Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 8 1 2020 06 29 Identification of the Anti-sickling Activity of Anogeissus leiocarpus and In Silico Investigation of Some of Its Phytochemicals 1 14 10.34172/ajmb.2020.01 EN Taiwo O. Elufioye https://orcid.org/0000-0002-3888-5110 Babatunde M. Williams Mojisola C. Cyril-Olutayo Journal Article 10.34172/ajmb.2020.01 2019 11 15 2020 03 12 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.