scholarly journals Twenty-Eight Fungal Secondary Metabolites Detected in Pig Feed Samples: Their Occurrence, Relevance and Cytotoxic Effects In Vitro

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 537 ◽  
Author(s):  
Barbara Novak ◽  
Valentina Rainer ◽  
Michael Sulyok ◽  
Dietmar Haltrich ◽  
Gerd Schatzmayr ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Analytical Techniques ◽  
Epithelial Cell Line ◽  
Cytotoxic Effects ◽  
Wide Range ◽  
Ic50 Values ◽  
Pig Feed ◽  
Feed Samples ◽  
Fungal Secondary Metabolites

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant concentrations. In our study, 1141 pig feed samples were analyzed for more than 800 secondary fungal metabolites using the same LC-MS/MS method and ranked according to their prevalence. Effects on the viability of the 28 most relevant were tested on an intestinal porcine epithelial cell line (IPEC-J2). The most frequently occurring compounds were determined as being cyclo-(L-Pro-L-Tyr), moniliformin, and enniatin B, followed by enniatin B1, aurofusarin, culmorin, and enniatin A1. The main mycotoxins, deoxynivalenol and zearalenone, were found only at ranks 8 and 10. Regarding cytotoxicity, apicidin, gliotoxin, bikaverin, and beauvericin led to lower IC50 values, between 0.52 and 2.43 µM, compared to deoxynivalenol (IC50 = 2.55 µM). Significant cytotoxic effects were also seen for the group of enniatins, which occurred in up to 82.2% of the feed samples. Our study gives an overall insight into the amount of fungal secondary metabolites found in pig feed samples compared to their cytotoxic effects in vitro.

Associated microflora of medicinal ferns: biotechnological potentials and possible applications

2016 ◽  
Vol 5 (03) ◽  
pp. 4927 ◽  
Author(s):  
Shubhi Srivastava ◽  
Paul A. K.
Keyword(s):  
Secondary Metabolites ◽  
Growth Promotion ◽  
Biological Activities ◽  
Hydrolytic Enzymes ◽  
In Vitro Production ◽  
Wide Range ◽  
Negative Effect ◽  
Bacteria And Fungi

Plant associated microorganisms that colonize the upper and internal tissues of roots, stems, leaves and flowers of healthy plants without causing any visible harmful or negative effect on their host. Diversity of microbes have been extensively studied in a wide variety of vascular plants and shown to promote plant establishment, growth and development and impart resistance against pathogenic infections. Ferns and their associated microbes have also attracted the attention of the scientific communities as sources of novel bioactive secondary metabolites. The ferns and fern alleles, which are well adapted to diverse environmental conditions, produce various secondary metabolites such as flavonoids, steroids, alkaloids, phenols, triterpenoid compounds, variety of amino acids and fatty acids along with some unique metabolites as adaptive features and are traditionally used for human health and medicine. In this review attention has been focused to prepare a comprehensive account of ethnomedicinal properties of some common ferns and fern alleles. Association of bacteria and fungi in the rhizosphere, phyllosphere and endosphere of these medicinally important ferns and their interaction with the host plant has been emphasized keeping in view their possible biotechnological potentials and applications. The processes of host-microbe interaction leading to establishment and colonization of endophytes are less-well characterized in comparison to rhizospheric and phyllospheric microflora. However, the endophytes are possessing same characteristics as rhizospheric and phyllospheric to stimulate the in vivo synthesis as well as in vitro production of secondary metabolites with a wide range of biological activities such as plant growth promotion by production of phytohormones, siderophores, fixation of nitrogen, and phosphate solubilization. Synthesis of pharmaceutically important products such as anticancer compounds, antioxidants, antimicrobials, antiviral substances and hydrolytic enzymes could be some of the promising areas of research and commercial exploitation.

scholarly journals Secondary metabolites of a marine-derived Penicillium ochrochloron

2021 ◽  
Vol 13 (3) ◽  
pp. 11020
Author(s):  
Peter M. EZE ◽  
Ying GAO ◽  
Yang LIU ◽  
Lasse Van GEELEN ◽  
Chika P. EJIKEUGWU ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Biological Properties ◽  
Industrial Applications ◽  
Biologically Active ◽  
Fungal Isolation ◽  
The North ◽  
Wide Range ◽  
Extremophilic Fungi ◽  
Fungal Secondary Metabolites

Extremophilic fungi have received considerable attention recently as new promising sources of biologically active compounds with potential pharmaceutical applications. This study investigated the secondary metabolites of a marine-derived Penicillium ochrochloron isolated from underwater sea sand collected from the North Sea in St. Peter-Ording, Germany. Standard techniques were used for fungal isolation, taxonomic identification, fermentation, extraction, and isolation of fungal secondary metabolites. Chromatographic separation and spectroscopic analyses of the fungal secondary metabolites yielded eight compounds: talumarin A (1), aspergillumarin A (2), andrastin A (3), clavatol (4), 3-acetylphenol (5), methyl 2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furanpropanoate (6), emodin (7) and 2-chloroemodin (8). After co-cultivation with Bacillus subtilis, the fungus was induced to express (-)-striatisporolide A (9). Compound 1 was evaluated for antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Mycobacterium smegmatis, and M. tuberculosis, as well as cytotoxicity against THP-1 cells. The compound, however, was not cytotoxic to THP-1 cells and had no antibacterial activity against the microorganisms tested. The compounds isolated from P. ochrochloron in this study are well-known compounds with a wide range of beneficial biological properties that can be explored for pharmaceutical, agricultural, or industrial applications. This study highlights the bioprospecting potential of marine fungi and confirms co-cultivation as a useful strategy for the discovery of new natural products.

Diallyl Disulfide Attenuates Methotrexate-Induced Hepatic Oxidative Injury, Inflammation and Apoptosis and Enhances its Anti-tumor Activity

2021 ◽  
Vol 14 ◽  
Author(s):  
Marwa M. Khalaf ◽  
Emad H.M. Hassanein ◽  
Abdel-Gawad S. Shalkami ◽  
Ramadan A.M. Hemeida ◽  
Wafaa R. Mohamed
Keyword(s):  
Cytotoxic Activity ◽  
Caspase 3 ◽  
In Vitro Study ◽  
Diallyl Disulfide ◽  
Sod Activity ◽  
Cytotoxic Effects ◽  
Wide Range ◽  
Anti Tumor Activity ◽  
Mcf 7

Background: Methotrexate (MTX) is used potently for a wide range of diseases. However, hepatic intoxication by MTX hinders its clinical use. Objectives: The present study was conducted to investigate the diallyl disulfide (DADS) ability to ameliorate MTX-induced hepatotoxicity. Methods: Thirty-two rats were randomly divided into four groups: normal control, DADS (50 mg/kg/day, orally), MTX (single i.p. injection of 20 mg/kg) and DADS+MTX. Liver function biomarkers, histopathological examinations, oxidative stress, inflammation, and apoptosis biomarkers were investigated. Besides, an in vitro cytotoxic activity study was conducted to explore the modulatory effects of DADS on MTX cytotoxic activity using Caco-2, MCF-7, and HepG2 cells. Results: DADS significantly reduced the increased serum activities of ALT, AST, ALP, and LDH. These results were confirmed by the alleviation of liver histopathological changes. It restored the decreased GSH content and SOD activity, while significantly decreased MTX-induced elevations in both MDA and NO2- contents. The hepatoprotective effects were mechanistically mediated through the up-regulation of hepatic Nrf-2 and the down-regulation of Keap-1, P38MAPK, and NF-κB expression levels. In addition, an increase in Bcl-2 level with a decrease in the expression of both Bax and caspase-3 was observed. The in vitro study showed that DADS increased MTX anti-tumor efficacy. Conclusions: DADS potently alleviated MTX-induced hepatotoxicity through the modulation of Keap-1/Nrf-2, P38MAPK/NF-κB and apoptosis signaling pathways and effectively enhanced the MTX cytotoxic effects, which could be promising for further clinical trials.

Comparative Analysis of in Vitro Chemosensitivity to Four Proteasome Inhibitors in Human Myeloma Cell Lines

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3436-3436
Author(s):  
Amit Kumar Mitra ◽  
Taylor S Harding ◽  
Brian Van Ness
Keyword(s):  
Multiple Myeloma ◽  
Cell Viability ◽  
Cell Lines ◽  
Proteasome Inhibitors ◽  
Genetic Characteristics ◽  
Myeloma Cells ◽  
In Vitro Chemosensitivity ◽  
Wide Range ◽  
Ic50 Values

Abstract Proteasome inhibitors (PI) are effective chemotherapeutic agents in the treatment of multiple myeloma (MM), used alone or in combination with other anti-cancer agents, such as alkylating agents, topoisomerase inhibitors, corticosteroids, histone deacetylase inhibitors (HDACis) and immunomodulatory drugs (IMiDs). Bortezomib (Velcade/Bz) was the first PI to be approved by US-FDA for the treatment of relapsed and refractory MM. Other second generation PIs include carfilzomib (Kyprolis/Cz), ixazomib/Iz and oprozomib (Opz). Wide inter-individual variation in response to treatment with PIs is a major limitation in achieving consistent therapeutic effect in MM. Yet few studies have compared the efficacy of all four PIs in a range of myeloma subtypes. In our current study, we performed comprehensive in vitro chemosensitivity profiling of response to four (4) PIs (Bz, Cz, Ix and Opz) in a panel of forty-five (45) human myeloma cells lines (HMCLs) generated through the immortalization of primary multiple myeloma cells (MMCs) and representing the biological and genetic heterogeneity of MM with regards to chromosomal abnormalities, oncogene mutations (e.g. Ras), tumor suppressor variations (e.g. p53), cell surface phenotypes, or growth factor response. Cells were treated with increasing concentrations of Bz, Cz, Ix and Opz as single agents and cell viability assays were performed using CellTiter-Glo luminescent cell viability assay to generate survival curves and determine the half maximal inhibitory concentration (IC50) values by calculating the nonlinear regression using sigmoidal dose-response equation (variable slope). Our results in comparing the cellular responses to PI treatment among HMCLs showed wide range of variability in IC50 values identifying some lines which were highly sensitive and some lines relatively refractory to PI treatment. Pearson product-moment correlation (PPMC) test demonstrated statistically significant (adjusted p values < 0.001) positive correlation between IC50 values of the following drug pairs: Bz vs Opz (r = 0.82); and Ix vs Opz (r = 0.88); Bz vs Ix (r = 0.65); Cz vs Opz (r = 0.69) and Cz vs Ix (r = 0.63). Subgroup analysis revealed significant correlation between carfizomib IC50 and chromosome number (p < 0.05). Furthermore, it was interesting to note that although all 4 drugs belong to the same drug class (PI), not all cell lines responded the same across all PI treatments. This demonstrates tumor heterogeneity even in response to inhibitors of the same class, and further demonstrates tumors refractory to one PI may still respond to another. We are currently examining genetic characteristics that are associated with response among the four PIs, and analysis of these characteristics will be presented. Disclosures No relevant conflicts of interest to declare.

Multi-mycotoxin screening of feed and feed raw materials from Africa

2018 ◽  
Vol 11 (3) ◽  
pp. 369-383 ◽  
Author(s):  
C. Gruber-Dorninger ◽  
T. Jenkins ◽  
G. Schatzmayr
Keyword(s):  
South Africa ◽  
Secondary Metabolites ◽  
Cote D'ivoire ◽  
Côte D’Ivoire ◽  
Raw Materials ◽  
Fusarium Mycotoxins ◽  
Cote D’Ivoire ◽  
High Concentrations ◽  
Feed Samples ◽  
Fungal Secondary Metabolites

As animal feed is prone to infestation with mycotoxin-producing fungi, mycotoxin contamination of feed should be monitored. Here, we report a multi-mycotoxin survey of feed samples from Africa. We determined the concentrations of aflatoxins, fumonisins, deoxynivalenol, T-2 toxin, zearalenone and ochratoxin A in 1,045 samples of finished feed and feed raw materials (maize, maize silage, other cereals, etc.) from South Africa and 318 samples from Algeria, Tunisia, Morocco, Senegal, Côte d’Ivoire, Nigeria, Ghana, Namibia, Uganda, Kenya, Tanzania, Zambia and Madagascar. We compared the measured mycotoxin concentrations to regulatory limits or guidance values that are in effect in the European Union and analysed the co-occurrence of these mycotoxins. To determine the occurrence of other fungal secondary metabolites, a subset of the samples was analysed using a multi-analyte liquid chromatography tandem mass spectrometry-based method for the simultaneous detection of over 700 fungal metabolites. We found that 33.3% of maize samples and 54.4% of finished feed samples from Senegal, Côte d’Ivoire, Nigeria, Ghana, Namibia, Uganda, Kenya and Tanzania exceeded the European regulatory limit of 20 ng/g aflatoxins. The Fusarium mycotoxins zearalenone, fumonisins and deoxynivalenol were prevalent in all commodities from all countries, but concentrations were in most cases below European guidance values. Concentrations of deoxynivalenol and zearalenone were correlated. Several other Fusarium metabolites occurred frequently (e.g. moniliformin, beauvericin, aurofusarin) or in high concentrations (e.g. aurofusarin, fusaproliferin). Furthermore, high levels of diplodiatoxin were occasionally detected in samples from South Africa and the Alternaria metabolite tenuazonic acid was prevalent and reached high concentrations. In conclusion, aflatoxins frequently occurred in African feed samples in potentially unsafe concentrations. While Fusarium mycotoxins mostly occurred in concentrations below European guidance values, a correlation between deoxynivalenol and zearalenone concentrations suggests that toxicological interactions of these compounds deserve attention. Several less investigated fungal secondary metabolites occurred frequently or reached high concentrations.

scholarly journals New Bioactive Sesquiterpeniods From the Plant Endophytic Fungus Pestalotiopsis theae

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoran Liu ◽  
Ruiyun Huo ◽  
Yanan Zhai ◽  
Ling Liu
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Cell Lines ◽  
Crude Extract ◽  
Endophytic Fungus ◽  
Spectroscopic Data ◽  
Mcf7 Cell ◽  
Cytotoxic Effects ◽  
Electronic Circular Dichroism

Three new secondary metabolites pestalothenins A–C (1–3), including two new humulane-derived sesquiterpeniods (1 and 2) and one new caryophyllene-derived sesquiterpeniod (3), together with five known compounds (4–8) were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). Their structures were elucidated by the extensive analyses of HRESIMS and NMR spectroscopic data. The absolute configurations of 1–3 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The cytotoxic effects of these compounds were evaluated in vitro. Compound 6 showed moderate cytotoxicity against T24 and MCF7 cell lines. In addition, compounds 1–8 were also evaluated for antibacterial activity.

scholarly journals Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5226
Author(s):  
Yi-Fei Gu ◽  
Yue Zhang ◽  
Feng-li Yue ◽  
Shao-tong Li ◽  
Zhuo-qi Zhang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Collagen Type I ◽  
Type I ◽  
The Novel ◽  
Pyrimidine Derivatives ◽  
Wide Range ◽  
Ic50 Values ◽  
Privileged Structures ◽  
Pyrimidine Moiety

A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC50 values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.

In Vivo and In Vitro Production Options for Fungal Secondary Metabolites

2008 ◽  
Vol 5 (2) ◽  
pp. 234-242 ◽  
Author(s):  
Patrick Schneider ◽  
Mathias Misiek ◽  
Dirk Hoffmeister
Keyword(s):  
Secondary Metabolites ◽  
In Vitro Production ◽  
Vitro Production ◽  
Fungal Secondary Metabolites

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23

Planta Medica ◽  
2020 ◽  
Vol 86 (13/14) ◽  
pp. 976-982
Author(s):  
Ying Gao ◽  
Jia Zhou ◽  
Hanli Ruan
Keyword(s):  
Endophytic Fungus ◽  
In Vitro Cytotoxicity ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Effects ◽  
Ic50 Values ◽  
Alternaria Sp ◽  
Optical Rotations ◽  
Ht 29 ◽  
Necrosis Factor

AbstractThree new (alterchothecenes A – C, 1 –3) and 3 known (4 –6) trichothecenes, along with 9 known compounds (7 –15), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1–3 were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1–6 against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4–6 exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1–6 as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1–6 synergistically decreased cell viability compared with the sole treatment with those compounds.

scholarly journals In vitro Antibacterial Potential of Halophilic Bacterial Secondary Metabolites from Salted Fish

2016 ◽  
Vol 8 (04) ◽  
Author(s):  
G. Prakash Williams ◽  
Anju Anand ◽  
Parvathy A. ◽  
Rakky C. Raj ◽  
Robert Raju ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Xanthomonas Campestris ◽  
Halophilic Bacteria ◽  
Resistance Pattern ◽  
Salted Fish ◽  
Wide Range ◽  
Fish Samples

Living organisms can be found over a wide range of extreme conditions. Most of the organisms living in extreme environments (i.e, extremophiles) belong to the prokaryotes. Halophiles are interesting class of extremophilic organisms that have adapted to harsh, hypersaline conditions. They are able to compete successfully for water and resist the denaturing effects of salts. The present study was an investigation on the in vitro antibacterial effect of secondary metabolites from halophilic bacteria isolated from salted fish samples. The cured salted fish samples were collected and enumerated using halophilic Nutrient Agar supplemented with 4% NaCl. The isolated and purified bacterial cultures are numbered as SF1, SF2, SF3, SF4 and SF5 are further identified using VITEK 2 system as Bacillus vallismortis, Ralstonia mannitolytica, Bacillus subtilis, Rhizoboum radiobacter and Kocuria kristina. Growth kinetics of halobacterial isolates were determined by spectrophotometric assay. The antibiotic resistance pattern of tested pathogenic microorganisms using the commercial antibiotics was screened and almost all the tested microorganisms are resistant to Penicillin. The antimicrobial activity of secondary metabolites of halophilic bacteria against drug resistant microbes was assessed using the Agar well diffusion assay. Among the different extracts of the halophilic bacteria, the chloroform extracts of R. mannitolytica showed maximum antibacterial activity against Bacillus subtilis MTCC 441 and Xanthomonas campestris MTCC 2286. The results of antimicrobial activity are considerable because it enables the identification of potential secondary metabolites present in marine halophilic bacteria, which act as source of innumerable therapeutic agents. Further research is highly warranted to find out the active principle responsible for the antibacterial property and to elucidate the structure of particular compound.

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