Background Viral and microbial infections constitute one of the most important life-threatening problems. The emergence of new viral and bacterial infectious diseases increases the demand for new therapeutic drugs. Purpose The objective of this study was to use the aqueous and hexane extracts of Lampranthus coccineus and Malephora lutea F. Aizoaceae for the synthesis of silver nanoparticles, and to investigate its possible antiviral activity. In addition to the investigation of the phytochemical composition of the crude methanolic extracts of the two plants through UPLC-MS metabolomic profiling, and it was followed by molecular docking in order to explore the chemical compounds that might contribute to the antiviral potential. Methods The formation of SNPs was further confirmed using a transmission electron microscope (TEM), UV-Visible spectroscopy and Fourier transform infrared spectroscopy. The antiviral activity of the synthesized nanoparticles was evaluated using MTT assay against HSV-1, HAV-10 virus and Coxsackie B4 virus. Metabolomics profiling was performed using UPLC-MS and molecular docking was performed via Autodock4 and visualization was done using the Discovery studio. Results The early signs of SNPs synthesis were detected by a color change from yellow to reddish brown color. The TEM analysis of SNPs showed spherical nanoparticles with mean size ranges between 10.12 nm to 27.89 nm, and 8.91 nm 14.48 nm for Lampranthus coccineus and Malephora lutea aqueous and hexane extracts respectively. The UV-Visible spectrophotometric analysis showed an absorption peak at λmax of 417 nm.The green synthesized SNPs of L. coccineus and M. lutea showed remarkable antiviral activity against HSV-1, HAV-10, and CoxB4 virus. Metabolomics profiling of the methanolic extract of L. coccineus and M. lutea resulted in identifying 12 compounds. The docking study predicted the patterns of interactions between the compounds of L. coccineus and M. lutea with herpes simplex thymidine kinase, hepatitis A 3c proteinase, and Coxsackievirus B4 3c protease, which was similar to those of the co-crystal inhibitors and this can provide a supposed explanation for the antiviral activity of the aqueous and nano extracts of L. coccineus and M. lutea . Conclusion These results highlight that SNPs of L. coccineus and M. lutea could have antiviral activity against HSV-1, HAV-10, and CoxB4 virus.
The green synthesis of silver nanoparticles (SNPs) using plant extracts is an eco-friendly method. It is a single step and offers several advantages such as time reducing, cost-effective and environmental non-toxic. Silver nanoparticles are a type of Noble metal nanoparticles and it has tremendous applications in the field of diagnostics, therapeutics, antimicrobial activity, anticancer and neurodegenerative diseases. In the present work, the aqueous extracts of aerial parts of Lampranthus coccineus and Malephora lutea F. Aizoaceae were successfully used for the synthesis of silver nanoparticles. The formation of silver nanoparticles was early detected by a color change from pale yellow to reddish-brown color and was further confirmed by transmission electron microscope (TEM), UV–visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), and energy-dispersive X-ray diffraction (EDX). The TEM analysis of showed spherical nanoparticles with a mean size between 12.86 nm and 28.19 nm and the UV- visible spectroscopy showed λmax of 417 nm, which confirms the presence of nanoparticles. The neuroprotective potential of SNPs was evaluated by assessing the antioxidant and cholinesterase inhibitory activity. Metabolomic profiling was performed on methanolic extracts of L. coccineus and M. lutea and resulted in the identification of 12 compounds, then docking was performed to investigate the possible interaction between the identified compounds and human acetylcholinesterase, butyrylcholinesterase, and glutathione transferase receptor, which are associated with the progress of Alzheimer’s disease. Overall our SNPs highlighted its promising potential in terms of anticholinesterase and antioxidant activity as plant-based anti-Alzheimer drug and against oxidative stress.
Fungi of the genus Penicillium produce unique and chemically diverse biologically active secondary metabolites, including indole alkaloids. The role of dysregulated hepatocyte growth factor (HGF) and its receptor, c-Met, in the development and progression of breast carcinoma is documented. The goal of this work is to explore the chemistry and bioactivity of the secondary metabolites of the endophytic Penicillium chrysogenum cultured from the leaf of the olive tree Olea europea, collected in its natural habitat in Egypt. This fungal extract showed good inhibitory activities against the proliferation and migration of several human breast cancer lines. The CH2Cl2 extract of P. chrysogenum mycelia was subjected to bioguided chromatographic separation to afford three known indole alkaloids; meleagrin (1), roquefortine C (2) and DHTD (3). Meleagrin inhibited the growth of the human breast cancer cell lines MDA-MB-231, MDA-468, BT-474, SK BR-3, MCF7 and MCF7-dox, while similar treatment doses were found to have no effect on the growth and viability of the non-tumorigenic human mammary epithelial cells MCF10A. Meleagrin also showed excellent ATP competitive c-Met inhibitory activity in Z-Lyte assay, which was further confirmed via molecular docking studies and Western blot analysis. In addition, meleagrin treatment caused a dose-dependent inhibition of HGF-induced cell migration, and invasion of breast cancer cell lines. Meleagrin treatment potently suppressed the invasive triple negative breast tumor cell growth in an orthotopic athymic nude mice model, promoting this unique natural product from hit to a lead rank. The indole alkaloid meleagrin is a novel lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies.
Triple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor. The cell free Z’-LYTE kinase assay, Western blot and in silico docking experiments uncovered, for the first time, c-Met kinase as a potential mechanistic target for rutin-mediated anticancer effects on TNBC cell lines. Likewise, the intraperitoneal injection of rutin at 30 mg/kg, 3X/week, significantly reduced the growth of the TNBC MDA-MB-231/GFP orthotopic xenograft in nude mouse model. These results clearly designate the functional dietary flavonoid rutin as a potential lead for the prevention and control of c-Met-dependent breast malignancies.
Chromatographic separation of aqueous MeOH extract of the leaves of Schinus molle L. has yielded two new acylated quercetin glycosides, named isoquercitrin 6''-O-p-hydroxybenzoate (12) and 2''-O-alpha-L-rhamnopyranosyl-hyperin 6''-O-gallate (13), together with 12 known polyphenolic metabolites for the first time from this species, namely gallic acid (1), methyl gallate (2), chlorogenic acid (3), 2''-alpha-L-rhamnopyranosyl-hyperin (4), quercetin 3-O-beta-D-neohesperidoside (5), miquelianin (6), quercetin 3-O-beta-D-galacturonopyranoside (7), isoquercitrin (8), hyperin (9), isoquercitrin 6''-gallate (10), hyperin 6''-O-gallate (11) and (+)-catechin (14). Their structures were established on the basis of chromatographic properties, chemical, spectroscopic (UV, 1H, 13C NMR) and ESI-MS (positive and negative modes) analyses. Compounds 4-9 and 11 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical and superoxide anion generations with the highest activities shown by 6 and 7 in comparison with that of quercetin as a positive control in vitro.
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