 Chemical Structure.png)
Kaempferol (Kempferol; Robigenin), a naturally occuring flavonoid analog, is a potent ERRα (estrogen receptor α) and ERRγ inverse agonist. It prevents DNA replication that is catalyzed by topoisomerase I and may also prevent fatty acid synthase from working. Additionally, by inhibiting the expression of cyclo-oxygenase 2 and interleukin-4, kaempferol reduces inflammation by downregulating the NFκB pathway and suppressing Src kinase. Additionally useful in ovarian cancer cell inhibition of angiogenesis and induction of apoptosis is kaempferol.
Physicochemical Properties
| Molecular Formula | C15H10O6 | |
| Molecular Weight | 286.23 | |
| Exact Mass | 286.047 | |
| Elemental Analysis | C, 62.94; H, 3.52; O, 33.54 | |
| CAS # | 520-18-3 | |
| Related CAS # |
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| PubChem CID | 5280863 | |
| Appearance | Light yellow to yellow solid powder | |
| Density | 1.7±0.1 g/cm3 | |
| Boiling Point | 582.1±50.0 °C at 760 mmHg | |
| Melting Point | 276°C | |
| Flash Point | 226.1±23.6 °C | |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C | |
| Index of Refraction | 1.785 | |
| LogP | 2.05 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 21 | |
| Complexity | 451 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | OC1=C2C(OC(C3=CC=C(O)C=C3)=C(O)C2=O)=CC(O)=C1 |
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| InChi Key | IYRMWMYZSQPJKC-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C15H10O6/c16-8-3-1-7(2-4-8)15-14(20)13(19)12-10(18)5-9(17)6-11(12)21-15/h1-6,16-18,20H | |
| Chemical Name | 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one | |
| Synonyms | 3,4',5,7-Tetrahydroxyflavone; Pelargidenolon; Indigo Yellow; Kaempferol; Campherol | |
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
ERRα; ERRγ; Topo I; fatty acid synthase Kaempferol (Kempferol; Robigenin) targets p53 (intrinsic apoptotic pathway) [2] Kaempferol (Kempferol; Robigenin) targets calcium/calmodulin-dependent protein kinase II (CaMKII, deoxidization-related, ) [3] Kaempferol (Kempferol; Robigenin) modulates airway smooth muscle cell proliferation and allergic inflammation-related pathways [4] |
| ln Vitro |
Kaempferol also inhibits the expression of cyclo-oxygenase 2 and interleukin-4 by downregulating the NFκB pathway and suppressing Src kinase. This results in anti-inflammatory effects. Additionally, kaempferol works well to stop angiogenesis and cause ovarian cancer cells to die. A natural flavonoid found in many fruits and vegetables, kaempferol has been shown in long-term studies to significantly and dramatically lower the risk of ovarian cancer in female American nurses working in nursing over several decades. Kaempferol significantly and concentration-dependently inhibits the proliferation of all three tested ovarian cancer cells after a 24-hour treatment. At treatment concentrations of 40 μM or above, this inhibition is seen. Kaempferol is a flavonoid that is widely found in many foods made from plants and leaves that are used in traditional medicine. Significantly, kaempferol inhibits the activity of NADPH oxidase. Reactive oxygen species (ROS) are reduced by kaempferol through direct binding of NADPH oxidase. Kaempferol inhibits CAMKII oxidation, which stops Ang II from inducing sinus nodal cell death. The release of Kaempferol in sensitized RBL-2H3 cells is dose-dependently suppressed by 10–20 μM of the drug. The activation of Syk and PLCγ is greatly reduced in DNP-BSA-challenged RBL-2H3 cells when 10–20 μM Kaempferol is added for 15 minutes. The COX2 induction is diminished in DNP-BSA-challenged RBL-2H3 cells when ≥10 μM Kaempferol is added for 60 minutes. Kaempferol (Kempferol; Robigenin) nanoparticles (10-80 μM) dose-dependently inhibited viability of human ovarian cancer cells (SKOV3, A2780) with IC50 values of 32 μM (SKOV3) and 28 μM (A2780), while showing minimal toxicity to normal human ovarian epithelial cells (IC50 > 100 μM). It induced G2/M cell cycle arrest and apoptosis, as evidenced by increased Annexin V-positive cells and caspase-3 activation [1] Kaempferol (Kempferol; Robigenin) (20-80 μM) induced apoptosis in A2780 ovarian cancer cells via activating the intrinsic p53 pathway. It upregulated p53 and Bax mRNA/protein expression, downregulated Bcl-2 expression, and increased caspase-9 and caspase-3 cleavage. At 80 μM, apoptotic rate reached 42.3% compared to 5.1% in the control group [2] Kaempferol (Kempferol; Robigenin) (10-50 μM) protected rat cardiac sinus node cells from hydrogen peroxide (H2O2)-induced injury. It reduced CaMKII oxidation (by 35-60% at 30-50 μM), increased cell viability (from 58% to 82% at 50 μM), and decreased apoptotic rate (from 38% to 12% at 50 μM) via inhibiting mitochondrial dysfunction [3] Kaempferol (Kempferol; Robigenin) (5-25 μM) dose-dependently inhibited proliferation of human airway smooth muscle cells (HASMCs) induced by platelet-derived growth factor (PDGF). It reduced cyclin D1 and PCNA protein expression, and suppressed production of pro-inflammatory cytokines (IL-4, IL-13, TNF-α) in LPS-stimulated RAW 264.7 macrophages [4] |
| ln Vivo |
BALB/c mice challenged with BSA have confirmed COX2 induction in their airways. The untreated control mice's airways were found to be devoid of COX2. When mice are given BSA orally, their airways become more inducible of COX2 (dark brown staining), which can be counteracted by giving them kaempferol orally also. Epithelial thickening and a noticeable hyperplasia of goblet cells are seen in mice given BSA. In mice given BSA, the epithelial thickening totally vanished when given 20 mg/kg of kaempferol supplementation. Kaempferol (Kempferol; Robigenin) (50 mg/kg/day, oral) improved cardiac sinus node dysfunction in rats with ischemia-reperfusion injury. It increased sinus node heart rate (from 285 ± 22 bpm to 368 ± 25 bpm), shortened sinus node recovery time (from 185 ± 15 ms to 132 ± 12 ms), and reduced CaMKII oxidation in sinus node tissue [3] Kaempferol (Kempferol; Robigenin) (20-80 mg/kg/day, oral) attenuated airway thickening in bovine serum albumin (BSA)-induced asthmatic mice. At 80 mg/kg, it reduced airway smooth muscle layer thickness (by 45%), peribronchial inflammatory cell infiltration (by 52%), and lung tissue levels of IL-4, IL-13, and TGF-β1. It also inhibited collagen deposition in airway walls [4] |
| Enzyme Assay |
The right atria or sinus nodal cells are homogenized in lysis buffer (50 mM Tris-HCl pH 7.5, 100 mM KCl, 1 mM ethylenediamine tetraacetic acid, 1 mM ethylene glycol tetraacetic acid, 1 mM dithiothreitol, 0.1 mM phenylmethylsulfonyl fluoride, 0.5 mM Benzamidine, 20 mg/L Leupeptin, 20 mM sodium pyrophosphate, 50 mM NaF, and 50 mM sodium β-glycerophosphate). The Bradford assay is used to quantify the total protein content. The Caspase-3 Assay Kit from EnzChek is used to measure caspase-3 activity[3]. CaMKII oxidation assay: Rat cardiac sinus node tissue was homogenized to extract total protein. The protein was incubated with H2O2 to induce oxidation, then treated with Kaempferol (Kempferol; Robigenin) (10-50 μM) for 1 hour. CaMKII oxidation level was detected by immunoblotting using an antibody specific to oxidized CaMKII. Total CaMKII expression was used as a loading control [3] Inflammatory cytokine assay: RAW 264.7 macrophages were treated with Kaempferol (Kempferol; Robigenin) (5-25 μM) for 1 hour, then stimulated with LPS for 24 hours. Culture supernatants were collected, and IL-4, IL-13, and TNF-α levels were measured by sandwich ELISA [4] |
| Cell Assay |
Triple-selected 0-160 μM Kaempferol treatment is administered for 24 hours after ovarian cancer cells seeded in 96-well plates at a density of 2000 cells/well and allowed to incubate overnight. After removing the medium, the cells are lysed by freezing and thawing the plates. To each well, 200 μL of 1× CyQUANT cell lysis buffer containing 5 times SYBR Green I is added, and it is then incubated for five minutes at room temperature (RT). A Chromo4 PCR device in real time measures the fluorescent signal at 90°C after the reaction (50 μL) has been transferred to PCR strip tubes. Genomic DNA abundance is measured after an overnight incubation period, and a standard curve is created by seeding varying numbers of OVCAR-3 cells (based on hemacytometer counts) in a 96-well plate. This ensures that cell proliferation assays are carried out within a linear range of cell numbers. Data from three separate experiments is combined for statistical analysis[2]. Ovarian cancer cell viability and apoptosis assay: SKOV3/A2780 cells and normal ovarian epithelial cells were seeded in 96-well plates, treated with Kaempferol (Kempferol; Robigenin) nanoparticles (10-100 μM) for 48 hours. Cell viability was assessed by MTT assay to calculate IC50 values. Apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry; caspase-3 activity was measured by colorimetric assay [1] p53 pathway activation assay: A2780 ovarian cancer cells were treated with Kaempferol (Kempferol; Robigenin) (20-80 μM) for 24-48 hours. Total RNA was extracted for RT-PCR to detect p53, Bax, and Bcl-2 mRNA levels. Total protein was extracted for Western blot to analyze p53, Bax, Bcl-2, pro-caspase-3, and cleaved caspase-3 expression [2] Cardiac sinus node cell protection assay: Rat cardiac sinus node cells were isolated and cultured, pretreated with Kaempferol (Kempferol; Robigenin) (10-50 μM) for 2 hours, then exposed to H2O2 for 6 hours. Cell viability was measured by CCK-8 assay; apoptosis was detected by Hoechst 33258 staining and TUNEL assay; mitochondrial membrane potential was evaluated by JC-1 staining [3] Airway smooth muscle cell proliferation assay: HASMCs were seeded in 96-well plates, synchronized with serum starvation, then treated with PDGF plus Kaempferol (Kempferol; Robigenin) (5-25 μM) for 48 hours. Cell proliferation was assessed by CCK-8 assay; cyclin D1 and PCNA protein levels were detected by Western blot [4] |
| Animal Protocol |
Mice: The four treatment groups (n=8 per group) are randomly assigned to three-week-old male BALB/c mice. (1) PBS-sensitized mice; (2) BSA-sensitized mice; (3) BSA-sensitized and 10 mg/kg Kaempferol-administered mice; and (4) BSA-sensitized and 20 mg/kg Kaempferol-administered mice. A commercial mouse chow diet consisting of 20.5% protein, 3.5% fat, 8% fiber, 8% ash, and 0.5% phosphorus is fed to the mice, and they are given unlimited access to food and water. The mice are housed in particular pathogen-free conditions with a 12-hour light and dark cycle, 23±1°C, and 50%±5% relative humidity. Prior to beginning the allergy experiments, mice are given a week to acclimate to their new environment. All experimental mice are sensitized by subcutaneous injection on days 0 and 14 with 20 μg BSA in 30 μL PBS and 50 μL inject alum. A combination of 50 μL PBS and 50 μL Imject Alum without BSA is injected into the control mice. Days 28, 29, and 30 involve giving 5% BSA inhalation only to the experimental mice that have become sensitized to it; control mice are given 5% PBS for 20 minutes in a plastic chamber that is connected to a Medel aerosol nebulizer. A full day after the final challenge, all mice are killed. Neutrophils, basophils, and eosinophils are directly counted from whole blood samples. Before being used, the right lung is kept in 4% paraformaldehyde. Myocardial ischemia-reperfusion-induced sinus node dysfunction model: Male Sprague-Dawley rats (250-300 g) were randomly divided into sham, model, and Kaempferol (Kempferol; Robigenin) treatment groups (n=8 per group). Ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 24 hours. Kaempferol was dissolved in 0.5% carboxymethylcellulose sodium (CMC-Na) and administered by oral gavage at 50 mg/kg once daily for 7 days before ischemia. Cardiac function was evaluated by electrocardiogram; sinus node tissue was collected for CaMKII oxidation and apoptosis analysis [3] BSA-induced asthmatic mouse model: Female BALB/c mice (6-8 weeks old) were randomly divided into control, asthma, and Kaempferol (Kempferol; Robigenin) treatment groups (n=6 per group). Asthma was induced by intraperitoneal injection of BSA (with adjuvant) on days 0 and 14, followed by intranasal BSA challenge on days 21-23. Kaempferol was dissolved in DMSO and diluted with physiological saline (final DMSO concentration < 0.1%), administered by oral gavage at 20, 40, or 80 mg/kg once daily from day 18 to day 23. On day 24, mice were euthanized; lung tissues were collected for histopathological analysis, cytokine detection, and collagen content measurement [4] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion The aim of this study was to assess kaempferol bioavailability in healthy humans, after bean (Phaseolus vulgaris L.) consumption through the monitoring of the excretion in relation to intake. In seven healthy subjects receiving kaempferol from cooked bean, maximum excretion of hydrolyzed flavonol was obtained after 2-8 hr. Intersexual variations in urinary excretion were found to be 6.10+/-5.50% and 5.40+/-5.40% of the kaempferol dose for male and female subjects, respectively. Although a 6.72-fold inter-individual variation between the highest and lowest excretion concentrations was found, all individuals exhibited similar excretion profiles. Moreover, a direct correlation between the percentage of kaempferol excreted and the body mass index of volunteers was observed with a correlation index equal to 0.80. All except two individuals exhibited a first peak of kaempferol excretion 2 hr after ingestion. The study reveals information about inter-individual excretion capacity after kaempferol intake and that kaempferol can be used as a biomarker for flavonol consumption. ... A pharmacokinetic study of kaempferol from endive ... /was studied in / four healthy males and four healthy females. Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 uM, at a time of 5.8 hr, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 hr. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure. Ten adult volunteers with an average age 28 years were given a single oral dose of six tablets of Ginkgo biloba extract. Quercetin and kaempferol in different period of human urine were determined by using RP-HPLC. The results showed the elimination rate constant k and the absorption rate constant ka of quercetin were slightly more than that of kaempferol; and the absorption half-life (t(1/2a)), the elimination half-life (t(1/2)) and t(max) of quercetin were less than that of kaempferol, the differences were, however, not statistically significant. The mean values of ka were 0.61 hr(-1) and 0.55 hr(-1), t(1/2a) 1.51 hr and 1.56 hr, k 0.37 hr(-1) and 0.30 hr(-1), t(1/2) 2.17 hr and 2.76 hr, T(max) 2.30 hr and 2.68 hr for quercetin and kaempferol, respectively, which mean absorption and elimination of quercetin and kaempferol are 0.17% and 0.22%, respectively. Quercetin and kaempferol are excreted in the human urine mainly as glucuronides. The objective of this study was to investigate whether kaempferol and quercetin could be transported into primary cultured cerebral neurons, to establish a practical HPLC method with UV detection for the two flavonols in the neurons, and to study the uptake and transport behaviors of them through the neurons. The present results showed that the level of kaempferol in the neurons increased linearly and then reached a plateau with incubation time at the high concentration of 10 ?g/mL, but not at the other two concentrations of 1 and 0.1 ug/mL. However, the levels of quercetin in the neurons were not detected at the three incubating concentrations, and there was a new peak detected in the cell whose retention time was shorter (3.42 min) than that of quercetin (4.65 min). This phenomenon suggested that quercetin might be transported into the neurons and then metabolized quickly to some derivative. Kaempferol could be transported into the neurons in a concentration- and time-dependent manner when the neurons were incubated with the culture medium containing kaempferol at the high dose. There was an apparent correlation between the concentrations of kaempferol in the medium and in the cell, indicating that the uptake of kaempferol in the cell increased along with its dose (10 ug/mL). However, there was a negative correlation between the concentrations of quercetin in the medium and in the cell. The results suggested that kaempferol and quercetin were disposed by the neurons at different way, and this might be an important factor for their different effects on primary cultured cortical cells. Metabolism / Metabolites To elucidate the metabolism of hispidulin in the large intestine, its biotransformation by the pig caecal microflora was studied. In addition, the efficiency of the pig caecal microflora to degrade galangin (3,5,7-trihydroxyflavone), kaempferol (3,5,7,4?-tetrahydroxyflavone), apigenin (5,7,4?-trihydroxyflavone), and luteolin (5,7,3?,4?- tetrahydroxyflavone) was investigated. Identification of the formed metabolites was performed by high-performance liquid chromatography (HPLC)-diode array detection, HPLC-electrospray ionization-tandem mass spectrometry, and high-resolution gas chromatography-mass spectrometry. The caecal microflora transformed ... kaempferol to 4-hydroxyphenylacetic acid, phloroglucinol, and 4-methylphenol; ... To elucidate to what extent different hydroxylation patterns on the B-ring influence the degradation degree of flavonoids, the conversions of galangin and kaempferol as well as that of apigenin and luteolin were compared with those of quercetin (3,5,7,3?, 4?-pentahydroxyflavone) and chrysin (5.7-dihydroxyflavone), respectively. Regardless of the flavonoid subclass, the presence of a hydroxy group at the 4?-position seems to be a prerequisite for fast breakdown. An additional hydroxy group at the B-ring did not affect the degradation degree. The metabolism of the flavonoids quercetin and kaempferol by rat hepatocytes was investigated using liquid chromatography coupled with electrospray mass spectrometry (LC-ESI MS). Quercetin and kaempferol were extensively metabolized (98.8 +/- 0.1% and 81.0 +/- 5.1% respectively, n = 4), with four glucuronides of quercetin and two of kaempferol being detected after incubation. The glucuronides of quercetin and kaempferol formed upon incubation with rat hepatocytes were identified as the same ones formed after incubation with the UDP-glucuronosyltransferase isoform UGT1A9. In addition, plasma samples from human volunteers taken after consumption of capsules of Ginkgo biloba, a plant rich in flavonoid glycosides, were analysed by LC-MS for the presence of flavonoid glucuronides and flavonoid glycosides. Reported is evidence for the presence of flavonoid glycosides in samples of plasma. The results suggest that UGT1A9 is a key UDP-glucuronosyltransferase isoform for the metabolism of flavonoids, and that absorption of intact flavonoid glycosides is possible. Kaempferol is a flavonoid widely distributed in edible plants and has been shown to be genotoxic to V79 cells in the absence of external metabolizing systems. The presence of an external metabolizing system, such as rat liver homogenates (S9 mix), leads to an increase in its genotoxicity, which is attributed to its biotransformation to the more genotoxic flavonoid quercetin, via the cytochrome P450 (CYP) mono-oxygenase system. ... Kaempferol has known human metabolites that include Kaempferol-3-glucuronide and (2S,3S,4S,5R)-6-[3,5-Dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid. Kaempferol is a known human metabolite of galangin and kaempferide. Biological Half-Life Ten adult volunteers with an average age 28 years were given a single oral dose of six tablets of Ginkgo biloba extract. ... The absorption half life was 1.51 hr and elimination half-life was 1.56 hr. |
| Toxicity/Toxicokinetics |
Interactions It has been reported that tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A, and kaempferol is an inhibitor of P-gp and CYP3A. Hence, it could be expected that kaempferol would affect the pharmacokinetics of tamoxifen. Thus, tamoxifen was administered orally (10 mg/kg) without or with oral kaempferol (2.5 and 10 mg/kg). In the presence of kaempferol, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of tamoxifen was significantly greater, C(max) was significantly higher and F was considerably greater than those without kaempferol. The enhanced bioavailability of oral tamoxifen by oral kaempferol could have been due to an inhibition of CYP3A and P-gp by kaempferol. The presence of kaempferol did not alter the pharmacokinetic parameters of a metabolite of tamoxifen, 4-hydroxytamoxifen. This could have been because the contribution of CYP3A to the formation of 4-hydroxytamoxifen is not considerable in rats. This study was to investigate the effect of kaempferol on the pharmacokinetics of etoposide after oral or intravenous administration of etoposide in rats. The oral (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30 min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased the area under the plasma concentration time curve (AUC) and the peak concentration (C(max)) of the oral etoposide. Kaempferol decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F) of oral etoposide, while there was no significant change in the terminal halflife (t(1/2)), the elimination rate constant (K(el)) and the time to reach the peak concentration (T(max)) of etoposide in the presense of kaempferol. Consequently, the absolute bioavailability (AB%) of oral etoposide with kaempferol was significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the control group. Compared to the intravenous control group, the presence of kaempferol enhanced the AUC of intravenously administered etoposide, however, only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of etoposide. The enhanced bioavailability of oral etoposide by kaempferol could have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P-gp) in the intestinal or decreased total body clearance in the liver by kaempferol. The dosage regimen of etoposide should be taken into consideration for potential drug interaction when combined with kaempferol or dietary supplements containing kaempferol in patients. Twenty male SD rats, weighing 220-260 g, were distributed randomly into 4 groups. The animals were fasted, but allowed free access to water for 12 hr before the administration of drugs. Nifedipine dissolved in corn oil was administered via gastric intubation to the rats in control group at a dose of 10 mg/kg. Kaempferol was administered orally to the other three groups with dose of 5, 10, 15 mg/kg, respectively, followed by oral administration of nifedipine 10 mg/kg. Blood samples were collected through tail vein in heparinized plastic microcentrifuge tubes before and after drug administration. The plasma concentration of NFP was monitored with reversed phase high-performance liquid chromatography (RP-HPLC). Nimodipine was used as the internal standard. Statistical data evaluation was performed with Student's t-test and one-way analysis of variances. The maximal plasma concentration (C(max)) of the three treated groups were 0.51, 0.70 and 0.81 microg/ml, respectively. The area under the concentration-time curve (AUC(0-8)) were 1.81, 2.83 and 3.63 ug/(hr.mL(-1)), respectively. The C(max), AUC(0-8) and the mean retention time (MRT(0-8)) of nifedipine were significantly increased by simultaneous oral treatment with kaempferol (P<0.01). On the other hand, there were no significant differences in the mean peak value time in plasma (T(max)) and the elimination half-life (t1/2(ke)) between the control and the treated groups. The concomitant oral use of kaempferol with nifedipine may influence the pharmacokinetic parameters of nifedipine in rats, which suggests that kaempferol might reduce the first-pass metabolism of nifedipine. Quercetin, kaempferol and biapigenin significantly reduced neuronal death caused by 100 uM kainate plus 100 uM N-methyl-D-aspartate. The observed neuroprotection was correlated with prevention of delayed calcium deregulation and with the maintenance of mitochondrial transmembrane electric potential. The three compounds were able to reduce mitochondrial lipid peroxidation and loss of mitochondrial transmembrane electric potential caused by oxidative stress induced by ADP plus iron. ... the results suggest that the neuroprotective action induced by quercetin and kaempferol are mainly mediated by antioxidant effects ... Kaempferol (Kempferol; Robigenin) (up to 100 μM in vitro) showed minimal toxicity to normal human ovarian epithelial cells [1] Kaempferol (Kempferol; Robigenin) (up to 80 mg/kg/day, oral) did not cause significant weight loss, hepatotoxicity, or nephrotoxicity in mice (serum ALT, AST, BUN, and creatinine levels were within normal range) [4] |
| References |
[1]. Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability. Int J Nanomedicine. 2012; 7: 3951-3959. [2]. Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway. Food Chem. 2011 September 15; 128(2): 513-519. [3]. Protective effects of Kaempferol against cardiac sinus node dysfunction via CaMKII deoxidization. Anat Cell Biol. 2015 Dec;48(4):235-43. [4]. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma. Int J Mol Sci. 2015 Dec 16;16(12):29980-95. |
| Additional Infomation |
Kaempferol is a tetrahydroxyflavone in which the four hydroxy groups are located at positions 3, 5, 7 and 4'. Acting as an antioxidant by reducing oxidative stress, it is currently under consideration as a possible cancer treatment. It has a role as an antibacterial agent, a plant metabolite, a human xenobiotic metabolite, a human urinary metabolite, a human blood serum metabolite and a geroprotector. It is a member of flavonols, a 7-hydroxyflavonol and a tetrahydroxyflavone. It is a conjugate acid of a kaempferol oxoanion. Kaempferol has been reported in Hydrangea serrata, Caragana frutex, and other organisms with data available. Kaempferol is a natural flavonoid which has been isolated from Delphinium, Witch-hazel, grapefruit, and other plant sources. Kaempferol is a yellow crystalline solid with a melting point of 276-278 degree centigrade. It is slightly soluble in water, and well soluble in hot ethanol and diethyl ether. Kaempferol is a metabolite found in or produced by Saccharomyces cerevisiae. See also: Cannabis sativa subsp. indica top (part of); Tussilago farfara flower (part of). Mechanism of Action Pure kaempferol and a number of related flavonoids were examined as MAOIs in-vitro. Kaempferol, apigenin and chrysin proved to be potent monoamine oxidase (MAO) inhibitors (MAOI)s, but produced more pronounced inhibition of MAO-A than MAO-B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO-A were 7 x 10(-7), 1 x 10(-6) and 2 x 10(-6) M, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex-vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Kaempferol was shown to protect against N-methyl-D-aspartate-induced neuronal toxicity in-vitro in rat cortical cultures, but did not prevent DSP-4-induced noradrenergic neurotoxicity in an in-vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid-peroxidation assay. This data indicates that the MAO-inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability. Kaempferol is a dietary flavonoid that is thought to function as a selective estrogen receptor modulator. ... This study ... established that kaempferol also functions as an inverse agonist for estrogen-related receptors alpha and gamma (ERRalpha and ERRgamma). ... Kaempferol binds to ERRalpha and ERRgamma and blocks their interaction with coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Kaempferol also suppressed the expressions of ERR-target genes pyruvate dehydrogenase kinase 2 and 4 (PDK2 and PDK4). This evidence suggests that kaempferol may exert some of its biological effect through both estrogen receptors and estrogen-related receptors. Therapeutic Uses /EXPL/ Despite recent advances in understanding molecular mechanisms involved in glioblastoma progression, the prognosis of the most malignant brain tumor continues to be dismal. Because the flavonoid kaempferol is known to suppress growth of a number of human malignancies, we investigated the effect of kaempferol on human glioblastoma cells. Kaempferol induced apoptosis in glioma cells by elevating intracellular oxidative stress. Heightened oxidative stress was characterized by an increased generation of reactive oxygen species (ROS) accompanied by a decrease in oxidant-scavenging agents such as superoxide dismutase (SOD-1) and thioredoxin (TRX-1). Knockdown of SOD-1 and TRX-1 expression by small interfering RNA (siRNA) increased ROS generation and sensitivity of glioma cells to kaempferol-induced apoptosis. Signs of apoptosis included decreased expression of Bcl-2 and altered mitochondrial membrane potential with elevated active caspase-3 and cleaved poly(ADP-ribose) polymerase expression. Plasma membrane potential and membrane fluidity were altered in kaempferol-treated cells. Kaempferol suppressed the expression of proinflammatory cytokine interleukin-6 and chemokines interleukin-8, monocyte chemoattractant protein-1, and regulated on activation, normal T-cell expressed and secreted. Kaempferol inhibited glioma cell migration in a ROS-dependent manner. Importantly, kaempferol potentiated the toxic effect of chemotherapeutic agent doxorubicin by amplifying ROS toxicity and decreasing the efflux of doxorubicin. Because the toxic effect of both kaempferol and doxorubicin was amplified when used in combination, this study raises the possibility of combinatorial therapy whose basis constitutes enhancing redox perturbation as a strategy to kill glioma cells. /EXPL/ Kaempferol is one of the most important constituents in ginkgo flavonoids. Recent studies indicate kaempferol may have antitumor activities. The objective of this study was to determine the effect and mechanisms of kaempferol on pancreatic cancer cell proliferation and apoptosis. Pancreatic cancer cell lines MIA PaCa-2 and Panc-1 were treated with kaempferol, and the inhibitory effects of kaempferol on pancreatic cancer cell proliferation were examined by direct cell counting, 3H-thymidine incorporation, and MTS assay. Lactate dehydrogenase release from cells was determined as an index of cytotoxicity. Apoptosis was analyzed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay. Upon the treatment with 70 microm kaempferol for 4 days, MIA PaCa-2 cell proliferation was significantly inhibited by 79% and 45.7% as determined by direct cell counting and MTS assay, respectively, compared with control cells (P < 0.05). Similarly, the treatment with kaempferol significantly inhibited Panc-1 cell proliferation. Kaempferol treatment also significantly reduced 3H-thymidine incorporation in both MIA PaCa-2 and Panc-1 cells. Combination treatment of low concentrations of kaempferol and 5-fluorouracil showed an additive effect on the inhibition of MIA PaCa-2 cell proliferation. Furthermore, kaempferol had significantly less cytotoxicity than 5-fluorouracil in normal human pancreatic ductal epithelial cells (P = 0.029). In both MIA PaCa-2 and Panc-1 cells, apoptotic cell population was increased when treated with kaempferol in a concentration-dependent manner. CONCLUSIONS: Ginkgo biloba extract kaempferol effectively inhibits pancreatic cancer cell proliferation and induces cancer cell apoptosis, which may sensitize pancreatic tumor cells to chemotherapy. Kaempferol may have clinical applications as adjuvant therapy in the treatment of pancreatic cancer. /EXPL/ Dietary flavonols have been found to possess preventive and therapeutic potential against several kinds of cancers. This study is conducted to investigate the anti-proliferation effects of kaempferol, a major component of food flavonols, against colon cancer cells. In the human HCT116 colon cancer cell line, kaempferol induced p53-dependent growth inhibition and apoptosis. Furthermore, kaempferol was found to induce cytochrome c release from mitochondria and activate caspase-3 cleavage. The Bcl-2 family proteins including PUMA were involved in this process. Kaempferol also induced ATM and H2AX phosphorylation in HCT116 cells, inhibition of ATM by a chemical inhibitor resulted in abrogation of the downstream apoptotic cascades. These findings suggest kaempferol could be a potent candidate for colorectal cancer management. /EXPL/ ... Treatment of the chronic myelogenous leukemia cell line K562 and promyelocitic human leukemia U937 with 50 microM kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase-3, and -9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance of K562 cells to kaempferol. Inhibition of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. ... Oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2, release of cytochrome c, caspase-3 activation, and cell death. /EXPL/ 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. Kaempferol (Kempferol; Robigenin) is a natural flavonoid widely distributed in fruits (grapes, apples), vegetables (onions, broccoli), and herbs (tea, ginkgo biloba) [1][2][3][4] Kaempferol (Kempferol; Robigenin) exerts anti-ovarian cancer effects via inducing cell cycle arrest and apoptosis, with nanoparticles enhancing its selective cytotoxicity to cancer cells [1] Kaempferol (Kempferol; Robigenin) protects cardiac sinus node function by reducing CaMKII oxidation and inhibiting mitochondrial-dependent apoptosis [3] Kaempferol (Kempferol; Robigenin) alleviates allergic asthma-related airway remodeling by inhibiting airway smooth muscle proliferation and suppressing pro-inflammatory cytokine production [4] Kaempferol (Kempferol; Robigenin) activates the intrinsic apoptotic pathway in ovarian cancer cells through upregulating p53 and Bax, downregulating Bcl-2, and activating caspases [2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (6.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (6.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2 mg/mL (6.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 5 mg/mL (17.47 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4937 mL | 17.4685 mL | 34.9369 mL | |
| 5 mM | 0.6987 mL | 3.4937 mL | 6.9874 mL | |
| 10 mM | 0.3494 mL | 1.7468 mL | 3.4937 mL |