title: Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts.
abstract: Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.
authors: Laboratory of Vascular Biology, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
authors: Rushendhiran
authors: R
authors: Kesavan
authors: Uma Rani
authors: UR
authors: Potunuru
authors: Branislav
authors: B
authors: Nastasijević
authors: Avaneesh
authors: A
authors: T
authors: Gordana
authors: G
authors: Joksić
authors: Madhulika
authors: M
authors: Dixit
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D030012:Gentiana / Q000737:chemistry*; D048369:MAP Kinase Kinase 1 / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010936:Plant Extracts; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D047310:Apigenin; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C049772:isovitexin
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