Uma Rani Potunuru

Bio: Uma Rani Potunuru is an academic researcher from Indian Institute of Technology Madras. The author has contributed to research in topics: Isovitexin & Somatic cell. The author has an hindex of 5, co-authored 5 publications receiving 116 citations.

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.

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

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 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.

Role of Polyphenols and Other Phytochemicals on Molecular Signaling

Abstract: Optimized nutrition through supplementation of diet with plant derived phytochemicals has attracted significant attention to prevent the onset of many chronic diseases including cardiovascular impairments, cancer, and metabolic disorder. These phytonutrients alone or in combination with others are believed to impart beneficial effects and play pivotal role in metabolic abnormalities such as dyslipidemia, insulin resistance, hypertension, glucose intolerance, systemic inflammation, and oxidative stress. Epidemiological and preclinical studies demonstrated that fruits, vegetables, and beverages rich in carotenoids, isoflavones, phytoestrogens, and phytosterols delay the onset of atherosclerosis or act as a chemoprotective agent by interacting with the underlying pathomechanisms. Phytochemicals exert their beneficial effects either by reducing the circulating levels of cholesterol or by inhibiting lipid oxidation, while others exhibit anti-inflammatory and antiplatelet activities. Additionally, they reduce neointimal thickening by inhibiting proliferation of smooth muscle cells and also improve endothelium dependent vasorelaxation by modulating bioavailability of nitric-oxide and voltage-gated ion channels. However, detailed and profound knowledge on specific molecular targets of each phytochemical is very important to ensure safe use of these active compounds as a therapeutic agent. Thus, this paper reviews the active antioxidative, antiproliferative, anti-inflammatory, or antiangiogenesis role of various phytochemicals for prevention of chronic diseases.

Cyclotides: From Structure to Function

Abstract: This Review explores the class of plant-derived macrocyclic peptides called cyclotides. We include an account of their discovery, characterization, and distribution in the plant kingdom as well as a detailed analysis of their sequences and structures, biosynthesis and chemical synthesis, biological functions, and applications. These macrocyclic peptides are around 30 amino acids in size and are characterized by their head-to-tail cyclic backbone and cystine knot motif, which render them to be exceptionally stable, with resistance to thermal or enzymatic degradation. Routes to their chemical synthesis have been developed over the past two decades, and this capability has facilitated a wide range of mutagenesis and structure-activity relationship studies. In turn, these studies have both led to an increased understanding of their mechanisms of action as well as facilitated a range of applications in agriculture and medicine, as ecofriendly crop protection agents, and as drug leads or scaffolds for pharmaceutical design. Our overall objective in this Review is to provide readers with a comprehensive overview of cyclotides that we hope will stimulate further work on this fascinating family of peptides.

Molecular targets of vitexin and isovitexin in cancer therapy: a critical review.

Abstract: Cancer is a primary public health problem and the second leading cause of death worldwide. It causes life-threatening malignancies and results in high financial costs for both patients and the healthcare system. Hence, it is important to develop effective long-term strategies pertaining to prevention and control of cancers. Plant-derived secondary metabolites have been shown to have positive roles against various cancers. A number of plant extracts have been evaluated for possible use in the treatment of cancer; some have provided direction for new strategies for the research and development of antitumor agents. Here, we provide comprehensive data on various cancers, potential molecular mechanisms, and therapeutic implications of just two plant-derived compounds, vitexin and isovitexin. Information on the chemotherapeutic potential of vitexin and isovitexin was collected from a library database and through electronic searches (ScienceDirect, Pubmed, and Google Scholar). Both in vitro and in vivo studies suggest that vitexin and isovitexin are chemopreventive compounds with activity against various cancers through proapoptotic processes and/or autophagy.