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bioRxiv · 10.1101/2021.11.11.468287

Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia.

Adeniyi, O.·Baptista, R.·Bhowmick, S.·Cookson, A. R.·Nash, R.·Winters, A.·Mur, L.
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Abstract

Alchornea cordifolia Mull. 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 >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.

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Adeniyi, O., Baptista, R., Bhowmick, S., Cookson, A. R., Nash, R., Winters, A., Mur, L.. 2021-11-23. Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia.. https://doi.org/10.1101/2021.11.11.468287

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