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INTRODUCTION: Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the current treatment involves the practice of glucocorticoids or VEGF antagonists that are "off-label". A few small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids, and amino acids that can defer the development of some diseases. METHODS: Numerous studies reported that nutraceuticals encourage multiple therapeutic benefits and provide protection against various diseases. In diabetes, nutraceuticals contribute to improving insulin sensitivity, metabolism regulation, and lower hyperglycemia. The major aim of this study is to discover the most active drug from natural or plant sources. In this work, 42 phytochemical constituents from 4 kinds of plants were docked with the C4 target of diabetic retinopathy by an in silico molecular docking study. RESULTS: According to the binding energy, all the phytoconstituents possessed good to high attraction towards the target, and 6 phytochemicals, such as terchebulin, punicalagin, chebulagic acid, casuarinin, punicalin, and pedunculagin, disclosed superior binding energy towards the target than standard ruboxistaurin via the interactions of conventional hydrogen bonding, pi-alkyl interactions, etc. Molecular dynamic simulation studies further established the stability of the phytoconstituents, and ADMET studies proved the safety profile of these phytoconstituents. CONCLUSION: Hence, the current study suggested that the phytochemicals from various herbs inhibit the C4 target of diabetic retinopathy and can be utilized as lead compounds to develop analogs or repurposed for the treatment of DR.
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OBJECTIVE: The peculiar aim of this study is to discover and identify the most effective and potential inhibitors against the most influential target ERα receptor by in silico studies of 45 phytochemicals from six diverse ayurvedic medicinal plants. METHODS: The molecular docking investigation was carried out by the genetic algorithm program of AutoDock Vina. The molecular dynamic (MD) simulation investigations were conducted using the Desmond tool of Schrödinger molecular modelling. This study identified the top ten highest binding energy phytochemicals that were taken for drug-likeness test and ADMET profile prediction with the help of the web-based server QikpropADME. RESULTS: Molecular docking study revealed that ellagic acid (-9.3 kcal/mol), emodin (-9.1 kcal/mol), rhein (-9.1 kcal/mol), andquercetin (-9.0 kcal/mol) phytochemicals showed similar binding affinity as standard tamoxifen towards the target protein ERα. MD studies showed that all four compounds possess comparatively stable ligand-protein complexes with ERα target compared to the tamoxifen-ERα complex. Among the four compounds, phytochemical rhein formed a more stable complex than standard tamoxifen. ADMET studies for the top ten highest binding energy phytochemicals showed a better safety profile. CONCLUSION: Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for treating breast cancer, according to the notion of drug repurposing. Hence, these phytochemicals can be further studied and used as a parent core molecule to develop innovative lead molecules for breast cancer therapy.