The antiproliferative effect of mulberry (Morus alba L.) plant on hepatocarcinoma cell line HepG2

AbstractThis study aimed to investigate the antiproliferative effect of aqueous and organic extracts of mulberry leaves (Morus Alba L.) on human hepatocellular carcinoma HepG2 cell line. Mulberry leaf extracts were prepared using the solvents: water, 50% aqueous MeOH, and 100% MeOH for different time intervals, while the cells treated with dimethyl sulfoxide (DMSO) served as control. The effects of aqueous and organic extracts of M. alba L. leaves on HepG2 cell viability, nuclear factor kappa B (NF-κB) gene expression, alfa-fetoprotein (AFP), albumin (ALB), gamma-glutamyl transpeptidase (γ-GT) and alkaline phosphatase (ALP) were measured. The results of the cell viability assays showed that water, 50% aqueous MeOH, and 100% MeOH extracts exhibited a highly significant inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction in viable cell count. The results were confirmed by microscopical examination of cell morphology. Furthermore, the mulberry leaf extracts suppressed the activity of NF-κB gene expression of HepG2 cells compared to the control. Also a highly significant depression occurred at the levels of AFP, γ-GT and ALP in HepG2 cells compared with that of controls in a time dependent manner. By contrast, the mulberry leaf extracts increased the secretion of ALB. Therefore, the conclusion was that the organic and aqueous extracts of mulberry leaves inhibit the growth of HepG2 cells through suppressing the activity of NF-κB gene expression and modulate the biochemical markers

Renoprotective effect of tectorigenin glycosides isolated from Iris spuria L. (Zeal) against hyperoxaluria and hyperglycemia in NRK-49Fcells

Oxidative stress has been identified as an underlying factor in the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus and it also play major role in kidney stone formation. The present study is aimed to elucidate the in vitro nephroprotective activity of two isoflavonoid glycosides, tectorigenin 7-O-β-D-glucosyl-(1→6)-β-D-glucoside (1) and tectorigenin 7-O-β-D-glucosyl-4'-O-β-D-glucoside (2) isolated from the n-BuOH fraction of Iris spuria L. (Zeal) rhizome MeOH extract against oxalate and high glucose-induced oxidative stress in NRK-49F cells. The results revealed that compounds 1 and 2 significantly increased the antioxidant enzyme activities and decreased MDA levels in both oxalate and high glucose stress. Treatment with these phytochemicals effectively down-regulated expression of crystal modulator genes and pro-fibrotic genes in oxalate and high glucose-mediated stress respectively. This study indicates cytoprotective, antioxidant, anti-urolithic and anti-diabetic effects of compounds 1 and 2 against oxalate and high glucose stress

An Updated Review on the Secondary Metabolites and Biological Activities of Aspergillus ruber and Aspergillus flavus and Exploring the Cytotoxic Potential of Their Isolated Compounds Using Virtual Screening

The secondary metabolites and biological activities of Aspergillus ruber and Aspergillus flavus were comprehensively reported. About 70 compounds were isolated from both species that belong to different classes using conventional and advanced chromatographic techniques and unambiguously elucidated employing one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) and high resolution mass spectrometry (HRMS). Some of them displayed promising antiviral, anti-inflammatory, and antioxidant activities. In silico studies were conducted on human cyclin-dependent kinase 2 (CDK-2), human DNA topoisomerase II (TOP-2), and matrix metalloprotinase 13 (MMP-13) in an effort to explore the cytotoxic potential of the diverse compounds obtained from both Aspergillus species. 1,6,8-Trihydroxy-4-benzoyloxy-3-methylanthraquinone (23) revealed the most firm fitting with the active pockets of CDK-2 and MMP-13; meanwhile, variecolorin H alkaloid (14) showed the highest fitting within TOP-2 with ∆G equals to −36.51 kcal/mole. Thus, fungal metabolites could offer new drug entities for combating cancer. Relevant data about both Aspergillus species up to August 2020 were gathered from various databases comprising Scifinder (https://scifinder.cas.org/scifinder/login) for secondary metabolite-related studies; meanwhile, for biology-related articles, data were collected from both PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) and Web of Knowledge (http://www.webofknowledge.com) as well

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review

Abstract Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them proved a vast array of bioactivity. This review aimed to create an up-to-date comprehensive literature data of A. terreus’s secondary metabolites classes supported by its different bioactivity data to be a scientific record for the next work in drug discovery

A Comprehensive Review of Bioactive Peptides from Marine Fungi and Their Biological Significance

Fungal marine microorganisms are a valuable source of bioactive natural products. Fungal secondary metabolites mainly comprise alkaloids, terpenoids, peptides, polyketides, steroids, and lactones. Proteins and peptides from marine fungi show minimal human toxicity and less adverse effects comparable to synthetic drugs. This review summarizes the chemistry and the biological activities of peptides that were isolated and structurally elucidated from marine fungi. Relevant fungal genera including Acremonium, Ascotricha, Aspergillus, Asteromyces, Ceratodictyon, Clonostachys, Emericella, Exserohilum, Microsporum, Metarrhizium, Penicillium, Scytalidium, Simplicillium, Stachylidium, Talaromyces, Trichoderma, as well as Zygosporium were extensively reviewed. About 131 peptides were reported from these 17 genera and their structures were unambiguously determined using 1D and 2D NMR (one and two dimensional nuclear magnetic resonance) techniques in addition to HRMS (high resolution mass spectrometry). Marfey and Mosher reactions were used to confirm the identity of these compounds. About 53% of the isolated peptides exhibited cytotoxic, antimicrobial, and antiviral activity, meanwhile, few of them showed antidiabetic, lipid lowering, and anti-inflammatory activity. However 47% of the isolated peptides showed no activity with respect to the examined biological activity and thus required further in depth biological assessment. In conclusion, when searching for bioactive natural products, it is worth exploring more peptides of fungal origin and assessing their biological activities

The impact of seasonal variation on the composition of the volatile oil of Polyalthia suberosa (Roxb.) Thwaites leaves and evaluation of its acetylcholinesterase inhibitory activity

Abstract Background Polyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies. Methods The leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure. Results A total of 125 compounds were identified where D-limonene (0.07 − 24.7%), α-copaene (2.25 − 15.49%), E-β-caryophyllene (5.17 − 14.42%), 24-noroleana-3,12-diene (12.92%), β-pinene (0.14 − 8.59%), and α-humulene (2.49–6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme. Conclusions From these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory

Botanicals against some important nematodal diseases: Ascariasis and hookworm infections

Ascariasis and intestinal parasitic nematodes are the leading cause of mass mortality infecting many people across the globe. In light of the various deleterious side effects of modern chemical-based allopathic drugs, our preferences have currently shifted towards the use of traditional plant-based drugs or botanicals for treating diseases. The defensive propensities in the botanicals against parasites have probably evolved during their co-habitation with parasites, humans and plants in nature and hence their combative interference in one another’s defensive mechanisms has occurred naturally ultimately being very effective in treating diseases. This article broadly outlines the utility of plant-based compounds or botanicals prepared from various medicinal herbs that have the potential to be developed as effective therapies against the important parasites causing ascariasis and intestinal hookworm infections leading to ascariasis & infections and thereby human mortality, wherein allopathic treatments are less effective and causes enormous side-effects

Metabolic profiling, antioxidant, and enzyme inhibition potential of Iris pseudacorus L. from Egypt and Japan: A comparative study

Abstract Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC50 values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC50 value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α-glucosidase inhibitory activity displaying IC50 values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC50 value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC50 values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC50 value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals

ISOLATION OF BIOACTIVE COMPOUNDS FROM CENTAUREA AEGYPTIACA

Objective: In a previous study, Centaurea aegyptiaca ethanol and ethyl acetate extracts showed potent cytotoxic effects against laryngeal (HEP2) and hepatic (HEPG2) carcinoma cell lines. Additionally, two novel compounds were isolated and identified. The aim of this study is to continue isolating and identifying another compound (s) that may, also, be responsible for this potent biological activity.Methods: C. aegyptiaca dried aerial parts were extracted with ethanol and ethyl acetate. Both extracts were chromatographed separately to afford seven guaianolides that were identified using different spectroscopic methods. Moreover, compounds 1-7 were evaluated for their cytotoxicity (IC50, µM) against HEP2 and HEPG2 cells in comparison to the normal fibroblasts (BHK) using sulforhodamine B assay. Doxorubicin was used as a positive control.Results: Seven sesquiterpene lactones, centaurepensin, also known as chlorohyssopifolin A (1), 8α-hydroxy-11α, 13-dihydrozaluzanin C (2), chlorohyssopifolin B (3), desacylcynaropicrin (4), chlorohyssopifolin C, acroptilin (5), subluteolide (6), and solstitiolide (7) were isolated from C. aegyptiaca extracts and identified. This is the first report on the occurrence of 2, 4, 5 and 6 in C. aegyptiaca. Compounds 1-4 and 6 exhibited selective cytotoxic effects against HEP2 and HEPG2 cells. However, compounds 1 and 7 showed the highest activities against HEP2 with IC50 values of 10.6±0.02 and 10.9±0.03 µM, respectively. Moreover, compound 3 was the most potent one against HEPG2 cells with IC50value of 13.8±0.05 µM.Conclusions: Chemical investigation of C. aegyptiaca ethanol and ethyl acetate extracts led to the isolation and identification of seven guaianolides. These compounds exhibited good cytotoxic activities against HEP2 and HEPG2 cell lines

Antioxidant Activity of Artocarpus heterophyllus Lam. (Jack Fruit) Leaf Extracts: Remarkable Attenuations of Hyperglycemia and Hyperlipidemia in Streptozotocin-Diabetic Rats

The present study examines the antioxidative, hypoglycemic, and hypolipidemic activities of Artocarpus heterophyllus (jack fruit) leaf extracts (JFEs). The 70% ethanol (JFEE), n-butanol (JFBE), water (JFWE), chloroform (JFCE), and ethyl acetate (JFEAE) extracts were obtained. Both JFEE and JFBE markedly scavenge diphenylpicrylhydrazyl radical and chelate Fe+2in vitro. A compound was isolated from JFBE and identified using 1D and 2D 1H- and 13C-NMR. The administration of JFEE or JFBE to streptozotocin (STZ)-diabetic rats significantly reduced fasting blood glucose (FBG) from 200 to 56 and 79 mg%, respectively; elevated insulin from 10.8 to 19.5 and 15.1 μU/ml, respectively; decreased lipid peroxides from 7.3 to 5.4 and 5.91 nmol/ml, respectively; decreased %glycosylated hemoglobin A1C (%HbA1C) from 6.8 to 4.5 and 5.0%, respectively; and increased total protein content from 2.5 to 6.3 and 5.7 mg%, respectively. Triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), VLDL-C, and LDL/HDL ratio significantly declined by -37, -19, -23, -37, and -39%, respectively, in the case of JFEE; and by -31, -14, -17, -31, and -25%, respectively, in the case of JFBE; as compared to diabetic rats. HDL-C increased by +37% (JFEE) and by +11% (JFBE). Both JFEE and JFBE have shown appreciable results in decreasing FBG, lipid peroxides, %HbA1C, TC, LDL-C, and TG levels, and increasing insulin, HDL-C, and protein content. The spectrometric analysis confirmed that the flavonoid isolated from JFBE was isoquercitrin. We can conclude from this study that JFEE and JFBE exert hypoglycemic and hypolipidemic effects in STZ-diabetic rats through an antioxidative pathway that might be referred to their flavonoid contents