Intake Of Kaempferol Research Articles

Kaempferol Reduces Cardiopulmonary Load and Muscular Damage in Repeated 400‐m Sprints: A Double‐Blind, Randomized, Placebo‐Controlled Trial

ABSTRACTPlants exposed to hypoxic conditions have been suggested to produce more biologically active phytochemicals than those exposed to normal oxygen levels. Previously, we investigated 314 highland crop species and showed that the flavonoid kaempferol extracted from a highland quinoa grain markedly increased mitochondrial metabolism and ATP production in a hypoxic environment in vitro. Thus, we hypothesized that kaempferol would be effective during exercise under harsh conditions, in which anaerobic metabolism occurs. This study adopted a double‐blind, placebo‐controlled, crossover design to investigate the effect of a single oral dose of kaempferol (10 mg) on the athletic performance‐related indicators of 13 male university athletes (20.8 ± 0.7 years) who performed two consecutive 400‐m runs with the shortest 90‐min interval assuming qualifying and main races. Although no significant differences were observed in the 400‐m race times between the placebo and kaempferol groups, kaempferol intake markedly reduced the respiratory and heart rates during the second run (p < 0.05). In addition, kaempferol intake reduced the levels of muscle damage markers, myoglobin, and aspartate transaminase (p < 0.05). A single oral dose of kaempferol reduced the cardiopulmonary burden and muscle damage in individuals participating in 400‐m runs. Kaempferol may be a useful supplement for relieving the physical load, particularly in individuals performing strenuous exercises with high oxygen demand.Trial Registration: UMIN Clinical Trials Registry in Japan: UMIN000049588

Interaction of bioactive kaempferol with HMGB1: Investigation by multi-spectroscopic and molecular simulation methods

Chronic and persistent inflammation associated with excessive high mobility group protein 1 (HMGB1) is a risk factor for various diseases. Dietary intake of kaempferol has been proven to be effective in reducing HMGB1 levels and the degree of inflammation, but the structural mechanism remains unclear. In this context, we first investigated the interaction between bioactive kaempferol and HMGB1 using multi-spectroscopic and molecular simulation techniques. The surface plasmon resonance (SPR) data indicated that kaempferol binds directly to HMGB1 with a Kd value of 2.89 × 10−5 M. Binding of kaempferol with HMGB1 led to the intrinsic fluorescence quenching and modest secondary structure change of HMGB1 supported by fluorescence spectrometry and circular dichroism (CD). Using dynamic light scattering (DLS), it was found that kaempferol induced the aggregation of HMGB1 protein complex to form larger particles. On HMGB1-activated RAW264.7 cells, kaempferol co-incubation exhibited a remarkable inhibitory effect on nitric oxide (NO) release with an IC50 value of 5.02 μM, which was lower than that of quercetin. In silico, kaempferol binds to HMGB1 mainly through hydrogen bonds and hydrophobic forces. Collectively, our study showed kaempferol as a potential HMGB1 inhibitor, mainly acting by direct binding to HMGB1 and inducing its conformational changes, which provides clues for the treatment of chronic inflammation by kaempferol.

Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities.

Previous research has examined the association between cognition and flavonoids: bioactives found in foods, known to possess anti-inflammatory and antioxidant properties. We extend this research by investigating associations of dietary intakes of total flavonols and constituents (kaempferol, quercetin, myricetin, and isorhamnetin) on the change in cognitive performance in global cognition, episodic memory, semantic memory, visuospatial ability, perceptual speed, and working memory. The study was conducted using 961 participants (aged 60-100 years) of the Rush Memory and Aging Project, a prospective cohort of community-dwelling Chicagoans who were followed for an average of 6.9 years. Diet was assessed using a validated semiquantitative food frequency questionnaire. Cognitive performance was assessed annually with a battery of 19 standardized tests. Flavonol intake was analyzed as a continuous variable using linear mixed-effects models. Cognitive domain scores were regressed on baseline calorie-adjusted flavonol variables. Higher dietary intakes of total flavonols and flavonol constituents were associated with a slower rate of decline in global cognition and multiple cognitive domains. In continuous models adjusted for age, sex, education, APOE ɛ4, late-life cognitive activity, physical activity, and smoking, total flavonol intake was associated with slower decline in global cognition β estimate = 0.004 (95% CI 0.001-0.006), episodic memory β = 0.004 (95% CI 0.002-0.006), semantic memory β = 0.003 (95% CI 0.001-0.007), perceptual speed β = 0.003 (95% CI 0.001-0.004), and working memory β = 0.003 (95% CI 0.001-0.005) and marginally associated with visuospatial ability β = 0.001 (95% CI -0.001 to 0.003). Analyses of individual flavonol constituents demonstrated that intakes of kaempferol and quercetin were associated with slower global cognitive decline (β = 0.01 [95% CI 0.006-0.02] and β = 0.004 [95% CI 0.0005-0.007]), respectively. Myricetin and isorhamnetin were not associated with global cognition. Results suggest that dietary intakes of total flavonols and several flavonol constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.

Dietary Isorhamnetin Intake Is Inversely Associated with Coronary Artery Disease Occurrence in Polish Adults.

The role of antioxidative agents in coronary artery disease (CAD) has been investigated, but the analysis of specific flavonols intake in Polish adults requires validated tools. The aim of this study was to estimate the dietary intake of flavonols in CAD patients by creating a food frequency questionnaire (FFQ) dedicated for this purpose in Polish adults. The FFQ included 140 products from 12 food groups. The study involved 103 adult respondents (43 CAD patients and 60 healthy controls). Mean daily intakes of total flavonols, quercetin, kaempferol, myricetin and isorhamnetin were calculated as absolute values and quartiles. Mean daily intakes of 12 main food categories and 27 subcategories were calculated as portions and quartiles. The validity test revealed high correlation for total flavonols, kaempferol, myricetin and isorhamnetin and moderate for quercetin. In the reproducibility analysis, the correlation was high for total flavonols, quercetin, kaempferol and myricetin, moderate for isorhamnetin and high for all 12 categories and 25 out of 27 subcategories of the tested food groups. The application of the FFQ in healthy adults and CAD patients revealed that dietary intakes of total flavonols and proportional intakes of kaempferol and isorhamnetin in Polish adults and CAD patients are higher than in most other European countries, while the proportional intakes of quercetin and myricetin are lower than in most European countries. The comparison between CAD patients and the healthy controls revealed significant differences in dietary isorhamnetin intake (p = 0.002). The results suggest that dietary isorhamnetin could have a potential role in CAD prevention.

Food frequency questionnaire is a valid assessment tool of quercetin and kaempferol intake in Iranian breast cancer patients according to plasma biomarkers

In epidemiological and clinical studies, the most common nutritional tool to assess dietary flavonol intake is the food frequency questionnaire (FFQ), which needs to contain a detailed list of plant-based foods and be previously validated. Our study aimed to assess the accuracy of dietary flavonol (quercetin, kaempferol, and isorhamnetin) intake from a food frequency questionnaire (FFQ) compared to fasting plasma flavonol concentrations, as biomarkers of exposure, in breast cancer patients. In a consecutive case series, newly diagnosed patients with breast cancer (n = 140) were recruited at Nour-Nejat Hospital, Tabriz, Iran. Flavonol intake was assessed using a validated FFQ. Plasma flavonol concentrations were measured using high-performance liquid chromatography-ultraviolet detection. The accuracy of dietary status was evaluated using a receiver operating characteristic (ROC) and area under the ROC curve (AUC). Dietary status was shown in dichotomous using ROC-cutoff point. The plasma concentrations of quercetin were moderately correlated with dietary intake of quercetin (Spearman's correlation coefficient (rs) = 0.188, P < .05; rpartial= 0.330, P < .01) and plasma concentrations of isorhamnetin (rs = 0.337, P < .001). A linear correlation between dietary levels and plasma concentrations of kaempferol was attained (rpartial = 0.240, P < .05). Using a ROC-cutoff of 61.9 nmol/L for plasma quercetin (test reference), we were able to differentiate between lower and higher consumers of quercetin with an AUCROC-based reference =0.65 (P < .01, sensitivity = 61.8%, and specificity = 60.0%). Using a plasma kaempferol concentration of 60.1 nmol/L (ROC-cutoff), it was possible to detect significant differences between higher and lower intakes of kaempferol (AUCROC-based reference = 0.64, P < .05). The correlations and diagnostic performance with plasma concentrations could present a significant accuracy rate (validity), which seems acceptable for a nutritional questionnaire (FFQ) to assess intakes intake levels of quercetin and kaempferol. An improvement in the accuracy of the flavonol exposure can provide more precise relationship with health outcomes, which may increase their clinical significance.

Intake of selected bioactive compounds from plant food supplements containing fennel (Foeniculum vulgare) among Finnish consumers

The purpose of this study was to estimate the intake of selected bioactive compounds from fennel-containing plant food supplements (PFS) among Finnish consumers. The estimated average intake of estragole was 0.20mg/d, of trans-anethole 1.15mg/d, of rosmarinic acid 0.09mg/d, of p-coumaric acid 0.0068mg/d, of kaempferol 0.0034mg/d, of luteolin 0.0525μg/d, of quercetin 0.0246mg/d, of matairesinol 0.0066μg/d and of lignans 0.0412μg/d. The intakes of kaempferol, quercetin, luteolin, matairesinol and lignans from PFS were low in comparison with their dietary supply. The intake of estragole was usually moderate, but a heavy consumption of PFS may lead to a high intake of estragole. The intake of trans-anethole did not exceed the acceptable daily intake, but PFS should be taken into account when assessing the total exposure. To our knowledge, this study provided the first intake estimates of trans-anethole, p-coumaric acid and rosmarinic acid in human populations.

Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation

Kaempferol is a natural flavonoid found in many vegetables and fruits. Epidemiologic studies have described that Kaempferol intake could reduce risk of cancer, especially lung, gastric, pancreatic and ovarian cancers. Recent studies have shown that Kaempferol could also be beneficial to the body to defend against inflammation, and infection by bacteria and viruses; however, the molecular mechanism of its immunoregulatory function remains largely unknown. Through screening a small molecule library of traditional Chinese medicine (TCM), we identified that Kaempferol could enhance the suppressive function of regulatory T cells (Tregs). Kaempferol was found to increase FOXP3 expression level in Treg cells and prevent pathological symptoms of collagen-induced arthritis in a rat animal model. Kaempferol could also reduce PIM1-mediated FOXP3 phosphorylation at S422. Our study reveals a molecular mechanism that underlies the anti-inflammatory action of Kaempferol for the prevention and treatment of inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.

Dietary flavonol, flavone and catechin intake and risk of colorectal cancer in the Netherlands Cohort Study

Dietary flavonoids are hypothesized to be protective against colorectal cancer, yet findings have been inconsistent. We examined the association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints within the Netherlands Cohort Study (NLCS). In addition, we explored whether body mass index (BMI) may be an effect modifier of this association. The NLCS includes 120,852 men and women who were 55-69 years and completed a self-administered questionnaire at baseline in 1986. A case-cohort approach was used for data processing and analysis. After 13.3 years, 1,444 male and 1,041 female colorectal cancer cases were available for estimation of hazard ratios and 95% confidence intervals for quintiles of flavonoid intake. After adjustment for potential confounders, no association of total flavonol and flavone intake and total catechin intake with colorectal cancer endpoints was observed. Analyses stratified for BMI showed significant inverse trends in the association of total catechin intake, (+)-catechin intake and (-)-epicatechin intake with rectal cancer in men with a BMI>or=25 kg/m2 and in the association of total catechin intake and intake of kaempferol, myricetin and all individual catechins with colorectal cancer, in particular colon cancer, in women with a BMI<25 kg/m2. In conclusion, our findings generally do not support an association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints. Dietary catechin intake may be associated with a decreased rectal cancer risk in overweight men. Dietary flavonol and catechin intake may be associated with a decreased colorectal cancer risk in normal weight women.

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Flavonoids are antioxidant compounds found in plants, including fruits, vegetables and tea. No prior prospective studies have examined the association between intake of flavonoids in the flavonol and flavone subclasses and ovarian cancer risk. We analyzed the association between intake of 5 common dietary flavonoids and incidence of epithelial ovarian cancer among 66,940 women in the Nurses' Health Study. We calculated each participant's intake of myricetin, kaempferol, quercetin, luteolin and apigenin from dietary data collected at multiple time points, and used Cox proportional hazards regression to model the incidence rate ratio (RR) of ovarian cancer for each quintile of intake. Our analysis included 347 cases diagnosed between 1984 and 2002, and 950,347 person-years of follow-up. There was no clear association between total intake of the 5 flavonoids examined and incidence of ovarian cancer (RR = 0.75 for the highest versus lowest quintile, 95% confidence interval [CI] = 0.51-1.09). However, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake (RR = 0.60, 95% CI = 0.42-0.87; p-trend = 0.002), and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake (RR = 0.66, 95% CI = 0.49-0.91; p-trend = 0.01). There was evidence of an inverse association with consumption of tea (nonherbal) and broccoli, the primary contributors to kaempferol intake in our population. These data suggest that dietary intake of certain flavonoids may reduce ovarian cancer risk, although additional prospective studies are needed to further evaluate this association. If confirmed, these results would provide an important target for ovarian cancer prevention.

Dietary Intakes of Flavonols and Flavones and Coronary Heart Disease in US Women

Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.

Urinary excretion of kaempferol from common beans (Phaseolus vulgaris L.) in humans

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 hydrolysed flavonol was obtained after 2–8 h. 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 h 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.

Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain.

To investigate the relationship between gastric cancer and the intake of specific carotenoids (alpha-carotene, beta-carotene, lutein, and lycopene) and flavonoids (quercetin, kaempferol, myricetin, and luteolin) using new data on their concentration in foods. Case-control study carried out in Spain that included 354 cases of gastric cancer and 354 controls, matched by age, gender, area of residence and hospital. Usual food intake was assessed using a dietary history questionnaire. In a multivariate model adjusted for several dietary factors, no association was found between intake of any of the studied carotenoids and the risk of gastric cancer. The adjusted OR of gastric cancer for the highest quartile of total flavonoid intake versus the lowest quartile was 0.44 (95 percent confidence interval [CI] = 0.25-0.78; P for trend = 0.003). Kaempferol intake was found to be protective (OR = 0.48; CI = 0.26-0.88; P for trend = 0.04) comparing the highest versus the lowest quartile of intake. A trend toward lower risk of stomach cancer with higher intake of quercetin was also found. The results of this study support the hypothesis that the well-established protective effect of fruit and vegetables against gastric cancer could, in part, be due to the presence of flavonoids.