Setti A.,Osmania University |
Sankati H.S.,Yogi Vemana University |
Devi T.A.P.,Institute of Bioresources Sustainable Development |
Sekhar A.C.,VAC Biotechnologies |
And 2 more authors.
Journal of Receptors and Signal Transduction | Year: 2013
Primary tumor cells often spread to other organs by metastasis. Despite of it, primary tumor cells break their surrounding extra cellular matrix (ECM) proteins and reach the destination organ by the process of intravasation and extravasation. Metastasized tumor cells induce the process of angiogenesis, this highly regulated process involves several ECM proteins. However, integrins are primarily involved in the blood vessel growth and repair. Therefore, integrins are promising angiogenesis targets. Integrins are receptors on cell surface, involved in signal transduction and attachments in extra cellular matrix (ECM). IntegrinαVβ3 and αVβ5 are implicated in tumor angiogenesis, metastasis, inflammation and bone resorption. The crystal structure of integrinαvβ5 is not available in protein structural databases, therefore; molecular model of integrinβ5 structure was prepared and stereo chemical model quality was checked. Integrin β5 active sites were identified based on insilico analysis tools. Further, molecular level interactions between integrinβ5 and ECM proteins were predicted. In the present study ECM proteins such as focal adhesion kinase 1 (FAK1), annexin A5 and P21 activated kinase 4 (PAK4) were considered for protein-protein docking, to understand inter molecular interactions. The predicted model is conceived to be stereo chemically good and can be used for molecular interaction studies of angiogenic inhibitors. © 2013 Informa Healthcare USA, Inc.
PubMed | Institute of Bioresources & Sustainable Development, Indian Institute of Science and Osmania University
Type: Journal Article | Journal: Journal of receptor and signal transduction research | Year: 2016
Emerging data on cancer suggesting that target-based therapy is promising strategy in cancer treatment. PI3K-AKT pathway is extensively studied in many cancers; several inhibitors target this pathway in different levels. Recent finding on this pathway uncovered the therapeutic applications of PI3K-specific inhibitors; PI3K, AKT, and mTORC broad spectrum inhibitors. Noticeably, class I PI3K isoforms, p110 and p110 catalytic subunits have rational therapeutic application than other isoforms. Therefore, three classes of inhibitors: isoform-specific, dual-specific and broad spectrum were selected for molecular docking and dynamics. First, p110 structure was modelled; active site was analyzed. Then, molecular docking of each class of inhibitors were studied; the docked complexes were further used in 1.2ns molecular dynamics simulation to report the potency of each class of inhibitor. Remarkably, both the studies retained the similar kind of protein ligand interactions. GDC-0941, XL-147 (broad spectrum); TG100-115 (dual-specific); and AS-252424, PIK-294 (isoform-specific) were found to be potential inhibitors of p110 and p110, respectively. In addition to that pharmacokinetic properties are within recommended ranges. Finally, molecular phylogeny revealed that p110 and p110 are evolutionarily divergent; they probably need separate strategies for drug development.
PubMed | Gauhati University and Institute of Bioresources & Sustainable Development
Type: | Journal: Journal of ethnopharmacology | Year: 2016
Parkia roxburghii G. Don. is a traditional medicinal plant and its pods are extensively used as food and medicine. It is believed by the traditional healers to have medicinal properties to treat diabetes, hypertension and urinary tract infections (Jamaluddin et al., 1994).The methanolic extract of pods of P roxburghii and fractions were screened for their -glucosidase and -amylase inhibitory activity. Anti-hyperglycemic effects were studied on streptozotocin (45mg/kg b.w.) induced diabetes in albino rats (seven groups, n=7 n=6), using different doses for 14 days. Plasma glucose concentration (HbA1c) was analysed using whole blood, while SGOT, SGPT, TG, TC and uric acid were analysed using serum, employing commercial kits. Quantitative analysis of the major active constituent was carried out by HPLC-PDA.Bioactivity guided chemical investigation of the edible pods of P roxburghii identified sub-fraction EA-Fr 5 which significantly inhibited -glucosidase (IC50 0.390.06 gmL(-1)), reduced the blood glucose level to normal, and lowered the elevated levels of liver function enzymes SGOT and SGPT in STZ-induced diabetic rats. EA-Fr 5 was found to contain epigallocatechin gallate (1) and hyperin (2) which exhibited significantly higher -glucosidase inhibitory potency with IC50 0.510.09 and 0.710.03M respectively. EA-Fr 5 contained 379.822.90mg/g of EGCG, the major active constituent which manifests a broad spectrum of biological activities.The present investigation for the first time reports the occurrence of EGCG and hyperin in P roxburghii and substantiates the traditional use of pods of P roxburghii as dietary supplement for management of diabetes with significantly promising -glucosidase inhibitory potency and anti-hyperglycemic as well as hepatoprotective effects.
PubMed | Institute of Bioresources & Sustainable Development
Type: | Journal: Journal of ethnopharmacology | Year: 2015
Through one-to-one interaction with the traditional healers, the present study has identified 15 medicinal plant species traditionally used as remedies to control diabetes.The methanolic extracts were screened for their -glucosidase inhibitory activity. Hypoglycemic activity was assessed following glucose, sucrose and starch tolerance test on normal and STZ induced diabetic rats.Ficus cunia extract had the highest -glucosidase inhibitory potency with IC50 1.390.74 g mL(-1) followed by Schima wallichi (IC50 1.430.20 g mL(-1)) and Wendlandia glabrata (IC50 1.670.33 g mL(-1)). In STZ induced diabetic rat model, F. cunia and W glabrata extracts reduced blood glucose concentration to near normal up to 14 days when administered 48 h after STZ.The present study supports the traditional use of some of these medicinal plants in anti-diabetic remedies. The present study contributes to evidence for use of traditional medicine.