PT - JOURNAL ARTICLE AU - Olayemi Adeniyi AU - Rafael Baptista AU - Sumana Bhowmick AU - Alan Cookson AU - Robert Nash AU - Ana Winters AU - Luis A. J. Mur TI - Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from <em>Alchornea cordifolia</em> AID - 10.1101/2021.11.11.468287 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.11.468287 4099 - http://biorxiv.org/content/early/2021/11/23/2021.11.11.468287.short 4100 - http://biorxiv.org/content/early/2021/11/23/2021.11.11.468287.full AB - Alchornea cordifolia Müll. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin [Hb] allele) but the active compounds are yet to be characterised. Herein we describe the use of sequential fractionation coupled with in vitro anti-sickling assays to purify the active component. Sickling was induced in HbSS genotype blood samples using sodium metabisulphite (Na2S2O5) or incubation in 100 % N2. Methanol extracts of A. cordifolia leaves and its sub-fractions showed &gt;70 % suppression of HbSS erythrocyte sickling. Purified compound demonstrated 87.2 ± 2.39 % significant anti-sickling activity and 93.1 ± 2.69 % erythrocyte sickling-inhibition at 0.4 mg/mL. Nuclear magnetic resonance (NMR) spectra and high-resolution mass spectroscopy identified it as quercitrin (quercetin 3-rhamnoside). Purified quercitrin also inhibited the polymerisation of isolated HbS and stabilized sickle erythrocytes membranes. Metabolomic comparisons of blood samples using flow-infusion electrospray-high resolution mass spectrometry indicated that quercitrin could convert HbSS erythrocyte metabolomes to be similar to HbAA. Sickling was associated with changes in anti-oxidants, anaerobic bioenergy and arachidonic acid metabolism, all of which were reversed by quercitrin. The findings described could inform efforts directed to the development of an anti-sickling drug or quality control assessments of A. cordifolia preparations.Competing Interest StatementThe authors have declared no competing interest.