In-silico validation of Traditional Medicines used by tribes of Surguja, Chhattisgarh for the Effective Management of Sickle Cell Disease

Sickle cell disease (SCD) is a severe hereditary blood disorder characterized by abnormal hemoglobin polymerization, leading to distorted, sickle-shaped red blood cells. The primary clinical management of Sickle Cell Disease entails the administration of blood transfusions to maintain the stability of the patient's hemoglobin concentration and the use of hydroxyurea, folic acid, amino acid supplementation, penicillin prophylaxis, and antimalarial prophylaxis. These medications are associated with risk considerations and are highly costly. Ethnic communities of Jashpur district of Chhattisgarh, India practiced traditional medicines such as root extracts of Lygodium japonicum and Trichodesma indicum to treat SCD. This study aimed to screen virtually natural bioactive phytocompounds with anti-sickling properties from these plants. The pharmacokinetic attributes of ten natural compounds from Trichodesma indicum and Lygodium japonicum were screened. Using the AutoDock 4.2 tool, the screened compounds were docked against dimerized human sickle hemoglobin. MD simulations were then utilized to further assess the compounds' binding mode and the complexes' dynamic behavior. Voxelotor (Recently FDA-approved medication for SCD) and Hydroxyurea, a commonly used medication for the treatment of SCD, were employed as standards for comparison. The docking analysis showed binding energies of -2.28 and -6.3 kcal/mol, the lowest and highest, for the mutated HBB-Hydroxyurea and Mutated HBB-Apigenin complexes, respectively. All the phytocomopunds depicted a better binding energy compared to the standard drugs. Apigenin was identified as the most promising candidate for targeting dimerized hemoglobin (Hb) among the eight shortlisted phytochemical compounds, as assessed using virtual docking, RO5 parameters, and pharmacokinetic profiling. According to molecular docking scores, apigenin has a better interaction profile and a higher binding affinity than standard drugs. Molecular dynamics simulations, which showed the structural stability of the apigenin–dimerized Hb complex with minimal conformational changes and sustained intermolecular contacts throughout the simulation period, provided additional support for our findings. All of these findings suggest that apigenin may be a promising treatment option for modulating dimerized hemoglobin.