identification of the anti-sickling activity of anogeissus leiocarpus and in silico investigation of some of its phytochemicals

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 nonviolation 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.