Antiatherogenic Effects of Kaempferol and Rhamnocitrin

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall. Kaempferol and rhamnocitrin (kaempferol 7-O-methyl ether) are two anti-inflammatory flavonoids commonly found in plants. The aim of this study is to investigate the function of kaempferol and rhamnocitrin on prevention of atherosclerosis. Chemical analyses demonstrated that kaempferol and rhamnocitrin were scavengers of DPPH (1,1-diphenyl-2-picrylhydrazyl) with IC50 of 26.10 +/- 1.33 and 28.38 +/- 3.07 microM, respectively. Copper-induced low-density lipoprotein (LDL) oxidation was inhibited by kaempferol and rhamnocitrin, with similar potency, as measured by decreased formation of malondialdehyde and relative electrophoretic mobility (REM) on agarose gel, while rhamnocitrin reduced delayed formation of conjugated dienes better than kaempferol. Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low-density lipoprotein (oxLDL), is found in atherosclerotic lesions, and is up-regulated by oxLDL. Addition of kaempferol and rhamnocitrin (20 microM) caused significant reductions in cell surface CD36 protein expression in THP-1-derived macrophages (p < 0.05). Reverse transcription quantitative PCR (RT-Q-PCR) showed that kaempferol and rhamnocitrin (20 microM) decreased oxLDL-induced CD36 mRNA expression (p < 0.01 and p < 0.05, respectively). Kaempferol- and rhamnocitrin-treated macrophages also showed reduction in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled oxLDL uptake. Current evidences indicate that kaempferol and rhamnocitrin not only protect LDL from oxidation but also prevent atherogenesis through suppressing macrophage uptake of oxLDL.

Standardized Flavonoid-Rich Eugenia jambolana Seed Extract Retards In Vitro and In Vivo LDL Oxidation and Expression of VCAM-1 and P-Selectin in Atherogenic Rats

“…In the present context, quercetin, rutin, and kaempferol present in EJSE can be considered to be instrumental in protecting the LDL from undergoing Cu 2? -mediated oxidation [25,26].…”

Sensitive determination of kaempferol in rat plasma by high-performance liquid chromatography with chemiluminescence detection and application to a pharmacokinetic study

“…They are subdivided into six classes: flavones, flavanones, isoflavones, flavonols, flavanols, and anthocyanins varying in their structure characteristics around the heterocyclic oxygen ring [1]. Kaempferol (3,5,7,4 -tetrahydroxy flavone), a major representative of the flavonol subclass, has received much attention during the past few years because of its anticarcinogenic [2,3], antiatherogenic [4], antioxidant [5], antiphlogistic [6], and osteogenic properties [7]. In order to better understand the pharmacological effects of flavonols, researchers have sought to perform their pharmacokinetic studies [8].…”

Microbial Metabolism of Biologically Active Secondary Metabolites from Nerium oleander L.

“…19) Kaempferol represents one of the most potent antioxidant drugs isolated from natural sources. 20,21) Kaempferol was also found to possess antiatherogenic, 22) anti-inflammatory 23) as well as antidepressant activities. 24) An important factor in the evaluation of safety and efficacy of a drug is the knowledge of how the drug is metabolized.…”