Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract: [Figure not available: see fulltext.

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

<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

Antibacterial, Antifungal and Antiviral Activities of Euphorbia Greenwayi var. Greenwayi Bally & S. Carter

The interest in many traditional natural products is increasing. Natural products continue producing bioactive agents owing to the remarkable available chemical diversity. They were evaluated as prospective therapeutic candidates for the treatment of human and animal infectious diseases. Euphorbiaceae, the spurge family, holds a significant place in the domain of plant families, with scientific evidence of antiviral, antibacterial, anticancer, cytotoxic and antitumor properties. In this regard, the current study intends to investigate the antibacterial, antifungal, antiviral and cytotoxic properties of Euphorbia greenwayi var. greenwayi Bally & S. Carter. The dried aerial parts of E. greenwayi var. greenwayi Bally & S. Carter were used, then extracted with 70% ethanol, solvent was distilled off till dryness. The antimicrobial activity of the extract and both MIC and MBC were evaluated against one strain of Gram-positive bacteria: Staphylococcus aureus ATCC9144; four strains of Gram-negative bacteria: Klebsiella pneumonia ATCC10031, Escherichia coli ATCC10536, Salmonella typhi ATCC14028, Pseudomonas aeruginosa ATCC9027and yeast: Candida albicans ATCC10231. The antiviral activity of hydroalcoholic extract against Rotavirus infection was determined as well as the cytotoxic properties. The antibacterial examination revealed potential activity of the hydroalcoholic extract against all tested species with the inhibition zone ranged from 14.7 to 29.7 mm. The highest activity was against S. aureus and C. albicans. MIC and MBC results proved that the extract is potentially bacteriostatic and bactericidal agents against both Gram-positive and Gram-negative bacteria and against the tested yeast. Also, the extract has the ability to prevent Rotavirus attachment with the cell host. This research revealed that the hydroalcoholic extract of aerial parts of E. greenwayi var. greenwayi Bally & S. Carter has significant antimicrobial potential that can be implemented in different pharmaceutical formulations

Immunomodulatory effect of Premna odorata volatile oils in Mycobacterium tuberculosis by inhibiting TLR4/NF-κB pathway

Introduction: The development of multi drug resistant (MDR) tuberculosis (TB) and extensively drug resistant (XDR) TB, increased the interest in the usage of medicinal plants that are complementary to antibiotics to improve anti-TB efficacy. The present study aimed to confirm the anti-TB efficacy of volatile oils (VOs) isolated from different parts of Premna odorata in vivo, and moreover, to test the possible involvement of TLR4/NF-κB signaling pathway in its anti-TB efficacy. Methods: Thirty mice were divided into six equal groups. Group 1: healthy mice (negative control). Groups 2-6 were injected intravenously with a positive TB solution of purified MeDiPro Mycobacterium tuberculosis (MTB) antigen for 7 days to induce tuberculosis. Group 3-6: TB-injected mice treated respectively with leaves VO (300 μL/d), young stems VO (300 μL/d), flowers VO and a combination of the three essential VOs (1:1:1). Various immunologic factors and antioxidant activity were evaluated and compared in the groups. Results: TB-infected mice showed a significant increase in the serum levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukin (IL) 1-β and the mRNA expression levels of toll-like receptor 4 (TLR-4) & nuclear factor-κB (NF-κB) and a decrease in IL-10 & total antioxidant capacity (TAC). While pretreatment with VOs extracted from leaves, flowers, young stems and a combination of the three oils reversed these effects. Conclusion: The immunomodulatory effects of VOs extracted from different parts of P. odorata against TB infection involve the TLR-4/NFκB signaling pathway as well as, antioxidant effects, recommending that the use of this plant may help TB infected patients

Bioassay-guided isolation, metabolic profiling, and docking studies of hyaluronidase inhibitors from Ravenala madagascariensis

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC&ndash;HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care

Attenuation of Smad, Wnt and E2F Signaling by Egyptian Riverhemp Triterpenes in Leukemia Cells

Presenter: Ospanov Meirambekhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1012/thumbnail.jp

Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia

Presenter: Ospanov Meirambekhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1013/thumbnail.jp