title: Kaempferol inhibits the production of ROS to modulate OPN-αvβ3 integrin pathway in HUVECs.
abstract: In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor κB (NF-κB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-κB, OPN, alphavbeta3 (αvβ3) integrin, and inhibitor of NF-κB alpha phosphorylation (P-IκBα) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 μM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-κB, IL-6, and TNF-α levels; Nox4, αvβ3 integrin; and P-IκBα expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 μg/mL) treatment decreased expressions of OPN, αvβ3 integrin, and NF-κB (P < 0.05 or P < 0.01). The present results suggest that kaempferol may modulate OPN-αvβ3 integrin pathway to inhibit NF-κB activation in HUVECs.
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Furong District, Changsha, 410128, China. xhbzhb@yahoo.com.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xiao
authors.affiliation: Hunan Province University Key Laboratory for Agricultural Biochemistry and Biotransformation, Hunan Agricultural University, Changsha, 410128, China.|Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, 410128, China.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Lu
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University, Furong District, Changsha, 410128, China.
authors.forename: Zi-Kui
authors.initials: ZK
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Xiangnan University, Chenzhou, 423000, China.|The Third Hospital of Changsha, Changsha, 410015, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Luo
mesh_terms: D000450:Aldosterone / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D039564:Integrin alphaV / Q000737:chemistry / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D039661:Integrin beta3 / Q000737:chemistry / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D053495:Osteopontin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D000975:Antioxidants; C061248:ITGB3 protein, human; D018836:Inflammation Mediators; D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D044949:Kaempferols; C000614691:LM609 monoclonal antibody; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C506895:SPP1 protein, human; D053495:Osteopontin; D013148:Spironolactone; D000450:Aldosterone; C006552:kaempferol; D001205:Ascorbic Acid
keywords: Aldosterone; Human umbilical vein endothelial cells; Kaempferol; Nuclear factor κB; Osteopontin; αvβ3 Integrin