Репозиторий Университета

© 2020 Elsevier B.V. Bioactive compounds from endophytic fungi exhibit diverse biological activities which include anticancer effect. Capitalising on the abundance of unexplored endophytes that reside within marine plants, this study assessed the anticancer potential of ethyl acetate endophytic fungal extracts (i.e. MBFT Tip 2.1, MBL 1.2, MBS 3.2, MKS 3 and MKS 3.1) derived from leaves, stem and fruits of marine plants that grow along Morib Beach, Malaysia. For identification of endophytic fungi, EF 4/ EF 3 and ITS 1/ ITS 4 PCR primer pairs were used to amplify the fungal 18S rDNA sequence and ITS region sequence, respectively. The resultant sequences were subjected to similarity search via the NCBI GenBank database. High-performance thin layer chromatography (HPTLC) hyphenated with bioassays was used to characterise the extracts in terms of their phytochemical profiles and bioactivity. Microchemical derivatisation was used to assess polyphenolic and phytosterol/ terpenoid content whereas biochemical derivatisation was used to establish antioxidant activities and α-amylase enzyme inhibition. The sulforhodamine B (SRB) assay was used to assess the anticancer effect of the extracts against HCT116 (a human colorectal cancer cell line). The present results indicated MBS 3.2 (Penicillium decumbens) as the most potent extract against HCT116 (IC50 = 0.16 μg/mL), approximately 3-times more potent than 5-flurouracil (IC50 = 0.46 μg/mL). Stepwise multiple regression method suggests that the anticancer effect of MBS 3.2 could be associated with high polyphenolic content and antioxidant potential. Nonlinear regression analysis confirmed that low to moderate α-amylase inhibition exhibits maximum anticancer activity. Current findings warrant further in-depth mechanistic studies.

© 2018 Fedoros et al. Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.

© 2018 Nutritec. All Rights Reserved.  The aim of this study was to examine the effect of polyphenol quercetin on morphological changes in nonalcoholic fatty liver disease (NAFLD) in rats fed high-fructose diet. Material and methods. For 20 weeks animals (n=8 in each group) of the 1 st group were given standard diet and water; the 2 nd group - standard diet and 20% fructose solution; the 3 rd group - standard diet with quercetin supplementation (0.1%) and 20% fructose solution. Formalin-fixed and paraffin-embedded liver samples were sectioned, stained (hematoxilin and eosin, Van Gieson's stain), evaluated with the use of the SAF and NAS scales. Results and discussion. Histological assessment did not reveal pathology in the structure of the liver of the 1 st group rats (SOAOFO; NAS - 0, fibrosis - 0). The 2 nd group rat livers disclosed micro-, mid- and macrovesicular steatosis, inflammation without ballooning, pericellular and periportal fibrosis (S2A1F2; NAS - 3, fibrosis - 2). Quercetin-treated rats exhibited in liver significantly less steatosis without significant changes in inflammation and fibrosis features (S1A1F2; NAS - 2, fibrosis - 2) compared with rats of the 2 nd group. Conclusion. The data obtained demonstrate the ability of quercetin to inhibit the development of NAFLD in rats fed a diet with a high content of fructose, by reducing the severity of hepatostatosis.