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 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32580