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

View ORCID ProfileOlayemi Adeniyi, View ORCID ProfileRafael Baptista, View ORCID ProfileSumana Bhowmick, Alan Cookson, View ORCID ProfileRobert Nash, View ORCID ProfileAna Winters, View ORCID ProfileLuis A. J. Mur
doi: https://doi.org/10.1101/2021.11.11.468287
Olayemi Adeniyi
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
2Department of Science Technology: Biochemistry unit, The Federal Polytechnic, Ado – Ekiti, Ekiti State, Nigeria
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Rafael Baptista
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
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Sumana Bhowmick
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
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Alan Cookson
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
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Robert Nash
3PhytoQuest Ltd, Plas Gogerddan, Aberystwyth, Ceredigion SY23 3EB, United Kingdom
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Ana Winters
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
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Luis A. J. Mur
1Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Wales, United Kingdom
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  • For correspondence: lum@aber.ac.uk
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Abstract

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 >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 Statement

The authors have declared no competing interest.

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Posted November 23, 2021.
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Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia
Olayemi Adeniyi, Rafael Baptista, Sumana Bhowmick, Alan Cookson, Robert Nash, Ana Winters, Luis A. J. Mur
bioRxiv 2021.11.11.468287; doi: https://doi.org/10.1101/2021.11.11.468287
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Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia
Olayemi Adeniyi, Rafael Baptista, Sumana Bhowmick, Alan Cookson, Robert Nash, Ana Winters, Luis A. J. Mur
bioRxiv 2021.11.11.468287; doi: https://doi.org/10.1101/2021.11.11.468287

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