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Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase

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Abstract

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-ĸB). 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-ĸB 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-κB activity and NF-ĸB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-κB 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-κB 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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Acknowledgements

This work was supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (20090093226). We thank Aging Tissue Bank for providing research samples.

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Authors and Affiliations

  1. Department of Pharmacy, College of Pharmacy, Pusan National University, San 30, Jangjun-dong, Gumjung-gu, Busan, 609-735, Korea

    Ji Min Kim, Eun Kyeong Lee, Dae Hyun Kim & Hae Young Chung

  2. Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, South Korea

    Byung Pal Yu & Hae Young Chung

  3. Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA

    Byung Pal Yu

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  1. Ji Min Kim
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  2. Eun Kyeong Lee
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Correspondence to Hae Young Chung.

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Kim, J.M., Lee, E.K., Kim, D.H. et al. Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase. AGE 32, 197–208 (2010). https://doi.org/10.1007/s11357-009-9124-1

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  • DOI: https://doi.org/10.1007/s11357-009-9124-1

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