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Type II Diabetes mellitus (T2DM) and associated complications primarily diabetic retinopathy cases are rising with an alarming rate. Prolong hyperglycemia along with the aldose reductase (AR) activity play a pivotal role in the development of oxidative stress in the aqueous humor and diabetic retinopathy. AR catalyzes conversion of glucose into sorbitol and or fructose get diffuse into lens leading to impaired electrolyte balance and cataract formation. Here in the study, affinity of mangiferin was evaluated first using in silico approaches (Docking studies) and then validated via isothermal titration calorimetry. Here in the present study aim was to check the does mangiferin do have affinity with AR, does mangiferin inhibit the AR and polyol pathway as key pathway involve in the diabetic retinopathy. Both in silico and laboratory investigations were carried out to explore the affinity of mangiferin with the aldose reductase. Swiss target prediction study showed that the AR is prime target of mangiferin in the human proteome. The molecular docking study and affinity searches were performed to seek the bonding pattern and forces involved. Docking (affinity 34.37 kcal/mol) for AR pose 1 was reported superior over the AR pose 2 (affinity -35.46 kcal/mol) against mangiferin. Mangiferin showed significant AR inhibition where IC 50 reported 67.711 µg/ml and highest inhibition was reported at 300 µg/ml i.e. 86.44 %. On the contrary, Quercetin showed much higher inhibition of aldose reductase at similar concentration i.e. 94.47 % at 300 µg/ml with IC 50 59.6014 µg/ml. Here, AR pose 1 showed higher affinity with the mangiferin and confirmed via Isothermal Titration Calorimetry clearly showed higher binding affinity parameters. Binding affinity of AR pose 1 with the mangiferin was higher as showed with affinity parameter determined via ITC i.e. floating association constant (Ka) reported 6.47×10 6 , binding enthalpy (ΔH) -46.11 kJ/mol and higher binding sites (n) i.e. 1.84. Findings demonstrates that the mangiferin is promising AR inhibitor with the ADME prediction (CL R 1.119 ml/min and t 1/2 1.162 h)., Competing Interests: Declaration of Competing Interest Author declare no conflict of Interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Genetic relationships among the ethnic groups are not uniform across the geographical region. Considering this assumption, we analyzed the frequency of the CC-chemokine receptor-5 (CCR5)-∆32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in Bhil tribal and Brahmin caste sample sets from the population., Materials and Methods: 108 blood samples were collected from 6 tribe's populations and a caste population from the district of Vidarbha region., Results and Discussion: The presence of low frequencies of CCR5-Δ32 in an individual of Bhil tribe (0.034, χ(2) value 0.017) in the present study implies that these communities may have a better resistance toward human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) than the other studied tribe sample, as non-show such mutation., Conclusion: The marginal presence of the allele seen in the studied tribal population could be due to gene flow from the people of European descent. However, lack of the homozygous CCR5-Δ32 mutation and the low prevalence of heterozygous CCR5-Δ32 mutations suggest that the Indians are highly susceptible to HIV/AIDS, and this correlates with the highest number of HIV/AIDS infected individuals in India.