Polyenylpyrrole Derivatives Inhibit NLRP3 Inflammasome Activation and Inflammatory Mediator Expression by Reducing Reactive Oxygen Species Production and Mitogen-Activated Protein Kinase Activation

10.1371/journal.pone.0076754PLoS ONE810-POLN

Trypacidin, a Spore-Borne Toxin from Aspergillus fumigatus, Is Cytotoxic to Lung Cells

Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC50 close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H2O2). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported

Isolation, characterization, and bioactivity of endophytic fungi of Tylophora indica

Dothediomycetes sp., Alternaria tenuissima, Thielavia subthermophila, Alternaria sp., Nigrospora oryzae, Colletotrichum truncatum, and Chaetomium sp. were isolated as endophytic fungi from leaves and stems of the medicinal plant, Tylophora indica, based on rDNA sequencing of ITS region and microscopic examination. Alternaria tenuissima, Colletotrichum truncatum, and Alternaria sp. were found to be active against both Sclerotinia sclerotiorum and Fusarium oxysporum. Chaetomium sp. showed very mild activity against Sclerotinia sclerotiorum and Fusarium oxysporum. Whereas Dothideomycete sp. and Thielavia subthermophila showed high activity against Sclerotinia sclerotiorum. Methanol extract of Dothediomycetes sp. showed 66. 5% growth inhibition (GI) at 500 μg/ml