TY  - JOUR
AU  - Kesavan, R.
AU  - Chandel, S.
AU  - Upadhyay, S.
AU  - Bendre, R.
AU  - Ganugula, R.
AU  - Potunuru, U. R.
AU  - Giri, H.
AU  - Sahu, G.
AU  - Kumar, P. Uday
AU  - Reddy, G. Bhanuprakash
AU  - Joksić, Gordana
AU  - Bera, A. K.
AU  - Dixit, Madhulika
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/993
AB  - Background and aims: Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Methods and results: Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-alpha induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-gamma activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Conclusions: Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - Nutrition Metabolism and Cardiovascular Diseases
T1  - Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration
VL  - 26
IS  - 4
SP  - 293
EP  - 301
DO  - 10.1016/j.numecd.2015.12.016
ER  - 

@article{
author = "Kesavan, R. and Chandel, S. and Upadhyay, S. and Bendre, R. and Ganugula, R. and Potunuru, U. R. and Giri, H. and Sahu, G. and Kumar, P. Uday and Reddy, G. Bhanuprakash and Joksić, Gordana and Bera, A. K. and Dixit, Madhulika",
year = "2016",
abstract = "Background and aims: Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Methods and results: Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-alpha induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-gamma activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Conclusions: Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "Nutrition Metabolism and Cardiovascular Diseases",
title = "Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration",
volume = "26",
number = "4",
pages = "293-301",
doi = "10.1016/j.numecd.2015.12.016"
}

Kesavan, R., Chandel, S., Upadhyay, S., Bendre, R., Ganugula, R., Potunuru, U. R., Giri, H., Sahu, G., Kumar, P. U., Reddy, G. B., Joksić, G., Bera, A. K.,& Dixit, M.. (2016). Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration. in Nutrition Metabolism and Cardiovascular Diseases
Elsevier., 26(4), 293-301.
https://doi.org/10.1016/j.numecd.2015.12.016

Kesavan R, Chandel S, Upadhyay S, Bendre R, Ganugula R, Potunuru UR, Giri H, Sahu G, Kumar PU, Reddy GB, Joksić G, Bera AK, Dixit M. Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration. in Nutrition Metabolism and Cardiovascular Diseases. 2016;26(4):293-301.
doi:10.1016/j.numecd.2015.12.016 .

Kesavan, R., Chandel, S., Upadhyay, S., Bendre, R., Ganugula, R., Potunuru, U. R., Giri, H., Sahu, G., Kumar, P. Uday, Reddy, G. Bhanuprakash, Joksić, Gordana, Bera, A. K., Dixit, Madhulika, "Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration" in Nutrition Metabolism and Cardiovascular Diseases, 26, no. 4 (2016):293-301,
https://doi.org/10.1016/j.numecd.2015.12.016 . .

TY  - JOUR
AU  - Kesavan, Rushendhiran
AU  - Potunuru, Uma Rani
AU  - Nastasijević, Branislav J.
AU  - Avaneesh, T.
AU  - Joksić, Gordana
AU  - Dixit, Madhulika
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5430
AB  - Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.
T2  - PLOS One
T1  - Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts
VL  - 8
IS  - 4
DO  - 10.1371/journal.pone.0061393
ER  - 

@article{
author = "Kesavan, Rushendhiran and Potunuru, Uma Rani and Nastasijević, Branislav J. and Avaneesh, T. and Joksić, Gordana and Dixit, Madhulika",
year = "2013",
abstract = "Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.",
journal = "PLOS One",
title = "Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts",
volume = "8",
number = "4",
doi = "10.1371/journal.pone.0061393"
}

Kesavan, R., Potunuru, U. R., Nastasijević, B. J., Avaneesh, T., Joksić, G.,& Dixit, M.. (2013). Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts. in PLOS One, 8(4).
https://doi.org/10.1371/journal.pone.0061393

Kesavan R, Potunuru UR, Nastasijević BJ, Avaneesh T, Joksić G, Dixit M. Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts. in PLOS One. 2013;8(4).
doi:10.1371/journal.pone.0061393 .

Kesavan, Rushendhiran, Potunuru, Uma Rani, Nastasijević, Branislav J., Avaneesh, T., Joksić, Gordana, Dixit, Madhulika, "Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts" in PLOS One, 8, no. 4 (2013),
https://doi.org/10.1371/journal.pone.0061393 . .