-
International Journal of Medicinal... 2017Ergosterol peroxide (EP; 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol) is a C28-sterol and a component of many medicinal mushrooms. Since its discovery nearly a century... (Review)
Review
Ergosterol peroxide (EP; 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol) is a C28-sterol and a component of many medicinal mushrooms. Since its discovery nearly a century ago, many sources and biological effects of this compound have been described. Effects range from antimicrobial to cytotoxic to immunosuppressive and other activities. This review covers biological investigations of EP, its activities, and possible mechanisms of action. EP is a promising candidate for drug development and contributes to the health-promoting effects of medicinal mushrooms.
Topics: Agaricales; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Ergosterol; Immunologic Factors
PubMed: 28436318
DOI: 10.1615/IntJMedMushrooms.v19.i2.10 -
Molecular Plant Pathology Sep 2014Fungal pathogens continue to pose a significant threat to crop production and food supply. The early stages of plant-fungus interactions are mostly mediated by... (Review)
Review
Fungal pathogens continue to pose a significant threat to crop production and food supply. The early stages of plant-fungus interactions are mostly mediated by microbe-associated molecular pattern (MAMP) molecules, perceived by plant pattern recognition receptors (PRRs). Currently, the identified fungal MAMP molecules include chitin, chitosan, β-glucans, elicitins and ergosterol. Although the molecular battles between host plants and infecting fungal phytopathogens have been studied extensively, many aspects still need to be investigated to obtain a holistic understanding of the intrinsic mechanisms, which is paramount in combating fungal plant diseases. Here, an overview is given of the most recent findings concerning an 'orphan' fungal MAMP molecule, ergosterol, and we present what is currently known from a synopsis of different genes, proteins and metabolites found to play key roles in induced immune responses in plant-fungus interactions. Clearly, integrative investigations are still needed to provide a comprehensive systems-based understanding of the dynamics associated with molecular mechanisms in plant-ergosterol interactions and associated host responses.
Topics: Ergosterol; Fungi; Immunity, Innate; Plants; Signal Transduction
PubMed: 24528492
DOI: 10.1111/mpp.12127 -
Biomolecules Sep 2019, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader...
, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from (Jacq) P. Kumm. f. sp. Florida.
Topics: Cell Membrane; Crystallography, X-Ray; Cytochrome P-450 Enzyme System; Cytoplasm; Ergosterol; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Pleurotus; Trypanosoma cruzi
PubMed: 31547423
DOI: 10.3390/biom9090484 -
Food Research International (Ottawa,... Jul 2022Bisphenol A (BPA) has been reported to have neurotoxic properties that may increase the risk of neurodegenerative diseases by inducing neuroinflammation. Auricularia...
Bisphenol A (BPA) has been reported to have neurotoxic properties that may increase the risk of neurodegenerative diseases by inducing neuroinflammation. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced inflammation of BV2 microglial cells were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 microglia by reducing microglial activation and the expression of pro-inflammatory cytokines. These anti-inflammatory effects were regulated by the NF-κB signaling pathway. In addition, APH and APE exhibited antioxidative effects by increasing the activity of the SOD-1 enzyme and restoring the accumulation of reactive oxygen species (ROS) in BPA-induced BV2 cells. Moreover, the conditioned medium prepared using BPA-induced BV2 cells demonstrated that the presence of APH or APE could attenuate ROS production in HT-22 cells. Further, ergosterol was isolated from APE and also showed anti-inflammatory and antioxidative activities. In conclusion, AP extracts and ergosterol attenuated neuroinflammation against BPA induction in BV2 microglial cells through the NF-κB signaling pathway.
Topics: Agaricales; Anti-Inflammatory Agents; Auricularia; Benzhydryl Compounds; Ergosterol; Inflammation; Microglia; NF-kappa B; Phenols; Reactive Oxygen Species
PubMed: 35761673
DOI: 10.1016/j.foodres.2022.111433 -
European Journal of Pharmacology Oct 2019Ergosterol peroxide has been shown to exhibit anti-tumor, antioxidant and anti-bacterial properties. However, the effects of ergosterol peroxide isolated from the herbal...
Ergosterol peroxide has been shown to exhibit anti-tumor, antioxidant and anti-bacterial properties. However, the effects of ergosterol peroxide isolated from the herbal Baphicacanthus cusia root on influenza virus infection remain poorly understood. In the present study, ergosterol peroxide (compound 22) was obtained from the B. cusia root and subjected to investigation regarding its immunoregulatory effect on influenza A virus (IAV)-induced inflammation in A549 human alveolar epithelial cells. The structure of compound 22 isolated from B. cusia root. was elucidated by NMR analyses. Structure determination showed that the chemical structure of compound 22 closely resembles that of ergosterol peroxide. We observed that ergosterol peroxide treatment significantly suppressed IAV-induced upregulation of RIG-I expression. Additionally, ergosterol peroxide inhibited the activation of RIG-I downstream signaling pathways, including p38 MAP kinase and NF-κB, which ultimately resulted in the reduced production of an array of pro-inflammatory mediators and interferons (IFN-β and IFN-λ1). Interestingly, inhibitory effects of ergosterol peroxide on the expression of IFNs did not affect the expression of antiviral effectors or enhance viral replication. On the other hand, ergosterol peroxide effectively abolished the amplified production of pro-inflammatory mediators in cells pretreated with IFN-β (500 ng/ml) prior to IAV infection. Moreover, Annexin V and Hoechst 33258 staining revealed that increased apoptosis of IAV-infected cells was reversed by the presence of ergosterol peroxide. Our findings suggest that ergosterol peroxide from the B. cusia root suppressed IAV-associated inflammation and apoptosis via blocking RIG-I signaling, which may serve as a supplementary approach to the treatment of influenza.
Topics: A549 Cells; Animals; Apoptosis; DEAD Box Protein 58; Dogs; Ergosterol; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Influenza A Virus, H1N1 Subtype; Interferons; Madin Darby Canine Kidney Cells; Receptors, Immunologic; Signal Transduction
PubMed: 31323223
DOI: 10.1016/j.ejphar.2019.172543 -
Natural Product Research Dec 2021Two new ergosterol derivatives namely, chlamydosterols A [(22,24)-ergosta-7,22-diene-3β,5α,6β-triol 6-decanoate] () and B...
Two new ergosterol derivatives namely, chlamydosterols A [(22,24)-ergosta-7,22-diene-3β,5α,6β-triol 6-decanoate] () and B [5α,6β,25-trihydroxy-(22,24)-ergosta-7,22-dien-3-one] ( and three known ergosterols: ergosta-7,22-dien-3β-ol (), ergosta-5,7,22-triene-3β-ol (), and ergosta-7,22-diene-3,5α,6β-triol ( were separated from the EtOAc extract of the endophytic fungus isolated from (Asteraceae) leaves growing in Saudi Arabia. Their structural assignment was accomplished by various spectroscopic analyses, as well as comparing with the published data. The 5-lipoxygenase (5-LOX) inhibitory potential of the isolated metabolites was assessed. Compounds and displayed moderate 5-LOX inhibitory potential with ICs 3.06 and 3.57 µM, respectively compared to indomethacin (IC 1.13 µM).
Topics: Anti-Inflammatory Agents; Ergosterol; Fungi; Fusarium; Molecular Structure
PubMed: 32375510
DOI: 10.1080/14786419.2020.1762185 -
Organic & Biomolecular Chemistry May 2019Ergosterol peroxide selectively exhibits biological activity against a wide range of diseases; however, its mode of action remains unknown. Here, we present an efficient...
Ergosterol peroxide selectively exhibits biological activity against a wide range of diseases; however, its mode of action remains unknown. Here, we present an efficient synthesis of ergosterol peroxide chemical probes for in vitro anticancer evaluation, live cell studies and proteomic profiling. Ergosterol peroxide analogues show promising anti-proliferation activity against triple negative breast cancer cellular models, revealing information on the structure-activity relationship of this natural product in order to develop superior analogues. The combined cellular studies demonstrate that ergosterol peroxide is distributed across the cytosol with significant accumulation in the endoplasmic reticulum (ER). These chemical probes support our efforts towards uncovering the potential target(s) of ergosterol peroxide against triple negative breast cancer cell lines.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Ergosterol; Fluorescent Dyes; Humans; Microscopy, Fluorescence; Molecular Conformation; Optical Imaging; Triple Negative Breast Neoplasms
PubMed: 31025693
DOI: 10.1039/c9ob00145j -
Chemistry and Physics of Lipids Mar 2020Sterols regulate several physico-chemical properties of biological membranes that are considered to be linked to function. Ergosterol is the main sterol molecule found...
Sterols regulate several physico-chemical properties of biological membranes that are considered to be linked to function. Ergosterol is the main sterol molecule found in the cell membranes of yeasts and other fungi. Like the cholesterol found in mammalian cells, ergosterol has been proposed to have an ordering and condensing effect on saturated phospholipid membranes. The effects of cholesterol have been investigated extensively and result in an increase in the membrane thickness and the lipid acyl chain order. Less information is available on the effects of ergosterol on phospholipid membranes. Neutron Diffraction (ND) was used to characterize the effect of ergosterol on lipid multilayers prepared with deuterated natural phospholipids extracted from the yeast Pichia pastoris. The data show that the effect of ergosterol on membranes prepared from the natural phospholipid extract rich in unsaturated acyl chains, differs from what has been observed previously in membranes rich in saturated phospholipids. In contrast to cholesterol in synthetic phospholipid membranes, the presence of ergosterol up to 30 mol % in yeast phospholipid membranes only slightly altered the multilayer structure. In particular, only a small decrease in the multilayer d-spacing was observed as function of increasing ergosterol concentrations. This result highlights the need for further investigation to elucidate the effects of ergosterol in biological lipid mixtures.
Topics: Deuterium; Ergosterol; Lipid Bilayers; Neutron Diffraction; Phospholipids; Pichia
PubMed: 31926858
DOI: 10.1016/j.chemphyslip.2020.104873 -
International Journal of Molecular... Jan 2020Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral...
Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipokines; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cell Survival; Down-Regulation; Ergosterol; Lipid Metabolism; Lipogenesis; Mice; PPAR gamma; Phosphorylation; Reishi; Sterol Regulatory Element Binding Protein 1; Triglycerides
PubMed: 31936890
DOI: 10.3390/ijms21020460 -
The Journal of Physical Chemistry. B Jul 2019The sterol ergosterol (Erg) is ubiquitous in the membranes of lower eukaryotes such as fungi. To investigate the interactions between Erg and phosphocholine (PC)...
The sterol ergosterol (Erg) is ubiquitous in the membranes of lower eukaryotes such as fungi. To investigate the interactions between Erg and phosphocholine (PC) molecules, we studied ternary lipid mixture systems composed of unsaturated 1,2-dioleoyl--glycero-3-phosphocholine (DOPC), saturated 1,2-dipalmitoyl--glycero-3-phophocholine (DPPC), and Erg. Bilayer membrane fluidity and polarity were systematically analyzed using fluorescent probes. The presence of ≥30 mol % of Erg exhibited a significant ordering effect and stabilized membrane properties when temperatures increased, suggesting that Erg has a similar function to cholesterol (Chol) in comparable lipid systems that form a liquid-ordered phase. Erg was also observed to have a significant condensing effect at the monolayer level in saturated PC-enriched systems. The phase behavior of Erg in bilayer systems was compared with that of Chol, with the data suggesting that Erg behaves in a similar manner to Chol in membranes enriched with saturated lipids.
Topics: Cell Membrane; Cholesterol; Ergosterol; Phospholipids
PubMed: 31260623
DOI: 10.1021/acs.jpcb.9b03413