
Author(s):  
Tae-Won Jang ◽  
Jae-Ho Park

One of the Korean endemic plants, Abeliophyllum distichum Nakai (Oleaceae), contains acteoside, which is a glycoside exhibiting neuroprotective, anti-inflammation effects and antibacterial capacities. We conducted an investigation on the effects of the callus of A. distichum (cultivar Okhwang 1, CAO) on pro-inflammatory mediators released following nuclear factor-кB (NF-кB), phosphatidylinositol 3-kinase/Akt (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signal activation in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Immunoblotting was employed to find out the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and activation of MAPK molecules, NF-κB and Akt. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. High-performance liquid chromatography revealed that CAO was rich in acteoside and isoacteoside. As a result, CAO inhibited the generation of NO, cytokines, COX-2, and iNOS expression. Further, translocation to the nuclear of NF-κB p65 and degradation of the inhibitor of NF-кB (IкB) were alleviated by suppressing phosphorylation. Additionally, CAO significantly impacted MAPK pathway activation by potentially reducing phosphorylation of MAPKs. These results indicate that the anti-inflammatory effect of CAO is mediated via the inhibition of MAPK, PI3K/Akt, and NF-κB signaling pathways, probably via glycosides, phenolics, and flavonoids bioactivity derived from plants. CAO can serve as a potential anti-inflammatory agent, which alleviates inflammation factors and act through specific cell signaling pathways.


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