Shivani Srivastava

Bio: Shivani Srivastava is an academic researcher from Institute of Medical Sciences, Banaras Hindu University. The author has contributed to research in topics: Streptozotocin & Pueraria tuberosa. The author has an hindex of 6, co-authored 24 publications receiving 120 citations. Previous affiliations of Shivani Srivastava include Indian Council of Agricultural Research & Ohio State University.

Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and experimental approach

Abstract: We had earlier reported that the extract of Pueraria tuberosa significantly inhibits DPP-IV enzyme, resulting in glucose tolerance response in rats. In this study, we have explored the active phytochemicals responsible for this potential. The results have been validated in both fasting and postprandial states in the plasma of normal rats and also in fasting blood and intestinal homogenates of diabetic models. Pueraria tuberosa water extract (PTWE) was administered to normal Charles Foster rats for 35 days and to diabetic model (65 mg/kg bw) for 10 days. After treatments, oral glucose tolerance test (OGTT) and insulin was done for 90 min, and the changes in the levels of GLP-1, GIP, and DPP-IV activities were monitored in fasting and postprandial states. In the case of the diabetic model, DPP-IV activity was measured in intestinal homogenate and basal insulin in plasma. The components of PTWE were analyzed via HPLC-MS based on their chemical formula, molecular mass, and retention time. Using the molecular docking study, we have selected the top five components having strong binding energy with DPP-IV. The increase in secretion of GLP-1 and GIP was significantly higher in the postprandial state when compared to fasting condition. GLP-1 plasma concentration increased by 5.8 and 2.9 folds and GIP increased by 8.7 and 2.4 folds in PTWE and control rats, respectively. In contrast, the postprandial decrease in DPP-IV specific activities was recorded at 2.3 and 1.4 folds. The response in OGTT and insulin was also consistent with these changes. In comparison to diabetic controls, PTWE-administered rats showed decreased DPP-IV activity in the intestine, leading to enhanced basal insulin concentration. Through molecular docking, we found Puerarone and Robinin to be the most potential phytochemicals of PTWE for DPP-IV inhibition. Binding energy (kcal/mol) and dissociation constant (pM) of Robinin with DPP-IV protein were found to be 7.543 and 2,957,383.75, respectively. For Puerarone, it was 7.376 and 3,920,309, respectively. Thus, this study provides the novel active components that contribute to the DPP-IV inhibitory property of PTWE.

THE TUBER EXTRACT OF PUERARIA TUBEROSA LINN. COMPETITIVELY INHIBITS DPP-IV ACTIVITY IN NORMOGLYCEMIC RATS Original Article

Abstract: Objective: The main objective of this research was to explore the effect of the polar fraction of tubers of Pueraria tuberosa (PTWE) on DPP-IV activity. Methods: The comparison of in vitro inhibitory potential between commercially available Galvus (Vildagliptin) and PTWE was determined by measuring percent inhibition and IC 50. Results: PTWE has given the IC The enzyme kinetics were also done to reveal the nature of inhibition. In vivo study was done via the glucose tolerance test and by the measurement of increased plasma GLP-1 concentration and DPP-IV activity after glucose load. 50 Conclusion: These findings suggest that antidiabetic effect of PTWE could be because of its role in DPP-IV inhibition. value of 17.4 mg/ml and was found to be a competitive inhibitor having the Ki value of 13.11 mg/ml. Plasma GLP1 concentration was increased and DPP-IV activity was decreased after 60 min of glucose load in PTWE treated rats as compared to control rats. Overall PTWE was found to be less potential DPP-IV inhibitor than Galvus.

The tuber extract of pueraria tuberosa linn. competitively inhibits dpp-iv activity in normoglycemic rats

Abstract: Objective : The main objective of this research was to explore the effect of the polar fraction of tubers of Pueraria tuberosa (PTWE) on DPP-IV activity. Methods : The comparison of in vitro inhibitory potential between commercially available Galvus (Vildagliptin) and PTWE was determined by measuring percent inhibition and IC 50. The enzyme kinetics were also done to reveal the nature of inhibition. In vivo study was done via the glucose tolerance test and by the measurement of increased plasma GLP-1 concentration and DPP-IV activity after glucose load. Results: PTWE has given the IC 50 value of 17.4 mg/ml and was found to be a competitive inhibitor having the Ki value of 13.11 mg/ml. Plasma GLP-1 concentration was increased and DPP-IV activity was decreased after 60 minutes of glucose load in PTWE treated rats as compared to control rats. Overall PTWE was found to be less potential DPP-IV inhibitor than Galvus. Conclusion : These findings suggest that antidiabetic effect of PTWE could be because of its role in DPP-IV inhibition.

Anti-diabetic Phenolic Compounds of Black Carrot (Daucus carota Subspecies sativus var. atrorubens Alef.) Inhibit Enzymes of Glucose Metabolism: An in silico and in vitro Validation.

Abstract: Background Black carrot is known to be effective against Type 2 diabetes. The phenolic compounds present in black carrot are responsible for this property, but limited information was available about the mechanism of action and target enzymes. Objective The present study aims at understanding molecular interactions of phenolic compounds of black carrot with enzymes involved in glucose metabolism in human to identify the potential inhibitor that can be used as candidate drug molecule to control diabetes. Method In vitro assay for inhibition of α-amylase, α-glucosidase and DPP-IV was carried out using black carrot purified extract and the standard inhibitor acarbose and vildagliptin, recpectively. The inhibition activity of selected phenolic compounds was also studied by in silico docking with all these three enzymes for the proper understanding of interactions. Encapsulation of purified black carrot extract was also carried out. Results In vitro IC50 value of purified extract was found to be better than the standard inhibitor acarbose for α-amylase and α-glucosidase, and vildagliptin for DPP-IV. Similarly, docking scores of few anthocyanin molecules were found to be higher than their respective inhibitors, suggesting more effective inhibition. Among anthocyanin molecules of black carrot, cyanidin 3-xylosyl galactoside was found to be the potential drug to inhibit these enzymes, whereas dipeptidyl peptidase IV was identified as the best target to control diabetes with anthocyanins of black carrot. Conclusion Anthocyanins from black carrot were found to be effective to control diabetes and very first time we propose that cyanidin 3-xylosyl galactoside is the best potential molecule for inhibiting enzymes involved in glucose metabolism. The study also shows the encapsulation of anthocyanin compounds using β-cyclodextrin.

Antiproliferation activity and metabolism of black carrot anthocyanins

Abstract: The antiproliferation activity of a black carrot anthocyanin-rich extract (BC-ARE) on human cancer cells (HT-29 colorectal adenocarcinoma and HL-60 promyelocytic leukaemia) and metabolism of its characteristic anthocyanins (acylated and nonacylated forms) in humans were investigated. Cancer cells were exposed for 24 h to 0.0–2.0 mg/mL of BC-ARE. Anthocyanin-rich extract inhibited proliferation of both types of cancer cells in a dose-dependent manner. After ingestion of a black carrot concentrate, three acylated and two nonacylated anthocyanins were excreted in the volunteers (n = 4) urine (0.048% of the administered dose). The anthocyanins were characterized by HPLC-DAD-ESI-MS/MS. Urine recovery of nonacylated anthocyanins was 8-fold higher than that of acylated anthocyanins. Industrial relevance Natural pigments have achieved commercial significance as food colorants due to the fact that consumers perceive them as safe additives. At present extracts rich in acylated anthocyanins, which are known for their outstanding stability, serve as a major source of natural food colours for the food colorant industry with purple sweetpotato, red cabbage and black carrot being the major sources. Beside aesthetic values, anthocyanins possess enhanced physiological activity due to their potent antioxidant properties and enhance the health-promoting qualities of foods. Our findings on cancer cell antiproliferation activity of an anthocyanin-rich black carrot extract as well as information about the bioavailability of black carrot anthocyanins could lead to an increased application of these natural food colorants by the food industry.

DPP-IV Inhibitory Potentials of Flavonol Glycosides Isolated from the Seeds of Lens culinaris: In Vitro and Molecular Docking Analyses

Abstract: Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (1–3) were isolated from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV–inhibitory activity. We demonstrated for the first time, that compounds 1–3 inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds 1–3 within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.