Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase
Background: African trypanosomiasis is a protozoan disease with huge socio-economic burden to sub-Saharan African exceeding US$4.6 annual loss. To mitigate the incidence of trypanosomal drug resistance, efforts are geared towards discovery of molecules, especially from natural products, with potenti...
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Elsevier
2022-05-01
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Series: | Phytomedicine Plus |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031322000094 |
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author | Abdullah M. Tauheed Mohammed Mamman Abubakar Ahmed Mohammed M. Suleiman Emmanuel O. Balogun |
author_facet | Abdullah M. Tauheed Mohammed Mamman Abubakar Ahmed Mohammed M. Suleiman Emmanuel O. Balogun |
author_sort | Abdullah M. Tauheed |
collection | DOAJ |
description | Background: African trypanosomiasis is a protozoan disease with huge socio-economic burden to sub-Saharan African exceeding US$4.6 annual loss. To mitigate the incidence of trypanosomal drug resistance, efforts are geared towards discovery of molecules, especially from natural products, with potential to inhibit important molecular target (trypanosome alternative oxidase, TAO) in trypanosomes that are critical to their survival. Method: Crude methanol extract of Anogeissus leiocarpa was subjected to in vitro bioassay-guided antitrypanosomal assay to identify the most active extract with trypanocidal activity. The most active extract was run on a column chromatography yielding five fractions, F1-F5. The fractions were assayed for inhibitory effect on TAO. The most promising TAO inhibitor was subjected to antitrypanosomal evaluation by trypanosome count, drug incubation infectivity test (DIIT) and in vivo studies. Gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify phytochemical constituents of the potential TAO-inhibiting fraction. Results: Ethyl acetate extract (EtOAc) significantly (p<0.05) produced trypanocidal effect and was the most active extract. Of the five fractions, only F4 significantly (p<0.05) inhibited TAO compared to the control. F4 completely immobilised the trypanosomes up to 0.5 µg/µl, yielding an EC50 of 0.024 µg/µl compared to the 0.502 µg/µl of diminazene aceturate positive control group. The DIIT showed that F4 was significantly (p<0.05) potent up to 0.1 µg/µl. F4 significantly (p<0.05) suppressed parasite multiplication in systemic circulation of the treated rats and significantly (p<0.05) maintained high PCV when compared to the 5% DMSO group. Furthermore, F4 significantly (p<0.05) lowered serum concentrations of malondialdehyde. Phytoconstituents identified by the GC-MS include tetradecene; cetene; 3-(benzylthio) acrylic acid, methyl ester; 1-octadecene; 9-heptadecanone; hexadecanoic acid, methyl ester; dibutyl phthalate; eicosene; octadecenoic acid, methyl ester; oleic acid; 2-methyl-Z,Z-3,13-octadecadienol; 1-docosene; 3-phenylthiane, s-oxide; phenol, 3-methyl; phthalic acid, di(2-propylpentyl) ester and 1,4-benzenedicarboxylic acid, bis (2-ethylhexyl) ester. Conclusion: F4 from EtOAc contains six carbohydrates (9.58%), two free fatty acids (6.48%), five fatty acid esters (27.73%), two aromatic compounds (50.63%) and one organosulphide (5.61%). It inhibited TAO and demonstrated antitrypanosomal effects. |
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spelling | doaj.art-94d9506ef3bc419680d68772f155381f2022-12-22T02:53:54ZengElsevierPhytomedicine Plus2667-03132022-05-0122100223Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidaseAbdullah M. Tauheed0Mohammed Mamman1Abubakar Ahmed2Mohammed M. Suleiman3Emmanuel O. Balogun4Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, Nigeria; Corresponding author.Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, NigeriaDepartment of Pharmacognosy and Drug Development, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, NigeriaDepartment of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna State, NigeriaDepartment of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria; Africa Centre of Excellence for Neglected Tropical Diseases and Forensic Biotechnology (ACENTDFB), Ahmadu Bello University, Zaria, NigeriaBackground: African trypanosomiasis is a protozoan disease with huge socio-economic burden to sub-Saharan African exceeding US$4.6 annual loss. To mitigate the incidence of trypanosomal drug resistance, efforts are geared towards discovery of molecules, especially from natural products, with potential to inhibit important molecular target (trypanosome alternative oxidase, TAO) in trypanosomes that are critical to their survival. Method: Crude methanol extract of Anogeissus leiocarpa was subjected to in vitro bioassay-guided antitrypanosomal assay to identify the most active extract with trypanocidal activity. The most active extract was run on a column chromatography yielding five fractions, F1-F5. The fractions were assayed for inhibitory effect on TAO. The most promising TAO inhibitor was subjected to antitrypanosomal evaluation by trypanosome count, drug incubation infectivity test (DIIT) and in vivo studies. Gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify phytochemical constituents of the potential TAO-inhibiting fraction. Results: Ethyl acetate extract (EtOAc) significantly (p<0.05) produced trypanocidal effect and was the most active extract. Of the five fractions, only F4 significantly (p<0.05) inhibited TAO compared to the control. F4 completely immobilised the trypanosomes up to 0.5 µg/µl, yielding an EC50 of 0.024 µg/µl compared to the 0.502 µg/µl of diminazene aceturate positive control group. The DIIT showed that F4 was significantly (p<0.05) potent up to 0.1 µg/µl. F4 significantly (p<0.05) suppressed parasite multiplication in systemic circulation of the treated rats and significantly (p<0.05) maintained high PCV when compared to the 5% DMSO group. Furthermore, F4 significantly (p<0.05) lowered serum concentrations of malondialdehyde. Phytoconstituents identified by the GC-MS include tetradecene; cetene; 3-(benzylthio) acrylic acid, methyl ester; 1-octadecene; 9-heptadecanone; hexadecanoic acid, methyl ester; dibutyl phthalate; eicosene; octadecenoic acid, methyl ester; oleic acid; 2-methyl-Z,Z-3,13-octadecadienol; 1-docosene; 3-phenylthiane, s-oxide; phenol, 3-methyl; phthalic acid, di(2-propylpentyl) ester and 1,4-benzenedicarboxylic acid, bis (2-ethylhexyl) ester. Conclusion: F4 from EtOAc contains six carbohydrates (9.58%), two free fatty acids (6.48%), five fatty acid esters (27.73%), two aromatic compounds (50.63%) and one organosulphide (5.61%). It inhibited TAO and demonstrated antitrypanosomal effects.http://www.sciencedirect.com/science/article/pii/S2667031322000094Anaemia ameliorationDrug discoveryEnzyme inhibition assayMedicinal plantTarget-based screeningTrypanosoma congolense |
spellingShingle | Abdullah M. Tauheed Mohammed Mamman Abubakar Ahmed Mohammed M. Suleiman Emmanuel O. Balogun Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase Phytomedicine Plus Anaemia amelioration Drug discovery Enzyme inhibition assay Medicinal plant Target-based screening Trypanosoma congolense |
title | Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
title_full | Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
title_fullStr | Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
title_full_unstemmed | Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
title_short | Antitrypanosomal properties of Anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
title_sort | antitrypanosomal properties of anogeissus leiocarpa extracts and their inhibitory effect on trypanosome alternative oxidase |
topic | Anaemia amelioration Drug discovery Enzyme inhibition assay Medicinal plant Target-based screening Trypanosoma congolense |
url | http://www.sciencedirect.com/science/article/pii/S2667031322000094 |
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