http://www.sciencedirect.com/science/article/pii/S0939475315002641
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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.
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.
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