X-Message-Number: 32580
Date: Thu, 6 May 2010 21:14:45 -0700 (PDT)
From: 
Subject: Kaempferol may inhibit aging

[Kaempferol appears to be the flavonoid of choice for antiaging purposes.]

Age (Dordr). 2010 Jun;32(2):197-208. Epub 2010 Jan 13.

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

Kim JM, Lee EK, Kim DH, Yu BP, Chung HY. Department of Pharmacy, College of 
Pharmacy, Pusan National University, San 30, Jangjun-dong, Gumjung-gu, Busan 
609-735, Korea.
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-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.
PMID: 20431987

Biosci Biotechnol Biochem. 2010 Feb 23;74(2):397-401. Epub 2010 Feb 7.

Protective effects of kaempferol (3,4',5,7-tetrahydroxyflavone) against amyloid 
beta peptide (Abeta)-induced neurotoxicity in ICR mice.

Kim JK, Choi SJ, Cho HY, Hwang HJ, Kim YJ, Lim ST, Kim CJ, Kim HK, Peterson S, 
Shin DH. Department of Food and Biotechnology, Korea University, Seoul, Republic
of Korea.
Abstract

    To determine the effects of kaempferol, rat pheochromocytoma cells (PC12) 
    and Institute of Cancer Research (ICR) mice were utilized as neuronal 
    models. Using in vitro assays, kaempferol was shown to have protective 
    effects against oxidative stress-induced cytotoxicity in PC12 cells. 
    Administration of kaempferol also significantly reversed amyloid beta 
    peptide (Abeta)-induced impaired performance in a Y-maze test. Taken 
    altogether, the results reported here suggest that further investigation is 
    warranted of the influence of kaempferol on pathways related to Alzheimer's 
    disease.
PMID: 20139605
Free text>
http://www.jstage.jst.go.jp/article/bbb/74/2/397/_pdf

[Kaempferol was the only flavonoid which reduced burn-induced skin injuries.]

BMB Rep. 2010 Jan;43(1):46-51.
Protection of burn-induced skin injuries by the flavonoid kaempferol.

Park BK, Lee S, Seo JN, Rhee JW, Park JB, Kim YS, Choi IG, Kim YE, Lee Y, Kwon 
HJ. Department of Microbiology, College of Medicine, Hallym University, 
Chuncheon 200-702, Korea.
Abstract

    Thermal burn injury induces inflammatory cell infiltrates in the dermis and 
    thickening of the epidermis. Following a burn injury, various mediators, 
    including reactive oxygen species (ROS), are produced in macrophages and 
    neutrophils, exposing all tissues to oxidative injury. The anti-oxidant 
    activities of flavonoids have been widely exploited to scavenge ROS. In this
    study, we observed that several flavonoids-kaempferol, quercetin, fisetin, 
    and chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells.
    In contrast with quercetin and fisetin, pretreatment of kaempferol and 
    chrysin did not decrease cell viability. Inflammatory cell infiltrates in 
    the dermis and thickening of the epidermis induced by burn injuries in mice 
    was relieved by kaempferol treatment. However, the injury was worsened by 
    fisetin, quercetin, and chrysin. Expression of TNF-a induced by burn 
    injuries was decreased by kaempferol. These findings suggest the potential 
    use of kaempferol as a therapeutic in thermal burn-induced skin injuries. 
    [BMB reports 2010; 43(1): 46-51].
PMID: 20132735
Free text>
http://www.bmbreports.org/fulltext/bmbreports/view.php?vol=43&page=46

[However there appears to be a synergism between kaempferol and chrysin.]

Inflamm Res. 2010 Mar 11. [Epub ahead of print]

Flavonoid combinations cause synergistic inhibition of proinflammatory mediator 
secretion from lipopolysaccharide-induced RAW 264.7 cells.

Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, Harith HH, 
Zakaria ZA, Mohamad AS, Sulaiman MR, Israf DA. Department of Biomedical Science,
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, 
Serdang, Selangor, Malaysia.
Abstract

    OBJECTIVES: We evaluated several flavonoid combinations for synergy in the 
    inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular 
    model of inflammation. METHODS: The inhibitory effect of chrysin, 
    kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric 
    oxide (NO), prostaglandin E(2) (PGE(2)) and tumour necrosis factor-alpha 
    (TNF-alpha) secretion from the LPS-induced RAW 264.7 monocytic macrophage 
    was assessed and IC(50) values obtained. Flavonoids that showed reasonable 
    inhibitory effects in at least two out of the three assays were combined in 
    a series of fixed IC(50) ratios and reassessed for inhibition of NO, PGE(2) 
    and TNF-alpha. Dose-response curves were generated and interactions were 
    analysed using isobolographic analysis. RESULTS: The experiments showed that
    only chrysin, kaempferol, morin, and silibinin were potent enough to 
    produce dose-response effects upon at least two out of the three mediators 
    assayed. Combinations of these four flavonoids showed that several 
    combinations afforded highly significant synergistic effects. CONCLUSIONS: 
    Some flavonoids are synergistic in their anti-inflammatory effects when 
    combined. In particular chrysin and kaempferol significantly synergised in 
    their inhibitory effect upon NO, PGE(2) and TNF-alpha secretion. These 
    findings open further avenues of research into combinatorial therapeutics of
    inflammatory-related diseases and the pharmacology of flavonoid synergy.
PMID: 20221843

J Neurochem. 2009 Oct;111(2):473-87. Epub 2009 Aug 13.

Kaempferol protects against rat striatal degeneration induced by 
3-nitropropionic acid.

Lagoa R, Lopez-Sanchez C, Samhan-Arias AK, Ganan CM, Garcia-Martinez V, 
Gutierrez-Merino C. Human Anatomy and Embryology, Faculty of Medicine, 
University of Extremadura, Badajoz, Spain.
Abstract

    3-Nitropropionic acid (NPA) produces degeneration of striatum and some 
    neurological disturbances characteristic of Huntington's disease in rodents 
    and primates. We have shown that the flavonoid kaempferol largely reduced 
    striatal damage induced by cerebral ischaemia-reperfusion in rats 
    (Lopez-Sanchez et al. 2007). In this work, we report that intraperitoneal 
    (i.p.) administration of kaempferol affords an efficient protection against 
    NPA-induced neurodegeneration in Wistar rats. We studied the effects of 
    daily i.p. injections of 7, 14 and 21 mg of kaempferol/kg body weight during
    the NPA-treatment (25 mg/kg body weight/12 h i.p., for 5 days) on the 
    neurological deficits, degeneration of rat striatum and oxidative stress 
    markers. Intraperitoneal injections of 14-21 mg of kaempferol/kg body weight
    largely attenuated motor deficit and delayed mortality. The higher dose of 
    kaempferol prevented the appearance of NPA-induced striatal lesions up to 
    the end of treatment, as revealed by haematoxylin-eosin and TUNEL staining, 
    and also NPA-induced oxidative stress, because it blocked the fall of 
    reduced glutathione and the increase of protein nitrotyrosines in 
    NPA-treated rats. It was found that striatal degeneration was associated 
    with calpains activation and a large inactivation of creatine kinase, which 
    were also prevented when the higher doses of kaempferol were administered.
PMID: 19682208

J Med Food. 2009 Apr;12(2):351-8.

The anti-inflammatory effect of kaempferol in aged kidney tissues: the 
involvement of nuclear factor-kappaB via nuclear factor-inducing kinase/IkappaB 
kinase and mitogen-activated protein kinase pathways.

Park MJ, Lee EK, Heo HS, Kim MS, Sung B, Kim MK, Lee J, Kim ND, Anton S, Choi 
JS, Yu BP, Chung HY. Department of Pharmacy, College of Pharmacy, Pusan National
University, Busan, Republic of Korea.
Abstract

    Kaempferol, one of the phytoestrogens, is found in berries and Brassica and 
    Allium species and is known to have antioxidative and anti-inflammatory 
    properties. In the present study, we examined the molecular mechanisms 
    underlying the anti-inflammation effect of kaempferol in an aged animal 
    model. To examine the effect of kaempferol in aged Sprague-Dawley rats, 
    kaempferol was fed at 2 or 4 mg/kg/day for 10 days. The data show that 
    kaempferol exhibited the ability to maintain redox balance. Kaempferol 
    suppressed nuclear factor-kappaB (NF-kappaB) activation and expression of 
    its target genes cyclooxygenase-2, inducible nitric oxide synthase, monocyte
    chemoattractant protein-1, and regulated upon activation, and normal T-cell
    expressed and secreted in aged rat kidney and in 
    tert-butylhydroperoxide-induced YPEN-1 cells. Furthermore, kaempferol 
    suppressed the increase of the pro-inflammatory NF-kappaB cascade through 
    modulation of nuclear factor-inducing kinase (NIK)/IkappaB kinase (IKK) and 
    mitogen-activated protein kinases (MAPKs) in aged rat kidney. Based on these
    results, we concluded that anti-oxidative kaempferol suppressed the 
    activation of inflammatory NF-kappaB transcription factor through NIK/IKK 
    and MAPKs in aged rat kidney.
PMID: 19459737

[Eat your greens.]

J Agric Food Chem. 2009 Aug 26;57(16):7401-8.

Identification of the phenolic components of collard greens, kale, and Chinese 
broccoli.

Lin LZ, Harnly JM. Food Composition and Methods Development Laboratory, 
Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. 
Department of Agriculture, Building-161, BARC-East, Beltsville, Maryland 20705, 
USA.
Abstract

    An LC-MS profiling method was used for a comprehensive study of the phenolic
    components of collard greens, kale, and Chinese broccoli, three Brassica 
    green leafy vegetables. This study led to the identification of 45 
    flavonoids and 13 hydroxycinnamic acid derivatives in the three vegetables. 
    Most of the identifications were based on comparison of compounds previously
    reported in the literature for Brassica vegetables. The results indicate 
    that the three materials have very similar phenolic component profiles. For 
    each, kaempferol glycosides and acylgentiobiosides were the major phenolic 
    compounds, quercetin glycosides were minor compounds, and most of the 
    flavononol glycosides existed in their acylated forms. In addition, each of 
    the materials contained caffeoyl-, p-coumaroyl-, and feruloylquinic acid 
    monomers with a 3-position derivative as the dominant isomer. This is the 
    first report for most of these phenolics in collard greens and Chinese 
    broccoli and for >20 of them in kale.
PMID: 19627150

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