Nwankwo, IJP, 2025; Vol. 12(7): 576-588. E- ISSN: 2348-3962, P-ISSN: 2394-5583 International Journal of Pharmacognosy 576 IJP (2025), Vol. 12, Issue 7 (Research Article) Received on 30 June 2025; received in revised form, 29 July 2025; accepted, 30 July 2025; published 31 July 2025 IN-VITRO ANTI-SICKLING POTENTIAL OF CATECHIN AND THE FUNCTIONAL CHEMISTRY AND METABOLIC PATHWAYS ANALYSIS OF HUMAN SICKLE ERYTHROCYTES Henry Chizoba Nwankwo * 1 , Ejike Chukwunyere 1 , Okoro Chukwuemeka Ogbonna 2 , Ume Austine Oraga 3 and Eze Godson Erosbiike 4 Biochemistry Department 1 , Ahmadu Bello University Zaria, Nigeria. Medical Biochemistry Department 2 , David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria. David Umahi Federal University of Health Sciences 3 , Uburu. David Umahi Federal University of Health Sciences 4 , Uburu. ABSTRACT: Sickle cell disease (SCD) treatment and management remain a challenging puzzle, especially among developing Nations. We evaluated catechin‟s sickling-suppressive properties using in-vitro and bioinformatics approaches in human sickle erythrocytes. Sickling was maximally induced (76%) using 2% sodium metabisulfite (SMS) at 3h. Addition of catechin prevented the sickling by SMS at 1mM (81.19%) and reversed the same at 1mM (84.63%), with IC 50 values of 1.026μM and 1.103μM, respectively. Based on functional chemistry, catechin alters the functional groups of certain notable compounds within erythrocytes, favouring its anti-sickling effects, as indicated by the observed bends and shifts. From GC-MS and LC-MS analyses, it was observed that catechin treatment favours fatty acid alkyl monoesters (FAMEs) production with concomitant shutting down effects on selenocompound metabolism. Pathway enrichment and topology analyses revealed activation of fatty acid biosynthesis, linoleic acid metabolism and steroid hormone biosynthesis pathways upon catechin treatment. Thus, sickling-suppressive effects of catechin could potentially be associated with modulation of oxygenated and deoxygenated haemoglobin via alteration of human sickle erythrocytes‟ functional chemistry and metabolic pathways implicated in SCD crisis. INTRODUCTION: Sickle cell disease (SCD) is one of the most prevalent hemoglobinopathies worldwide. It has been hypothesized that this disease originated millions of years ago, in the sub- Saharan countries in mid-western Africa, eastern Asia, and some regions of India. QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.IJP.12(7).576-88 Article can be accessed online on: www.ijpjournal.com DOI link: https://doi.org/10.13040/IJPSR.0975-8232.IJP.12(7).576-88 Today, SCD is not restricted to Africa and parts of India, but is found in the America and Europe, mainly as a result of migration and racial intermingling. In the United States, the disease afflicts approximately 1:500 Afro-American and 1:4000 Hispanic-American neonates 2 . Sickle haemoglobin (HbS) shows peculiar biochemical properties, which lead to it polymerising when deoxygenated. HbS polymerisation is associated with a blood cell membrane deformability and cell-to-cell adherence, adhesion of sickle red blood cells to the endothelium, high production of reactive oxygen Keywords: Sickling, Catechin, Potential, Pathways, Functional chemistry, Metabolomics Correspondence to Author: Henry Chizoba Nwankwo Biochemistry Department, Ahmadu Bello University Zaria, Nigeria. E-mail: henrysilver006@gmail.com