Isolation and Identification of Endophytic Fungi from Syzygium cumini Linn and Investigation of Their Pharmacological Activities.

This study was conducted to isolate and identify the endophytic fungi from the bark and leaves of the Syzygum cumini plant and investigate the pharmacological activities of endophytic fungi along with plant parts. After isolation, endophytic fungi were identified based on morphological characteristics and molecular identification. Antimicrobial, antioxidant, and cytotoxic activities were studied by a disc diffusion method, free radical scavenging DPPH assay, and brine shrimp lethality bioassay, respectively. A total of eight endophytic fungi were isolated and identified up to the genus level based on morphological characteristics and confirmed by molecular identification techniques. Among the eight isolates, three isolates were identified as Colletotrichum sp. (SCBE-2, SCBE-7, and SCLE-9), while the rest of the isolates belonged to Diaporthe sp. (SCBE-1), Pestalotiopsis sp. (SCBE-3), Penicillium sp. (SCBE-4), Phyllosistica sp. (SCLE-7), and Fusarium sp. (SCLE-8). The presence of flavonoids, anthraquinones, coumarins, and isocoumarins was assumed by the preliminary screening of the fungal and plant extracts by a thin-layer chromatographic technique under UV light. Fungal extracts of Pestalotiopsis sp. Penicillium sp. were found sensitive to all test bacteria, but only extracts from the leaf and bark showed significant antifungal activity along with their antimicrobial activity. Penicillium sp. The fungal extract showed the highest free radical scavenging activity (2.43 µg/mL) near that of ascorbic acid (2.42 µg/mL). Some fungal extracts showed cytotoxic activity that, in general, suggests their probable abundance of biological metabolites. This is the first approach to investigate the endophytic fungi of Syzygium cumini Linn. in Bangladesh, to find the pharmacological potential of endophytes, and to explore novel compounds from those endophytes.

Physicochemical, Pharmacokinetic and Cytotoxicity of the Compounds Isolated from an Endophyte Fusarium oxysporum: In Vitro and In Silico Approaches.

The present study was intended to characterize the secondary metabolites of the endophyte Fusarium oxysporum isolated from the plant Aglaonema hookerianum Schott. And to investigate the cytotoxic and other pharmacological properties of the isolated compounds as part of the drug discovery and development process. Different chromatographic techniques were adopted to isolate the bioactive compounds that were identified by spectroscopic techniques. The cytotoxic properties of the compounds were assessed in the Vero cell line via the trypan blue method. Moreover, physicochemical, pharmacokinetic, bioactivity and toxicity profiles of the compounds were also investigated through in silico approaches. After careful spectral analysis, the isolated compounds were identified as 3ß,5α-dihydroxy-ergosta-7,22-dien-6-one (1), 3ß,5α,9α-trihydroxy-ergosta-7,22-dien-6-one (2), p-hydroxybenzaldehyde (3), 3-(R)-7-butyl-6,8-dihydroxy-3-pent-11-enylisochroman-1-one (4) and beauvericin (5). An in vitro study in the Vero cell line revealed that the presence of the compounds reduced the number of cells, as well as the percentage of viable cells, in most cases. An in silico cytotoxic analysis revealed that compounds 1, 2 and 5 might be explored as cytotoxic agents. Moreover, compounds 3 and 4 were found to be highly mutagenic. The present study suggested that further thorough investigations are necessary to use these molecules as leads for the cytotoxic drug development process.

Intervention in Neuropsychiatric Disorders by Suppressing Inflammatory and Oxidative Stress Signal and Exploration of In Silico Studies for Potential Lead Compounds from Holigarna caustica (Dennst.) Oken leaves.

Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management of neuropsychiatric disorders. The methanol extract of H. caustica leaves (MEHC) were utilized on various behavioral tests for assessing anxiolytic, anti-depressant, and anti-inflammatory activities. The antioxidant potentials and quantitative phytochemicals were evaluated through spectrophotometric methods. Results revealed that treatment of MEHC (200 and 400 mg/kg) significantly reduced anxiety like behaviors in mice, particularly, 400 mg/kg efficiently improved % of entries and time spent (p < 0.05) in the open arms in elevated plus maze test, whereas, superior head dipping tendency (p < 0.05) was observed in hole-board test. In contrast, mice treated with 200 mg/kg revealed better anxiolytic effect in both open field and hole-cross tests. During antidepressant evaluation, mice administrated with MEHC exhibited active behaviors (swimming and struggling) in forced swimming and tail suspension tests. In parallel, MEHC manifested a noteworthy (p < 0.001) suppression of inflammatory response induced by histamine. The MEHC also showed strong antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (IC50: 57.64 µg/mL) scavenging, H2O2 (IC50: 51.60 µg/mL) scavenging, and ferric reducing power assay. The levels of total phenol, flavonoid, flavonol, condensed tannin, and antioxidant were estimated as higher in MEHC. Moreover, 11 compounds were documented as bioactive, displayed good binding affinities to potassium channel receptor, human serotonin receptor, cyclooxygenase (COX-1 and 2), and xanthine oxidoreductase enzyme targets in molecular docking experiments. Furthermore, ADME/T and Prediction of Activity Spectra for Substances (PASS) analyses exposed their drug-likeness, nontoxic upon consumption, and likely pharmacological actions. Overall, the H. caustica is potentially bioactive as evident by in vivo, in vitro, and computational analysis. Our findings support the folkloric value of this plant, which may provide a potential source towards developing drug leads.

Cytotoxic and antibacterial naphthoquinones from an endophytic fungus, Cladosporium sp.

OBJECTIVE: Endophytes have the potential to synthesize various bioactive secondary metabolites. The aim of the study was to find new cytotoxic and antibacterial metabolites from endophytic fungus, Cladosporium sp. isolated from the leaves of Rauwolfia serpentina (L.) Benth. ex Kurz. (Fam: Apocyanaceae). MATERIALS AND METHODS: The endophytic fungus was grown on potato dextrose agar medium and extracted using ethyl acetate. Secondary metabolites were isolated by chromatographic separation and re-crystallization, and structures were confirmed by 1H NMR, 13C NMR and mass spectroscopic data. The cytotoxicity was determined by WST-1 assay and brine shrimp lethality bioassay, while antibacterial activity was assessed by disc diffusion method. RESULTS: Two naphthoquinones, namely anhydrofusarubin (1) and methyl ether of fusarubin (2), were isolated from Cladosporium sp. The isolated compounds 1 and 2, by WST-1 assay against human leukemia cells (K-562) showed potential cytotoxicity with IC50 values of 3.97 µg/mL and 3.58 µg/mL, respectively. Initial screening of crude ethyl acetate extract and column fractions F-8 and F-10 exhibited noticeable cytotoxicity to brine shimp nauplii with LC50 values of 42.8, 1.2 and 2.1 µg/mL, respectively. Moreover, the isolated compound 2 (40 µg/disc) showed prominent activities against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus megaterium with an average zone of inhibition of 27 mm, 25 mm, 24 mm and 22 mm, respectively and the activities were compared with kanamycin (30 µg/disc). CONCLUSION: Our findings indicate that anhydrofusarubin (1) and methyl ether of fusarubin (2) might be useful lead compounds to develop potential cytotoxic and antimicrobial drugs.