Antimicrobial, antioxidant, and cytotoxic properties of endophytic fungi isolated from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott.

BACKGROUND: Endophytic fungi have recently been recognized as an impressive source of natural biomolecules. The primary objective of the research was to isolate fungal endophytes from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott. of Bangladesh and assess their pharmacological potentialities focusing on antimicrobial, antioxidant, and cytotoxic properties. METHODS: The fungal isolates were identified up to the genus level by analyzing their macroscopic and microscopic characteristics. Ethyl acetate extracts of all the fungal isolates were screened for different bioactivities, including antimicrobial (disc diffusion method), antioxidant (DPPH scavenging assay), and cytotoxic (brine shrimp lethality bioassay) activities. RESULTS: Among the thirteen isolates, Fusarium sp. was the most recognized genus, while the others belonged to Colletotrichum sp. and Pestalotia sp. Comparing the bioactivity of all the extracts, Fusarium sp. was shown to be the most effective endophyte, followed by Colletotrichum sp. and Pestalotia sp. In the antimicrobial study, two isolates of Fusarium sp. (internal strain nos. DSLE-1 and AHPE-4) showed inhibitory activity against all the tested bacteria and the highest zone of inhibition (15.5 ± 0.4 mm) was exerted by AHPE-4 against Bacillus subtillis. All the fungal isolates produced mild to moderate free radical scavenging activity, where the highest antioxidant activity was revealed by one isolate of Fusarium sp. (internal strain no. AHPE-3) with an IC50 value of 84.94 ± 0.41 µg/mL. The majority of Fusarium sp. isolates exhibited notable cytotoxic activity, where AHPE-4 exhibited the highest cytotoxicity, having the LC50 value of 14.33 ± 4.5 µg/mL. CONCLUSION: The findings of the study endorsed that the fungal endophytes isolated from T. maxima, D. spicata, and A. hookerianum hold potential as valuable origins of bioactive substances. Nevertheless, more comprehensive research is warranted, which could develop novel natural compounds from these endophytes to treat various infectious and cancerous diseases.

Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach.

Breast cancer has historically been one of the leading causes of death for women worldwide. As of 2020, breast cancer was reported to have overtaken lung cancer as the most common type of cancer globally, representing an estimated 11.3% of all cancer diagnoses. A multidisciplinary approach is taken for the diagnosis and treatment of breast cancer that includes conventional and targeted treatments. However, current therapeutic approaches to treating breast cancer have limitations, necessitating the search for new treatment options. Cancer cells require adequate iron for their continuous and rapid proliferation. Excess iron saturates the iron-binding capacity of transferrin, resulting in non-transferrin-bound iron (NTBI) that can catalyze free-radical reactions and may lead to oxidant-mediated breast carcinogenesis. Moreover, excess iron and the disruption of iron metabolism by local estrogen in the breast leads to the generation of reactive oxygen species (ROS). Therefore, iron concentration reduction using an iron chelator can be a novel therapeutic strategy for countering breast cancer development and progression. This review focuses on the use of iron chelators to deplete iron levels in tumor cells, specifically in the breast, thereby preventing the generation of free radicals. The inhibition of DNA synthesis and promotion of cancer cell apoptosis are the targets of breast cancer treatment, which can be achieved by restricting the iron environment in the body. We hypothesize that the usage of iron chelators has the therapeutic potential to control intracellular iron levels and inhibit the breast tumor growth. In clinical settings, iron chelators can be used to reduce cancer cell growth and thus reduce the morbidity and mortality in breast cancer patients.

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.

Fusaproliferin, a Fungal Mycotoxin, Shows Cytotoxicity against Pancreatic Cancer Cell Lines.

As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from a Fusarium solani strain, which is associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell lines. Time-dependent survival analysis and microscopy imaging showed rapid morphological changes in cancer cell lines 4 h after incubation with FUS. This provides a new chemical scaffold that can be further developed to obtain more potent synthetic agents against pancreatic cancer.

Protective effect of chloroform extract of Stereospermum chelonoides bark against amyloid beta42 induced cell death in SH-SY5Y cells and against inflammation in Swiss albino mice.

Background This study was designed to evaluate the free radical scavenging property of chloroform extract of the bark of Stereospermum chelonoides (SCBC) and to investigate its potential in Alzheimer's disease and inflammation, two oxidative stress related disorders. Methods Preliminary phytochemical analysis and in vitro antioxidant potential of SCBC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, cupric reducing antioxidant capacity (CUPRAC) and total antioxidant capacity determination assay. Total phenol and total flavonoid contents were also determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and cyto-protective assays were performed on human neuroblastoma SH-SY5Y cells. Thioflavin-T assay and caspase activation measurement assay were carried out to elucidate the mechanism of cytoprotection of SCBC observed here. In vivo anti-inflammatory potential was measured using croton oil and xylene induced ear edema tests. Results Phytochemical screening of SCBC revealed the presence of various phytoconstituents. Dose-dependent in vitro antioxidant activity was observed. The extract was enriched in flavonoids and polyphenolic compounds too. SCBC was found to inhibit amyloid-ß peptide 1-42 (Aß42) induced cell death in a dose-dependent manner. Encouraged by the cyto-protective effect, its effects on Aß42 fibrillogenesis and caspase-3 activated apoptosis were observed. SCBC significantly slowed down the Aß42 fibrillogenesis and caspase-3 activation in a concentration-dependent manner indicating its probable mechanism of rendering cyto-protection. SCBC has been able to reduce inflammation significantly in croton oil induced ear edema in both doses. Conclusions Thus, this study could form the basis for further study for the potential use of SCBC in oxidative stress associated cell death and inflammation.

A survey of medicinal plants used by the Deb barma clan of the Tripura tribe of Moulvibazar district, Bangladesh.

BACKGROUND: The number of tribes present within Bangladesh has been estimated to approximate one hundred and fifty. Information on traditional medicinal practices, particularly of the smaller tribes and their clans is lacking. It was the objective of the study to document the tribal medicinal practices of the Deb barma clan of the Tripura tribe, which clan can be found residing in Dolusora Tripura Palli of Moulvibazar district of Bangladesh. A further objective was to determine the extent of the community households who still prefer traditional treatment to other forms of treatment, particularly allopathic treatment. METHODS: Interviews of the tribal healer and the tribal community regarding their ethnomedicinal practices were carried out with the help of a semi-structured questionnaire and the guided field-walk method. All together 67 clan members were interviewed including the Headman, tribal healer, 19 Heads of households and 46 other adult members of the clan. Information on number of members of household, their age, gender, educational status, occupation of working household members and preferred mode of treatment was obtained through the semi-structured questionnaire. In the guided field-walk method, the healer took the interviewers on field-walks through areas from where he collected his medicinal plants, pointed out the plants, and described their uses. RESULTS: The clan had a total of 135 people distributed into 20 households and had only one traditional healer. Use of medicinal plants, wearing of amulets, and worship of the evil god 'Bura debta' constituted the traditional medicinal practices of the clan for treatment of diseases. The healer used a total of 44 medicinal plants distributed into 34 families for treatment of various ailments like pain, coughs, cold, gastrointestinal disorders, cuts and wounds, diabetes, malaria, heart disorders, and paralysis. CONCLUSIONS: Available scientific reports validate the use of a number of plants by the traditional healer. A number of the plants used by the clan healer had reported similar uses in Ayurveda, but differ considerably in their therapeutic uses from that reported for other tribes in Bangladesh. The present survey also indicated that in recent years the Deb barma clan members are inclining more towards allopathic medicine.