Copper oxide nanoparticles synthesized from an endophytic fungus Aspergillus terreus: Bioactivity and anti-cancer evaluations.

The mycofabricated metal nanoparticles (NPs) plays a significant role in cancer therapeutics and imparts a strategy in medicine. The current investigation focused to synthesize the Copper Oxide Nanoparticles (CuONPs) using an endophytic fungus isolated from Aegle marmelosa medicinal tree located in Western Ghats, India. The endophytic fungus FCBY1 explored the highest antagonistic and antioxidant activities among the 16 pigmented endophytic fungal strains which were isolated from the collected samples. The fungus FCBY1 was identified for its morphological and molecular characteristics where the (Internal Transcribed Spacer) ITS 1, 5.8 ribosomal gene and ITS 2 were sequenced; and the organism FCBY1 is Aspergillus terreus. The endophyte was put through for the synthesis of CuONPs and the size and structure of the synthesized particles were characterized by Scanning Electron Microscope (SEM). The confirmation of the CuONPs was characterized by FT-IR, EDAX and XRD analyses. The CuONPs exhibited the maximized antibacterial and antifungal activities against the human clinical pathogens; moreover the particles also explicated the free radicals/ROS scavenging at minimum concentration, which was assessed through DPPH, nitric oxide radical scavenging assays, and reductive power ability. The anti-cancer activity of CuONPs on colon cancer cell lines (HT-29) was evaluated by MTT (IC50: 22 µg/mL) and FACS analyses (32.11% cells gated in S phase of cell cycle). Angiogenesis inhibition in tumor cells was estimated through in vivo HET- CAM assessment and the highest concentration 60 µL tested inhibited the blood vessels at the percentage of 31.36% and 81.81%. The CuONPs explicated the anti-cancer activities in a concentration - dependent manner and the results of this investigation manifest the significant role of the CuONPs in cancer therapeutics.

Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models.

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen's Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

Bioprospecting Endophytic Fungi and Their Metabolites from Medicinal Tree Aegle marmelos in Western Ghats, India.

The increasing emergence of lead drugs for the resistance produced by the pathogenic strains and arrival of new diseases have initiated the need for searching novel metabolites with best anticancer and antimicrobial properties than the existing one. With this view, the investigation was conducted for the isolation, identification, and biological evaluation of potential endophytic fungi of Aegle marmelos, a medicinal tree used for more than three decades, for curing various disorders. A total of 169 endophytic fungal strains obtained from sampling and among those 67 were pigmented strains. Upon antagonistic screening, five endophytic fungal strains exhibited antagonistic potentiality by inhibiting the pathogens. These five potent strains were characterized at molecular level by sequencing the amplified internal transcribed spacer (ITS) 1 and ITS 4 regions of rDNA and they were grouped under order Pleosporales, Eurotiales, and Capnodiales. The metabolites from the respective strains were produced in fungal culturing media and extracted using polar solvents. Further, the extracts of five endophytes manifested antimicrobial activity against tested clinical pathogens and Alternaria alternata (FC39BY), Al. citrimacularis (FC8ABr), and Curvularia australiensis (FC2AP) exhibited significant antimicrobial profile against 9 of 12 tested pathogens, showing broad spectrum activity. The antioxidant levels of all the five endophytes revealed the highest activity at least concentrations, and major activity was unveiled by the members of order Pleosporales FC2AP and FC8ABr. This research explains the value of endophytic fungal extracts and its significance of antimicrobial and antioxidant properties.