title: Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs.
abstract: Previous studies revealed the potent anti-inflammatory activity of tricin, the active component of Njavara rice bran. Here, we report the involvement of specific signaling pathways in the protective effect of tricin against LPS induced inflammation in hPBMCs and the role of tricin in modulating endothelial dysfunction in LPS induced HUVECs. Pretreatment with tricin (15μM) significantly inhibited the release of TNF-α and was comparable to the specific pathway blockers like ERK inhibitor (PD98059), JNK inhibitor (SP600125) and p38 inhibitor (SB203580), whereas an increased release of TNF-α was observed in PI3K/Akt inhibitor (LY294002) treated cells. Tricin alone and combination treatment of tricin and SB203580 showed more significant inhibition of activation of COX-2 and TNF-α than that of SB203580 alone treated group. Combination treatment of tricin and LY294002 showed increased activation of COX-2 and TNF-α, proved that PI3K activation is essential for the anti-inflammatory effect of tricin. Studies conducted on HUVECs revealed the protective effect of tricin against endothelial dysfunction associated with LPS induced inflammation by inhibiting the activation of proinflammatory mediators like TNF-α, IFN-γ, MCP 1 by modulating NF-κB and MAPK signaling pathways. ELISA and flow cytometric analysis again confirmed the protection of tricin against endothelial damage, especially from the decreased activation of cell adhesion molecules like ICAM-1, VCAM-1 and E-Selectin upon tricin treatment. This work establishes the mechanism behind the potent anti-inflammatory activity of the flavonoid tricin.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthpuram, 695581 Kerala, India. Electronic address: bioshalu@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Shalini
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthpuram, 695581 Kerala, India.
authors.forename: Chithra K
authors.initials: CK
authors.lastname: Pushpan
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthpuram, 695581 Kerala, India.
authors.forename: Sindhu
authors.initials: S
authors.lastname: G
authors.affiliation: Chemical Sciences & Technology Division, National Institute for Interdisciplinary Science and Technology (NIIST), CSIR, Industrial Estate P.O., Thiruvananthapuram, 695019 Kerala, India. Electronic address: Jayalekshmy_a@yahoo.com.
authors.forename: Jayalekshmy
authors.initials: J
authors.lastname: A
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthpuram, 695581 Kerala, India. Electronic address: helen_biochem@yahoo.com.
authors.forename: Helen
authors.initials: H
authors.lastname: A
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D019040:E-Selectin / Q000235:genetics / Q000276:immunology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D012275:Oryza / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D051546:Cyclooxygenase 2; D019040:E-Selectin; D005419:Flavonoids; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D048670:MAP Kinase Kinase 4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; C111835:CCL2 protein, human; C573420:ICAM1 protein, human; C017769:tricin; C496540:PTGS2 protein, human; C535150:MAPK1 protein, human
keywords: Flavonoid; Inflammation; Lipopolysaccharide; Signaling; Tricin