Chebulagic acid Chebulinic acid and Gallic acid, the active principles of Triphala, inhibit TNFα induced pro-angiogenic and pro-inflammatory activities in retinal capillary endothelial cells by inhibiting p38, ERK and NFkB phosphorylation

Autor: Sivasankar Shanmuganathan, Narayanasamy Angayarkanni
Rok vydání: 2018
Předmět:
0301 basic medicine
Chebulinic acid
Time Factors
Physiology
Angiogenesis
medicine.medical_treatment
Anti-Inflammatory Agents
Neovascularization
Physiologic
Angiogenesis Inhibitors
Chick Embryo
Pharmacology
Retinal Neovascularization
p38 Mitogen-Activated Protein Kinases
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Glucosides
Gallic Acid
medicine
Animals
Benzopyrans
Viability assay
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Tube formation
Dose-Response Relationship
Drug
Chemistry
Plant Extracts
Tumor Necrosis Factor-alpha
NF-kappa B
Endothelial Cells
Retinal Vessels
Macaca mulatta
Hydrolyzable Tannins
Molecular Docking Simulation
030104 developmental biology
Cytokine
Matrix Metalloproteinase 9
Receptors
Tumor Necrosis Factor
Type I
Chebulagic acid
Molecular Medicine
sense organs
Inflammation Mediators
Triphala
Ex vivo
Protein Binding
Signal Transduction
Zdroj: Vascular pharmacology. 108
ISSN: 1879-3649
Popis: Tumor necrosis factor-α (TNFα) a pleiotropic cytokine induces pro-inflammatory and pro-angiogenic changes in conditions such as diabetic retinopathy (DR) and neovascular age related macular degeneration (NV-AMD). Hence, inhibition of TNFα mediated changes can benefit the management of DR and NV-AMD. Triphala, an ayurvedic herbal preparation is known to have immunomodulatry functions. In this study we evaluated the alcoholic extract of triphala (AlE) and its compounds Chebulagic acid (CA), Chebulinic acid (CI) and Gallic acid (GA) for their anti-TNFα activity. TNFα induced pro-inflammatory and pro-angiogenic changes in the retinal-choroid microvascular endothelial cells (RF/6A). Treatment with CA/CI/GA and the whole Triphala extract showed characteristic inhibition of MMP-9, cell proliferation/migration and tube formation as well the expression of IL-6, IL-8 and MCP-1 without affecting cell viability. This was mediated by inhibition of p38, ERK and NFκB phosphorylation. Ex vivo angiogenesis assay using chick chorioallantoic membrane (CAM) model also showed that TNFα-induced angiogenesis and it was inhibited by AlE and its active principles. Further, in silico studies revealed that CA, CI and GA are capable of binding the TNFα-receptor-1 to mediate anti-TNFα activity. This study explains the immunomodulatory function of Triphala, evaluated in the context of retinal and choroid vasculopathies in vitro and ex vivo; which showed that CA, CI and GA can be a potential pharmacological agents in the management of DR and NV-AMD.
Databáze: OpenAIRE
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