Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration

Maybe we're finally getting down to the real cause of atherosclerosis instead of this pharma focus on cholesterol. But since we don't have a great stroke association we won't get followup research on translating this into an intervention protocol or even the next steps of phase II and III trials. Wait 50 years or never because we have NO stroke strategy or stroke leadership in any part of stroke and this will fall thru the cracks.
http://www.sciencedirect.com/science/article/pii/S0939475315002641

• R. Kesavan^{a, 1},
• S. Chandel^{a, 1},
• S. Upadhyay^{a, 1},
• R. Bendre^a,
• R. Ganugula^b,
• U.R. Potunuru^a,
• H. Giri^a,
• G. Sahu^a,
• U.P. Kumar^b,
• B. Reddy^b,
• G. Joksic^c,
• A.K. Bera^a,
• Dr. M. Dixit^{a, ,}

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doi:10.1016/j.numecd.2015.12.016

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Highlights

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This work highlights the anti-inflammatory and anti-migratory effects of aqueous extract of Gentiana lutea roots, and its constituent isovitexin, on endothelial and smooth muscle cells respectively.

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Isovitexin blocked TNF-α induced expression of adhesion molecules ICAM-1 and VCAM-1 in endothelial cells.

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The extract, as well isovitexin, attenuated PDGF-BB induced ROS/PLC-γ/[Ca²⁺]_i signaling to mediate anti-migratory effects.

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Supplementation of diet with 2% Gentiana lutea extract, blocked atherogenic changes observed in streptozotocin induced diabetic rats.

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Abstract

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. 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 redO 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. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities.

Corresponding author. Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai-600036, India. Tel.: +91 44 22574131; fax: +91 44 22574102.