Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration
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2016
Authors
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
Article (Published version)
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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 demon...strated 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.
Keywords:
Atherosclerosis / Gentiana lutea / Isovitexin / Endothelial inflammation / Smooth muscle cell / PLC-gamma / ROSSource:
Nutrition Metabolism and Cardiovascular Diseases, 2016, 26, 4, 293-301Publisher:
- Elsevier
Funding / projects:
- Department of Biotechnology, Government of India [BT/IN/EU/17/SN/2009]], Council for Scientific and Industrial Research (CSIR), Government of India [CSIR-SRA (13-8553A) 2012/POOL]
DOI: 10.1016/j.numecd.2015.12.016
ISSN: 0939-4753; 1590-3729
PubMed: 26868432
WoS: 000373525600003
Scopus: 2-s2.0-84956957810
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VinčaTY - 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 . .