Kesavan R, Chandel S, Upadhyay S, Bendre R, Ganugula R, Potunuru U R, Giri H, Sahu G, Kumar P Uday, Reddy G Bhanuprakash, Joksic G, Bera A K, Dixit Madhulika
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering Building, Indian Institute of Technology Madras, Chennai 600036, India.
National Institute of Nutrition, Hyderabad, India.
Nutr Metab Cardiovasc Dis. 2016 Apr;26(4):293-301. doi: 10.1016/j.numecd.2015.12.016. Epub 2016 Jan 6.
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 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.
Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities.
研究表明,黄龙胆(GL)及其成分异荭草苷可能具有抗动脉粥样硬化特性。在本研究中,我们试图探究GL根水提取物和异荭草苷对链脲佐菌素(STZ)诱导的糖尿病大鼠内皮炎症、平滑肌细胞迁移以及动脉粥样硬化发生和发展的保护机制。
我们的结果显示,GL提取物和异荭草苷分别在肿瘤坏死因子-α(TNF-α)和血小板衍生生长因子-BB(PDGF-BB)刺激后,可阻断人脐静脉内皮细胞(HUVECs)和大鼠主动脉平滑肌细胞(RASMCs)中的白细胞黏附和活性氧生成。提取物和异荭草苷均阻断了TNF-α诱导的HUVECs中细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的表达。GL提取物和异荭草苷也消除了PDGF-BB诱导的RASMCs迁移和磷脂酶C-γ激活。基于Fura-2的比率测量表明,提取物和异荭草苷均抑制PDGF-BB介导的RASMCs细胞内钙升高。用2%GL根粉补充STZ大鼠的常规饮食可降低血液中的总胆固醇。油红O染色显示,用GL治疗后糖尿病动物主动脉壁中的脂质积累减少。补充后糖尿病大鼠主动脉段的中层厚度和胶原蛋白沉积也减少。免疫组织化学显示,GL治疗后糖尿病大鼠主动脉段中血管细胞黏附分子-1(VCAM-1)、诱导型一氧化氮合酶(iNOS)和血管内皮钙黏蛋白(VE-cadherin)的表达降低。
因此,我们的结果支持GL根提取物/粉末和异荭草苷具有抗动脉粥样硬化活性。