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      Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable

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          Abstract

          Background

          The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative.

          Aim

          This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts.

          Methods

          The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques.

          Results

          The total crude extract showed good antiplasmodial activity (IC 50 = 11.890  µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC 50 values of 6.217 and 6.285  µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract.

          Conclusion

          The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.

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          Most cited references76

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          The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay.

          A simple, automated test measuring the ferric reducing ability of plasma, the FRAP assay, is presented as a novel method for assessing "antioxidant power." Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. Measured stoichiometric factors of Trolox, alpha-tocopherol, ascorbic acid, and uric acid are all 2.0; that of bilirubin is 4.0. Activity of albumin is very low. Within- and between-run CVs are <1.0 and <3.0%, respectively, at 100-1000 micromol/liter. FRAP values of fresh plasma of healthy Chinese adults: 612-1634 micromol/liter (mean, 1017; SD, 206; n = 141). The FRAP assay is inexpensive, reagents are simple to prepare, results are highly reproducible, and the procedure is straightforward and speedy. The FRAP assay offers a putative index of antioxidant, or reducing, potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects.
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            Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E.

            A spectrophotometric method has been developed for the quantitative determination of antioxidant capacity. The assay is based on the reduction of Mo(VI) to Mo(V) by the sample analyte and the subsequent formation of a green phosphate/Mo(V) complex at acidic pH. The method has been optimized and characterized with respect to linearity interval, repetitivity and reproducibility, and molar absorption coefficients for the quantitation of several antioxidants, including vitamin E. The phosphomolybdenum method, in combination with hexane monophasic extraction, has also been adapted for the specific determination of vitamin E in seeds. The results obtained with the proposed method were validated by comparison with a standard HPLC method. The phosphomolybdenum method is routinely applied in our laboratory to evaluate the total antioxidant capacity of plant extracts and to determine vitamin E in a variety of grains and seeds, including corn and soybean. Copyright 1999 Academic Press.
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              Artemisinin resistance in Plasmodium falciparum malaria.

              Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance. We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.) 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                Journal
                Adv Pharmacol Pharm Sci
                Adv Pharmacol Pharm Sci
                aps
                Advances in Pharmacological and Pharmaceutical Sciences
                Hindawi
                2633-4682
                2633-4690
                2024
                9 January 2024
                : 2024
                : 4541581
                Affiliations
                1Department of Biomedical Sciences, School of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana
                2Small Animal Teaching Hospital, SVM, CBAS, University of Ghana, Legon, Accra, Ghana
                3Department of Pharmacotherapeutics and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana
                4Department of Chemistry, School of Physical Sciences, University of Cape Coast, Cape Coast, Ghana
                5Department of Epidemiology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
                6Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
                7Department of Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana
                Author notes

                Academic Editor: Farshad Mirzavi

                Author information
                https://orcid.org/0000-0002-8317-9602
                https://orcid.org/0000-0001-6560-1147
                https://orcid.org/0000-0003-3451-4379
                https://orcid.org/0000-0002-4341-3361
                Article
                10.1155/2024/4541581
                10791479
                38235482
                10eb1dca-c643-4049-80c8-7ae373777e17
                Copyright © 2024 Mustapha A. Ahmed et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 August 2023
                : 19 December 2023
                : 23 December 2023
                Funding
                Funded by: University of Cape Coast
                Funded by: University of Cape Coast's Directorate of Research, Innovation, and Consultancy (DRIC)
                Categories
                Research Article

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