Dual Induction of New Microbial Secondary Metabolites by Fungal Bacterial Co-cultivation

We thank the College of Physical Sciences, University of Aberdeen, for provision of infrastructure and facilities in the Marine Biodiscovery Centre. We acknowledge the receipt of funding from the European Union’s Seventh Programme for Research, Technological Development and Demonstration under Grant Agreement No. 312184 (PharmaSea). MR thanks School of Science and Sport, University of the West of Scotland for providing the open-access fees required for the publication.Peer reviewedPublisher PD

Isolation of catechins from Cycas armstrongii Miq. of an Egyptian origin

The phytochemical investigation of Cycas armstrongii Miq. leaves and twigs using different chromatographic techniques led to the isolation of three catechin monomers; catechin (1), epicatechin (2), and epigallocatechin-3-gallate (3), for the first time from this species. The chemotaxonomic significance of the isolated compounds is discussed in the rest of this article

Cecropin A improves the antibacterial activity of hen egg white lysozyme against challenging <i>Salmonella enterica</i> serovars

The prevalence of multidrug-resistant Salmonella enterica among animal- and plant-derived food products threatens global healthcare and economic sectors. Hen egg white lysozyme is widely exploited as a food preservative against Gram-positive pathogens. Nevertheless, its limited penetration of the outer membrane renders it ineffective against Gram-negative bacteria. Herein, we present a safe and effective approach to facilitate HEWL access to peptidoglycan layers using cecropin A. In silico analysis of cecropin A peptide revealed an amphipathic α-helical peptide with potential outer membrane permeabilizing activity through its interaction with both hydrophobic and ionic stabilizing forces. Evaluation of HEWL/cecropin A combination showed a cecropin A dose-dependent bacterial count reduction up to 4.16 and 3.18 ± 0.26 log units against Salmonella enterica ATCC 35664 at the logarithmic and stationary growth phases, respectively. Moreover, the combination displayed antibacterial activity of 2.1 ± 0.31 and ~1 log-unit reductions against Salmonella enterica serovars Kentucky, Typhimurium, and Enteritidis, respectively, whereas Hato and Shangani were found irresponsive. The cytotoxicity assay revealed compatibility of cecropin A with oral epithelial cells. These observations suggest HEWL/cecropin A combination as an effective and safe alternative to lysozyme against Salmonella enterica

CYTOTOXIC AND ANTIOXIDANT ACTIVITIES OF SECONDARY METABOLITES FROM PULICARIA UNDULATA

Objective: To evaluate the in vitro cytotoxicity, antioxidant activities and structure-activity relationship of secondary metabolites isolated from Pulicaria undulata.Methods: The methylene chloride-methanol (1:1) extract of the air-dried aerial parts of Pulicaria undulata was fractionated and separated to obtain the isolated compounds by different chromatographic techniques. Structures of the isolated compounds were determined on the basis of the extensive spectroscopic analysis, including 1D and 2D NMR and compared with the literature data. The crude extract and the isolated compounds were evaluated for in vitro antioxidant activity using the 2,2 diphenyl dipicryl hydrazine (DPPH) method and cytotoxic assay using human breast cancer (MCF-7) and hepatoma (Hep G2) cell line.Results: Nine secondary metabolites were isolated from Pulicaria undulata in this study. Of which two terpenoidal compounds; 8-epi-ivalbin and 11β, 13-dihydro-4H-xanthalongin 4-O-β-D-glucopyranoside firstly isolated from the genus pulicaria and three flavonoids; eupatolitin, 6-methoxykaempferol, and patulitrin firstly isolated from P. undulata. 6-methoxykaempferol (IC50 2.3 µg/ml) showed the most potent antioxidant activity. The highest cytotoxic effect against MCF-7 and Hep G2 cells was obtained with eupatolitin (IC50 27.6 and 23.5 µg/ml) respectively. The structure-activity relationship was also examined and the findings presented here showed that 3, 5, 7, 4' and 3, 5, 4', 5'-hydroxy flavonoids were potent antioxidant and has cytotoxic activity.Conclusion: Pulicaria undulata is a promising medicinal plant, and our study tends to support the therapeutic value of this plant as antioxidant drug and in the treatment of cancer

DNA Fingerprinting, Chemical Composition and Antimicrobial Activity of the Essential Oil isolated from the Fruits of Serenoa repens W. Bartram

The chemical composition of the essential oil obtained from the fruits of Serenoa repens W. Bartram by hydrodistillation has been studied by GC/MS analysis. The analysis of the essential oil revealed the presence of 60 identified compounds (monoterpene and sesquiterpene) oxygenated and non-oxygenated compounds in the oil sample including about 53 compounds which were not reported in GC/MS analysis of the essential oil before. GC/MS analysis revealed 4-(1-methylethyl)-Benzaldehyde to be the major constituent of the essential oil of the fruits 58.56% followed by 2-Caren-10-al and 3-Caren-10-al (11.83% and 2.87%, respectively). So far nothing could be traced concerning the oil biological activity. The antimicrobial sensitivity as well as the MIC against different fungal, gram positive and gram negative strains was carried out. The antimicrobial snsitivity was higher as antifungal followed by the Gram-positive strains, and Gram-negative bacteria strains compared to the positive controls. The essential oil showed high selective antimicrobial potential (MIC 1.95–62.5 μg/mL for bacteria; and MIC 3.9–31.25 μg/mL for fungi). DNA fingerprinting of the cultivated leaves were carried out for authentication of the plant. Keywords: Serenoa repens, essential oil, 4-(1-methylethyl)-Benzaldehyde, Antimicrobial, GC/MS, DNA

Partial synthetic PPARƳ derivative ameliorates aorta injury in experimental diabetic rats mediated by activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR expression

Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPAR&alpha;/&#435; partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 &plusmn; 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPAR&#435; agonist pioglitazone and the partial synthetic PPAR&#435; (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPAR&#435; derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPAR&#435; derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta

<i>Garcinia cambogia</i> phenolics as potent anti-COVID-19 agents:phytochemical profiling, biological activities, and molecular docking

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis, which led to the isolation of eight known compounds. Using spectrometric techniques, the isolated compounds were identified as quercetin, amentoflavone, vitexin, rutin, naringin, catechin, p-coumaric, and gallic acids. The antiviral activities of the isolated compounds were investigated using two assays; the 3CL-Mpro enzyme showed that naringin had a potent effect with IC50 16.62 &mu;g/mL, followed by catechin and gallic acid (IC50 26.2, 30.35 &mu;g/mL, respectively), while the direct antiviral inhibition effect of naringin confirmed the potency with an EC50 of 0.0169 &mu;M. To show the molecular interaction, in situ molecular docking was carried out using a COVID-19 protease enzyme. Both biological effects and docking studies showed the hydrophobic interactions with Gln 189 or Glu 166, per the predicated binding pose of the isolated naringin

Flavonoids as potential anti-MRSA agents through modulation of PBP2a:a computational and experimental study

Recently, the interest in plant-derived antimicrobial agents has increased. However, there are no sufficient studies dealing with their modes of action. Herein, we investigate an in-house library of common plant-based phenolic compounds for their potential antibacterial effects against the methicillin-resistant Staphylococcus aureus (MRSA), a widespread life-threatening superbug. Flavonoids, which are considered major constituents in the plant kingdom, were found to be a promising class of compounds against MRSA, particularly the non-glycosylated ones. On the other hand, the glycosylated derivatives, along with the flavonolignan silibinin A, were able to restore the inhibitory activity of ampicillin against MRSA. To explore the mode of action of this class, they were subjected to an extensive inverse virtual screening (IVS), which suggested penicillin-binding protein 2a (PBP2a) as a possible target that mediates both the antibacterial and the antibiotic-synergistic effects of this class of compounds. Further molecular docking and molecular dynamic simulation experiments were conducted to support the primary IVS and the in vitro results and to study their binding modes with PBP2a. Our findings shed a light on plant-derived natural products, notably flavonoids, as a promising and readily available source for future adjuvant antimicrobial therapy against resistant strains

Nature as a treasure trove of potential anti-SARS-CoV drug leads:a structural/mechanistic rationale

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M(pro)). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future