Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy

Abstract

Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBEDB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

“…CYP450 and isoforms are detoxifying enzymes central to drug metabolism, and inhibition of these enzymes can lead to toxicity. 22,23 Despite the in silico predicted hepatotoxicity, no RA-5 (at 100 μM) cytotoxicity was observed in HepG2 cells.…”

Identification of Potential Molecular Targets and Active Ingredients of Mingmu Dihuang Pill for the Treatment of Diabetic Retinopathy Based on Network Pharmacology

“…The grid box size was set using the software AutoDock Vina version 1.5.6, and the docking results were visualized using the PyMOL software [ 21 ]. A negative binding energy indicates a high likelihood of the binding between the ligand and receptor [ 15 , 22 , 23 ].…”

“…The grid box size was set using the software AutoDock Vina version 1.5.6, and the docking results were visualized using the PyMOL software [21]. A negative binding energy indicates a high likelihood of the binding between the ligand and receptor [15,22,23]. officinalis, 2 active ingredients of A. sinensis, 13 active ingredients of P. lactiflora, 12 active ingredients of T. terrestris, and 4 active ingredients of C. haliotidis.…”

“…Previous studies have demonstrated that Mingmu Dihuang pills are effective to reduce the area of ecchymosis and number of retinal microangioma and to improve the vision sight among patients with diabetic retinopathy [10][11][12][13][14]. However, the targets and active ingredients of Mingmu Dihuang pill for the treatment of diabetic retinopathy have not been fully understood until now [15].…”

Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis Based on GC‐MS, Network Pharmacology, and Molecular Docking

“…Recently, network pharmacology has been successfully employed to investigate the active compounds and the underlying mechanism of TCM with complex chemical composition [26][27][28][29][30]. Molecular docking simulation is an important way of drug virtual screening, which can provide useful information about drug-receptor interactions by calculating the binding energy of small-molecule ligands (drugs) with proteins (receptors) [31][32][33][34][35]. Recently, molecular docking simulation has been widely used to explore the mechanism of TCM [36][37][38][39][40].…”