title: Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.
abstract: OBJECTIVE
  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.
  
  
  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-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ 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.
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: R
authors: R
authors: Kesavan
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: S
authors: S
authors: Chandel
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: S
authors: S
authors: Upadhyay
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: R
authors: R
authors: Bendre
authors: National Institute of Nutrition, Hyderabad, India.
authors: R
authors: R
authors: Ganugula
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: U R
authors: UR
authors: Potunuru
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: H
authors: H
authors: Giri
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: G
authors: G
authors: Sahu
authors: National Institute of Nutrition, Hyderabad, India.
authors: P Uday
authors: PU
authors: Kumar
authors: National Institute of Nutrition, Hyderabad, India.
authors: G Bhanuprakash
authors: GB
authors: Reddy
authors: Department of Physical Chemistry, VINCA Institute of Nuclear Sciences, Belgrade, Serbia.
authors: G
authors: G
authors: Joksic
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
authors: A K
authors: AK
authors: Bera
authors: Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India. Electronic address: mdixit@iitm.ac.in.
authors: Madhulika
authors: M
authors: Dixit
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047310:Apigenin / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000188:drug therapy; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D030012:Gentiana / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000077214:Becaplermin; D047310:Apigenin; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051966:Phospholipase C gamma; C049772:isovitexin
keywords: Atherosclerosis; Endothelial inflammation; Gentiana lutea; Isovitexin; PLC-γ; ROS; Smooth muscle cell