Alagarsamy Veerachamy, Sulthana Mohaideen Thasthagir, Solomon Viswas Raja, Satishchandra Aithamraju, Kulkarni Vishaka Sumant, Narendhar Bandi, Murugesan Sankaranarayanan, Muzaffar-Ur-Rehman Mohammed, Chandu Ala
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy 502 294, India.
Department of Pharmacy, Birla Institute of Technology & Science, Pilani Campus, Pilani 333 031, India.
Curr Pharm Des. 2025;31(4):307-319. doi: 10.2174/0113816128297758240723104452.
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.
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 molecular docking study.
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.
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.
糖尿病视网膜病变是糖尿病患者视力丧失的主要原因，目前的治疗方法包括使用“超适应症”的糖皮质激素或血管内皮生长因子拮抗剂。多年前就发现了一些针对糖尿病视网膜病变的小分子有机化合物。营养保健品是天然存在的功能性食品，具有多种健康益处，包括维生素、抗氧化剂、矿物质、脂肪酸和氨基酸，它们可以延缓某些疾病的发展。
大量研究报告称，营养保健品具有多种治疗益处，并能预防各种疾病。在糖尿病方面，营养保健品有助于提高胰岛素敏感性、调节新陈代谢并降低高血糖。本研究的主要目的是从天然或植物来源中发现最具活性的药物。在这项工作中，通过分子对接研究，将4种植物中的42种植物化学成分与糖尿病视网膜病变的C4靶点进行了对接。
根据结合能，所有植物成分对靶点都具有良好至高的吸引力，并且6种植物化学成分，如地茶素、石榴皮苷、诃子鞣酸、木麻黄宁、石榴苷和pedunculagin，通过传统氢键、π-烷基相互作用等相互作用，对靶点显示出比标准药物鲁比前列酮更高的结合能。分子动力学模拟研究进一步证实了植物成分的稳定性，而ADMET研究证明了这些植物成分的安全性。
因此，目前的研究表明，各种草药中的植物化学成分可抑制糖尿病视网膜病变的C4靶点，可作为先导化合物开发类似物或重新用于治疗糖尿病视网膜病变。
