Down-regulation of iNOS and TNF-α expression by kaempferol via NF-κB inactivation in aged rat gingival tissues

Abstract

The primary objective of this study was to evaluate the ability and mechanism of action of kaempferol, which is contained in extracts from Nelumbo nucifera, a well-known Oriental herb used in traditional medicine, with regard to the inhibition of iNOS and TNF-alpha expression in aged rat gingival tissues. We conducted an investigation into the age-related effects of kaempferol on reactive oxygen species (ROS) and GSH oxidative status in samples of aged gingival tissues. Western blotting was conducted in order to determine the expression of iNOS, TNF-alpha, p38 MAPK, NIK/IKK, p65 and IkappaBalpha in the sample tissues. Electrophoretic mobility shift assays (EMSA) were conducted in an effort to characterize the binding activities of NF-kappaB transcription factors in the aged rat gingival nuclear extracts. Our results indicate that kaempferol reduced ROS levels and augmented GSH levels in a dose-dependent manner in the aged gingival tissues. Kaempferol was shown to effect a significant reduction in iNOS and TNF-alpha protein levels, as compared to control gingival tissue samples. The results of Western blot analysis revealed that kaempferol treatment effected the reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues, attenuated the NF-kappaB nuclear binding activity. Kaempferol may inhibit ROS generation via the inhibition of iNOS and TNF-alpha expression in aged gingival tissues, via the modulation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways.

β-Arrestin-1 protects against endoplasmic reticulum stress/p53-upregulated modulator of apoptosis-mediated apoptosis via repressing p-p65/inducible nitric oxide synthase in portal hypertensive gastropathy

“…In this study, an elevated TNF-α level induced the expression of iNOS and increased NO concentrations in PHG, which was aggravated by E-arr1 deficiency. Moreover, the pivotal elements of NF-κB, p65, which could enhance iNOS [25,26], was also activated in PHG mucosa, and this was exacerbated by E-arr1 deficiency. These results were consistent with TNF-α regulation of iNOS expression via p65 activation.…”

“…NF-κB is a complex of dimeric subunits that belong to the NF-NB/Rel family: NF-κB1 (p50 and its precursor p105), NF-κB2 (p52 and its precursor p100), p65 (RelA), RelB and c-Rel [24]. As the main functional element, p65 was involved in regulation of various physiological and pathological events, and p65 activation was involved in reperfusion injury and iNOS gene regulation in pancreatic β-cells, gingival tissues, and intestinal cells [19,25,26].…”

Transcriptional profiling in human HaCaT keratinocytes in response to kaempferol and identification of potential transcription factors for regulating differential gene expression

“…In addition, our observations are consistent with previous reports, which demonstrated that kaempferol blocked TNFα-induced translocation of the NF-κB subunit p65 from the cytoplasm to the nucleus in mouse primary calvarial osteoblasts (Pang et al, 2006) and downregulate iNOS and TNFα expression via NF-κB inactivation in aged rat gingival tissues . Kim et al (2007) showed the inhibitory effects of kaempferol against the aging process such as inflammation in gingival tissues and demonstrated the underlying molecular mechanisms. We predicted the NF-κB family signal as one putative regulatory network from the epidermal genes regulated differentially by kaempferol using bioinformatic methods and confirmed the prediction with the ELISA-based transcription factor assay.…”

Effects of Antioxidants on Periodontal Disease

“…Mangiferin (C2-β-d -glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is widely distributed in higher plants, has antioxidant capacity [ 253 ], and reduces the alveolar bone loss of rats with experimental periodontitis [ 29 ]. Kaempferol (3,4,5,7-tetrahydroxyfl avone), a fl avonoid glycoside which is particularly abundant in fruits, vegetables, and beverages such as tea [ 254 ], attenuated the NF-κB nuclear binding activity in rat gingival tissue [ 255 ]. Pycnogenol is a water-soluble mixture of fl avonoid compounds extracted from French maritime pine bark and chewing gum containing this compound minimizes gingival bleeding and plaque formation in humans [ 256 ].…”