Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals

Abstract Background: The anti-sickling activity of Anogeissus leiocarpus, a plant used for managing sickle cell disease (SCD), has been previously proven. Objectives: This study investigated the anti-sickling mechanism of A. leiocarpus by probing its effects on Gardos channel (KCNN4), erythropo...

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Autores principales:	Taiwo O. Elufioye, Babatunde M. Williams, Mojisola C. Cyril-Olutayo
Formato:	article
Lenguaje:	EN
Publicado:	Hamadan University of Medical Sciences 2020
Materias:	sickle cell anaemia anogeissus leiocarpus gardos channel erythropoiesis mechanism of action Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/83c545b23b1c4bf8a3c2c3b6afee5563
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spelling	oai:doaj.org-article:83c545b23b1c4bf8a3c2c3b6afee55632021-11-20T08:29:17ZIdentification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals10.34172/ajmb.2020.012345-4113https://doaj.org/article/83c545b23b1c4bf8a3c2c3b6afee55632020-06-01T00:00:00Zhttp://ajmb.umsha.ac.ir/PDF/ajmb-8-1.pdfhttps://doaj.org/toc/2345-4113 Abstract Background: The anti-sickling activity of Anogeissus leiocarpus, a plant used for managing sickle cell disease (SCD), has been previously proven. Objectives: This study investigated the anti-sickling mechanism of A. leiocarpus by probing its effects on Gardos channel (KCNN4), erythropoietin (EPO), erythropoietin receptor (EPOR), catalase (CAT), G6pD, D-type cyclins and cyclin-dependent kinase inhibitors (p21) gene expression as well as assessing in silico drug-likeness of reported compounds as EPOR agonist. Methods: A total of 18 rats (45-76 g) were selected and divided into 6 groups (n=3). The control group was given water ad libitum, standard group was given 0.1 mL/kg of Ciklavit® and experimental group was given daily oral doses of 50-100 mg/kg body weight of crude methanol extract or ethyl acetate fraction (EA-PF). Haematological parameters were analyzed while histopathological and molecular studies of kidney and bone marrow were carried out, followed by RT-PCR analysis of KCNN4, EPO, EPOR, CAT, G6pD, p21, and cyclin-dependent kinase inhibitors. Docking studies of the reported compounds were also done. Results: EA-PF had an insignificant (P>0.05) effect on haematological parameters compared to the basal group. While CAT and p21 acted in a positive feedback loop, G6pD was downregulated in the experimental groups. KCNN4 acted in a negative-feedback mechanism and the upregulation of EPO and EPOR was followed by increased reticulocytes. Kaempferol, quercetin, and catechin showed non-violation of Lipinski’s rule and high binding affinities of 6.5 kcal/mol, 6.7 kcal/mol, and 6.7 kcal/mol, respectively, for EPOR pocket compared to the co-crystallized ligand. Conclusion: Results suggest that ethyl acetate fraction of Anogeissus leiocarpus achieved a steady state level of the Gardos channel and stimulation of EPO expression via EPOR agonist. Taiwo O. ElufioyeBabatunde M. WilliamsMojisola C. Cyril-OlutayoHamadan University of Medical Sciencesarticlesickle cell anaemiaanogeissus leiocarpusgardos channelerythropoiesismechanism of actionMedical technologyR855-855.5ENAvicenna Journal of Medical Biochemistry, Vol 8, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	sickle cell anaemia anogeissus leiocarpus gardos channel erythropoiesis mechanism of action Medical technology R855-855.5
spellingShingle	sickle cell anaemia anogeissus leiocarpus gardos channel erythropoiesis mechanism of action Medical technology R855-855.5 Taiwo O. Elufioye Babatunde M. Williams Mojisola C. Cyril-Olutayo Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
description	Abstract Background: The anti-sickling activity of Anogeissus leiocarpus, a plant used for managing sickle cell disease (SCD), has been previously proven. Objectives: This study investigated the anti-sickling mechanism of A. leiocarpus by probing its effects on Gardos channel (KCNN4), erythropoietin (EPO), erythropoietin receptor (EPOR), catalase (CAT), G6pD, D-type cyclins and cyclin-dependent kinase inhibitors (p21) gene expression as well as assessing in silico drug-likeness of reported compounds as EPOR agonist. Methods: A total of 18 rats (45-76 g) were selected and divided into 6 groups (n=3). The control group was given water ad libitum, standard group was given 0.1 mL/kg of Ciklavit® and experimental group was given daily oral doses of 50-100 mg/kg body weight of crude methanol extract or ethyl acetate fraction (EA-PF). Haematological parameters were analyzed while histopathological and molecular studies of kidney and bone marrow were carried out, followed by RT-PCR analysis of KCNN4, EPO, EPOR, CAT, G6pD, p21, and cyclin-dependent kinase inhibitors. Docking studies of the reported compounds were also done. Results: EA-PF had an insignificant (P>0.05) effect on haematological parameters compared to the basal group. While CAT and p21 acted in a positive feedback loop, G6pD was downregulated in the experimental groups. KCNN4 acted in a negative-feedback mechanism and the upregulation of EPO and EPOR was followed by increased reticulocytes. Kaempferol, quercetin, and catechin showed non-violation of Lipinski’s rule and high binding affinities of 6.5 kcal/mol, 6.7 kcal/mol, and 6.7 kcal/mol, respectively, for EPOR pocket compared to the co-crystallized ligand. Conclusion: Results suggest that ethyl acetate fraction of Anogeissus leiocarpus achieved a steady state level of the Gardos channel and stimulation of EPO expression via EPOR agonist.
format	article
author	Taiwo O. Elufioye Babatunde M. Williams Mojisola C. Cyril-Olutayo
author_facet	Taiwo O. Elufioye Babatunde M. Williams Mojisola C. Cyril-Olutayo
author_sort	Taiwo O. Elufioye
title	Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
title_short	Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
title_full	Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
title_fullStr	Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
title_full_unstemmed	Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals
title_sort	identification of the anti-sickling activity of anogeissus leiocarpus and in silico investigation of some of its phytochemicals
publisher	Hamadan University of Medical Sciences
publishDate	2020
url	https://doaj.org/article/83c545b23b1c4bf8a3c2c3b6afee5563
work_keys_str_mv	AT taiwooelufioye identificationoftheantisicklingactivityofanogeissusleiocarpusandinsilicoinvestigationofsomeofitsphytochemicals AT babatundemwilliams identificationoftheantisicklingactivityofanogeissusleiocarpusandinsilicoinvestigationofsomeofitsphytochemicals AT mojisolaccyrilolutayo identificationoftheantisicklingactivityofanogeissusleiocarpusandinsilicoinvestigationofsomeofitsphytochemicals
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Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals

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