R Kesavan1, S Chandel1, S Upadhyay1, R Bendre1, R Ganugula2, U R Potunuru1, H Giri1, G Sahu1, P Uday Kumar2, G Bhanuprakash Reddy2, G Joksic3, A K Bera1, Madhulika Dixit4. 1. Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India. 2. National Institute of Nutrition, Hyderabad, India. 3. Department of Physical Chemistry, VINCA Institute of Nuclear Sciences, Belgrade, Serbia. 4. 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.
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-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.
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 diabeticrats. 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-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 STZrats, 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 diabeticrats 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 diabeticrats following GL treatment. CONCLUSIONS: Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities.
Authors: Mona Hoseini Soflaee; Rushendhiran Kesavan; Umakant Sahu; Alpaslan Tasdogan; Elodie Villa; Zied Djabari; Feng Cai; Diem H Tran; Hieu S Vu; Eunus S Ali; Halie Rion; Brendan P O'Hara; Sherwin Kelekar; James Hughes Hallett; Misty Martin; Thomas P Mathews; Peng Gao; John M Asara; Brendan D Manning; Issam Ben-Sahra; Gerta Hoxhaj Journal: Nat Commun Date: 2022-05-16 Impact factor: 17.694
Authors: Jelena Živković; Milan Ilić; Katarina Šavikin; Gordana Zdunić; Aleksandra Ilić; Dejan Stojković Journal: Front Pharmacol Date: 2020-07-08 Impact factor: 5.810