A dipyrrole derivative from Aloe vera inhibits an anti-diabetic drug target Dipeptidyl Peptidase (DPP)-IV in vitro.
TL;DR: The results of the studies suggested that the inhibition of the DPP-IV enzyme as one of the pathways by which the Aloe vera extract may restore the pancreatic islets cell mass in diabetic animal model.
Abstract: Aloe vera, a succulent herb, has a long history of use in traditional medicine, including diabetes. Earlier studies from our laboratory demonstrated that the Aloe vera extract has the ability to inhibit the diabetic drug target dipeptidyl peptidase (DPP) IV in vitro. This current study focuses on the isolation of small water soluble active molecule(s) involved in DPP-IV inhibition from Aloe vera extract, and further to characterize its structure and to elucidate the mode of inhibition of the DPP-IV enzyme. Aloe vera gel ethanolic extract was subjected to preparative reverse-phase high-pressure liquid chromatography (RP-HPLC), LH-20 Sephadex gel filtration chromatography, followed by analytical RP-HPLC, to isolate the active molecule involved in DPP-IV inhibition. Based on the spectroscopic studies, the structure of the isolated DPP-IV inhibitor was predicted to be 3, 6-dioxo-3, 3a, 6, 6 a-tetrahydropyrrolo [3, 4-c] pyrrole-1, 4-dicarboxamide with the chemical formula C8H6N4O4, having the molecular weight of 225.175 Da. This molecule inhibited the DPP-IV enzyme in a noncompetitive manner with an IC50 value of 8.59 ± 2.61 µM, with a Ki of 4.7 ± 0.038 µM. Thus, the mechanism of DPP-IV inhibition and the inhibitory constants were determined. The results of our studies suggested that the inhibition of the DPP-IV enzyme as one of the pathways by which the Aloe vera extract may restore the pancreatic islets cell mass in diabetic animal model.
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TL;DR: In this article, the authors employed an in-silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.
23 citations
TL;DR: In this article, a review of DPP-IV inhibitors and their mechanism of inhibition, activities of those isolated from various natural sources, and their capacity to overcome oxidative stress in disease conditions is presented.
Abstract: Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia that is predominantly caused by insulin resistance or impaired insulin secretion, along with disturbances in carbohydrate, fat and protein metabolism. Various therapeutic approaches have been used to treat diabetes, including improvement of insulin sensitivity, inhibition of gluconeogenesis, and decreasing glucose absorption from the intestines. Recently, a novel approach has emerged using dipeptidyl peptidase-IV (DPP-IV) inhibitors as a possible agent for the treatment of T2DM without producing any side effects, such as hypoglycemia and exhaustion of pancreatic β-cells. DPP-IV inhibitors improve hyperglycemic conditions by stabilizing the postprandial level of gut hormones such as glucagon-like peptide-1, and glucose-dependent insulinotropic polypeptides, which function as incretins to help upregulate insulin secretion and β-cell mass. In this review, we summarized DPP-IV inhibitors and their mechanism of inhibition, activities of those isolated from various natural sources, and their capacity to overcome oxidative stress in disease conditions.
21 citations
TL;DR: In this article, the authors investigated the simultaneous effect of ethanolic A. vera gel extract on diabetes and obesogenic milieu in Streptozotocin-induced WNIN/GR-Ob mutant obese rats.
12 citations
TL;DR: The output of this research bestows support to utilize the SCKP stirred batch extract as a promising source of antioxidant and antidiabetic compounds in ayurvedic formulations.
Abstract: Syzygium cumini, owing to higher bioactive constituents, its parts principally kernels are used for the antidiabetic purpose since the olden days. The current manuscript illustrated batch extraction of phenolic compounds from S. cumini using a stirred extractor. The yields 0.61 mg/g, 35.9 mg/g, 79.89 mg GAE/g, and 7.29 mg CE/g of catechin, gallic acid, TPC and TFC, respectively, were obtained in 105 min. at 1:20 SCKP to water, 50 ± 2 °C temperature, 4 pH, at 250 rpm and 106 µm particle size of SCKP. In vitro evaluation of the antioxidant and antidiabetic potential of the obtained aqueous extract was carried out by DPPH, α-amylase, and α-glucosidase inhibitory assays. The IC50 values of SCKP aqueous extract obtained were 12.97, 9.03, and 7.13 µg/mL for DPPH scavenging, inhibition of α-amylase, and α-glucosidase, respectively. The cost required to extract 1 kg of catechin, gallic acid, TPC, and TFC was Rs 6691.6, 113.7, 51.1, and 559.93/-, respectively. Stirred batch extraction technique manifests traditional but simple, ecofriendly, and efficient compared to other traditional techniques. The output of this research bestows support to utilize the SCKP stirred batch extract as a promising source of antioxidant and antidiabetic compounds in ayurvedic formulations.
7 citations
TL;DR: In this paper, the authors evaluated the effect of piperine on Alzheimer's disease in diabetic rats and showed that piperines not only improved memory but also reduced the expression of specific AD-related genes.
Abstract: There is accumulating evidence showing that hyperglycemia conditions like diabetes possess a greater risk of impairment to the neuronal system because high glucose levels exacerbate oxidative stress, accumulation of amyloid-beta peptides, and mitochondrial dysfunction, and impair cognitive functions and cause neurodegeneration conditions like Alzheimer's diseases. Due to the extensive focus on pharmacological intervention to prevent neuronal cells' impairment induced by hyperglycemia, the underlying molecular mechanism that links between Diabetes and Alzheimer's is still lacking. Given this, the present study aimed to evaluate the protective effect of piperine on streptozotocin (STZ) induced hyperglycemia and candidate gene expression. In the present study, rats were divided into four groups: control (Vehicle only), diabetic control (STZ only), piperine treated (20 mg/kg day, i.p), and sitagliptin (Positive control) treated. The memory function was assessed by Morris water maze and probe test. After treatment, biochemical parameters such as HOMA index and lipid profile were estimated in the serum, whereas histopathology was evaluated in pancreatic and brain tissue samples. Gene expression studies were done by real-time PCR technique. Present data indicated that piperine caused significant memory improvement as compared to diabetic (STZ) control. The assessment of HOMA indices in serum samples showed that piperine and sitagliptin (positive control, PC) caused significant alterations of insulin resistance, β cell function, and insulin sensitivity. Assessment of brain and pancreas histopathology shows significant improvement in tissue architecture in piperine and sitagliptin treated groups compared to diabetic control. The gene expression profile in brain tissue shows significantly reduced BACE1, PSEN1, APAF1, CASPASE3, and CATALASE genes in the piperine and sitagliptin (PC) treated groups compared to Diabetic (STZ) control. The present study demonstrated that piperine not only improves memory in diabetic rats but also reduces the expression of specific AD-related genes that can help design a novel strategy for therapeutic intervention at the molecular level.
7 citations
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TL;DR: In this article, the authors evaluated DPP-IV inhibitory activities vis a vis anti-peroxidative potential, if any, in two antidiabetic plants, W. somnifera (WS) root and T. foenum-graecum (TFG) seeds.
Abstract: The incretin hormone glucagon-like peptide 1 (GLP-1), proposed as a new target for the treatment of type 2 diabetes, is rapidly cleaved by dipeptidyl peptidase-IV enzyme (DPP-IV/CD26). DPP-IV inhibitors enhance circulating GLP-1 level, which in turn resulted into improved glucose tolerance and insulin secretion. The present study was designed to evaluate DPP-IV inhibitory activities vis a vis anti-peroxidative potential, if any, in two antidiabetic plants. We studied in vitro DPP-IV inhibition; DPPH radical scavenging potential; s-carotene bleaching; reducing power and total phenolics content at the varying concentrations (0.1 – 1 mg/ml) in the extracts of W. somnifera (WS) root and T. foenum-graecum (TFG) seeds. Methanolic extract (0.5 mg/ml) of WS inhibited DPP-IV activities (69.7 ±0.56%) at greater extent than that of TFG (51.8±1.24%), as compared to control. WS extract contains relatively higher amount of total phenolics, elevated DPPH free radical scavenging potential and pronounced reducing power efficacy than that of TFG. The result of present study ravel that WS and TFG extracts contain some novel DPP-IV inhibitors with antiperoxidative potential and could be developed as therapeutic molecules for type 2 diabetes mellitus.
6 citations
"A dipyrrole derivative from Aloe ve..." refers background in this paper
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Journal Article•
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