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Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase
Open accessAbstract
Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-kB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-kB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-kappaB activity and NF-kB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-kappaB activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-kappaB signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies.
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“Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds (Table 3) [228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [229]
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Metadata
- Authors
- Kim, J. M., Lee, E. K., Kim, D. H., Yu, B. P., & Chung, H. Y.
- Affiliations
- Pusan National University (KR)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Chung, Hae Young
- Venue
- AGE
- Published
- 2010-01-13
- Volume
- 32
- Issue
- 2
- Pages
- 197-208
- ISSN
- 0161-9152 (ISSN-L)
- 1574-4647
- PMC
- PMC2861750
- OpenAlex
- W1989395374
- Cited by
- 133
- References
- 50
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 13 · 2020: 8 · 2019: 11 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 10 · 2014: 3 · 2013: 2 · 2012: 6
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- AGE (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Keywords
- kaempferol, advanced glycation end products, NF-κB activation, NADPH oxidase, AGE receptor, aging, oxidative stress, inflammation, dietary supplementation, kidney, endothelial cells
- MeSH terms
- Animals, Antioxidants, Kidney, Male, Rats, Inbred F344, Transfection, Blotting, Western, NF-kappa B, Glycation End Products, Advanced, Reactive Oxygen Species, NADPH Oxidases, Kaempferols, Rats
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