kaempferide and kaempferol

Propolis, a compound produced by honeybees, has long been used in food and beverages to improve health and prevent diseases. We previously reported that the ethanol extracts of Brazilian green propolis and its constituents artepillin C, kaempferide, and kaempferol mitigate oxidative stress-induced cell death via oxytosis/ferroptosis. Here, we investigated the potential of Brazilian green propolis and its constituents to protect against endoplasmic reticulum stress in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis, artepillin C, and kaempferol attenuated tunicamycin-induced unfolded protein response and cell death. Interestingly, artepillin C inhibited both tunicamycin-induced protein aggregation in HT22 cells and the spontaneous protein aggregation of mutant canine superoxide dismutase 1 (E40K-SOD1-EGFP) in Neuro2a cells. These findings indicate that in addition to oxidative stress, the ethanol extracts of Brazilian green propolis help prevent endoplasmic reticulum stress-related neuronal cell death, which is proposedly involved in several neurodegenerative diseases. Moreover, artepillin C, a major constituent of Brazilian green propolis, may exhibit chemical chaperone-like properties.

Topics: Animals; Brazil; Cell Death; Cell Line; Cell Survival; Cinnamates; Coumaric Acids; eIF-2 Kinase; Endoplasmic Reticulum Stress; Ethanol; Eukaryotic Initiation Factor-2; Flavonoids; Hippocampus; Kaempferols; Membrane Proteins; Mice; Oxidative Stress; Phenylpropionates; Propolis; Protective Agents; Protein Aggregates; Protein Serine-Threonine Kinases; Trichothecenes; Tunicamycin

Topics: Carcinoma, Hepatocellular; Fatty Liver; Hep G2 Cells; Humans; Kaempferols; Lipogenesis; Liver Neoplasms; Oleic Acid; Oxidative Stress; Signal Transduction

Propolis is a sticky dark-colored substance produced by honey bees and comprises resin, balsam, wax, essential and aromatic oils, pollen, and several other substances; it is used in food and beverages to improve health and prevent diseases. We studied the neuroprotective effects of extracts of Brazilian green propolis in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis had a more potent preventive effect on oxidative stress-induced cell death, oxytosis/ferroptosis, in HT22 cells than water extracts of Brazilian green propolis, whereas it did not protect against anticancer drug-induced apoptotic cell death. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. The flavonoid derivatives kaempferide and kaempferol are antioxidants with radical-scavenging abilities that additionally induce antioxidant response element-mediated transcriptional activity, suggesting that upregulation of endogenous antioxidant defense protects against oxidative stress. In contrast, artepillin C attenuated reactive oxygen species production; however, it did not induce antioxidant response element activation. These findings indicate that the ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases.

Topics: Animals; Apoptosis; Brazil; Calcium; Cell Line; Glutamic Acid; Glutathione; Heme Oxygenase-1; Hippocampus; Kaempferols; Mice; Neuroprotective Agents; Oxidative Stress; Phenylpropionates; Propolis; Reactive Oxygen Species; Superoxides

Mutation in Cu/Zn superoxide dismutase (SOD1) at position 85 from glycine to arginine was found to be a prominent cause of aggregation characterized by an increased content of β-sheets in familial amyotrophic lateral sclerosis (fALS). Various literatures reported that natural polyphenols could act as a β-sheet breaker and therefore, treated as a potential therapeutics against various aggregated proteins involved in neurodegenerative disorders. Through computational perspective, molecular docking, quantum chemical studies, and discrete molecular dynamics were implemented to study the binding and structural effect of natural polyphenols, kaempferol, and kaempferide on mutant SOD1. Kaempferol exhibited significant binding and greater residual energy contribution with mutant SOD1 than kaempferide. More interestingly, kaempferol was found to reduce the β-sheet content augmenting the mutant conformational stability and flexibility relative to that of kaempferide. Hence, the inhibition of mutant SOD1 aggregation by kaempferol was explored, thereby suggesting kaempferol could act as a drug candidate for the design of the natural therapeutics against fALS. © 2018 BioFactors, 44(5):431-442, 2018.

Topics: Amyotrophic Lateral Sclerosis; Humans; Kaempferols; Molecular Docking Simulation; Molecular Dynamics Simulation; Mutant Proteins; Mutation; Protein Aggregation, Pathological; Protein Binding; Quantum Theory; Superoxide Dismutase-1

Tea (Camellia sinensis) is an important commercial crop, in which the high content of flavonoids provides health benefits. A flavonoid glycosyltransferase (CsUGT73A20), belonging to cluster IIIa, was isolated from tea plant. The recombinant CsUGT73A20 in Escherichia coli exhibited a broad substrate tolerance toward multiple flavonoids. Among them, kaempferol was the optimal substrate compared to quercetin, myricetin, naringenin, apigenin, and kaempferide. However, no product was detected when UDP-galactose was used as the sugar donor. The reaction assay indicated that rCsUGT73A20 performed multisite glycosidation toward flavonol compounds, mainly forming 3-O-glucoside and 7-O-glucoside in vitro. The biochemical characterization analysis of CsUGT73A20 showed more K7G product accumulated at pH 8.0, but K3G was the main product at pH 9.0. Kinetic analysis demonstrated that high pH repressed the glycosylation reaction at the 7-OH site in vitro. Besides, the content of five flavonol-glucosides was increased in CsUGT73A20-overexpressing tobaccos (Nicotiana tabacum).

Topics: Camellia sinensis; Enzyme Stability; Flavanones; Flavonoids; Glycosyltransferases; Kaempferols; Kinetics; Plant Proteins; Substrate Specificity

Flavonoids are polyphenolic compounds required in the fertilization process in many, if not all, plants. However, the exact biological mechanism(s) and the interacting proteins are unknown. To determine the characteristics important in activating or inhibiting the pollination sequence, a structure-activity relationship analysis of natural and synthetic flavonols was conducted. Flavonol analogues were synthesized through a modified "one-pot" procedure that utilized a Baker-Venkataraman type rearrangement and a Suzuki-Miyaura cross-coupling of a halo-flavonol with an organotrifluoroborate. Of the flavonols tested, kaempferol was the only compound to act as a full agonist. The other smaller, less sterically hindered flavonols (galangin, kaempferide, and 4'-methyl flavonol) acted as partial agonists. Larger more hydrophobic flavonol analogues (3'- and 4'-benzoyl, 3'- and 4'-phenyl, and 3'- and 4'-iodo flavonols) had minimal or no agonist activity. Competition assays between kaempferol and these minimally activating flavonols showed that these analogues inhibited the action of kaempferol in a manner consistent with noncompetitive antagonism. The results suggest that steric hindrance is the most important factor in determining a good agonist. Hydrogen bonding also had a positive effect as long as the substituent did not cause any steric hindrance.

Topics: Chemistry Techniques, Synthetic; Flavonoids; Flavonols; Germination; Hydrogen Bonding; Kaempferols; Petunia; Plants, Genetically Modified; Pollen; Structure-Activity Relationship

Methylation of flavonoids appears to be a simple and effective way to improve metabolic resistance and transport of flavonoids. Serum albumins are major soluble proteins serving as transport proteins for many exogenous compounds. This work in here mainly concerns about the effect of methylation of flavonoids on the affinity for human serum albumin (HSA) and ovalbumin. One isoflavone (genistein) and one flavonol (kaempferol) and their monomethylated derivatives at position 4' (biochanin A and kaempferide) were studied for their affinities for ovalbumin and HSA. The methylation of flavonoids significantly affects the binding process. In general, the methylation of flavonoids improved the affinities for proteins by 2-16 times. This result supports that the methylation of genistein and kaempferol enhanced the transporting ability, which leads to facilitated absorption and greatly increased bioavailability. The methylation increases the hydrophobicity of genistein and kaempferol, and the hydrophobic interaction plays an important role in binding flavonoids to HSA and ovoalbumin.

Topics: Biological Availability; Biological Transport; Genistein; Humans; Hydrophobic and Hydrophilic Interactions; Intestinal Absorption; Kaempferols; Methylation; Ovalbumin; Protein Binding; Serum Albumin

Topics: Binding Sites; Glycosides; Kaempferols; Spectrometry, Mass, Electrospray Ionization

Quantitative parameters for interaction of flavonoids-the naturally occurring antioxidants, with solvents and surfactants are determined using UV-visible absorption spectroscopy. The availability of flavonoids; kaempferol, apigenin, kaempferide and rhamnetin in micelles of sodium dodecyl sulfate (SDS) is reflected in terms of partition coefficient, K(c). Thermodynamic calculations show that the process of transfer of flavonoid molecules to anionic micelles of SDS is energy efficient. A distortion in flavonoid's morphology occurs in case of kaempferol and apigenin in surfactant and water, exhibited in terms of a new band in the UV region of electronic spectra of these flavonoids. The partition coefficients of structurally related flavonoids are correlated with their antioxidant activities.

Topics: Antioxidants; Apigenin; Flavonoids; Kaempferols; Methanol; Micelles; Quercetin; Sodium Dodecyl Sulfate; Solubility; Solutions; Spectrophotometry, Ultraviolet; Spectrum Analysis; Temperature; Thermodynamics; Water

Four new flavonol gycosides: kaempferide 3-O-beta-xylosyl (1-->2)-beta-glucoside, kaempferol 3-O-alpha-rhamnoside-7,4'-di-O-beta-galactoside, kaempferol 3,7,4'-tri-O-beta-glucoside and quercetin 3-O-[alpha-rhamnosyl (1-->6)] [beta-glucosyl (1-->2)]-beta-glucoside-7-O-alpha-rhamnoside, were characterized from a methanolic leaf extract of Warburgia ugandensis. The known flavonols: kaempferol, kaempferol 3-rhamnoside, kaempferol 3-rutinoside, myricetin, quercetin 3-rhamnoside, kaempferol 3-arabinoside, quercetin 3-glucoside, quercetin, kaempferol 3-rhamnoside-4'-galactoside, myricetin 3-galactoside and kaempferol 3-glucoside were also isolated. Structures were established by spectroscopic and chemical methods and by comparison with authentic samples.

Topics: Flavonoids; Flavonols; Glycosides; Kaempferols; Magnetic Resonance Spectroscopy; Plant Leaves; Plants, Medicinal; Quercetin; Spectrometry, Mass, Fast Atom Bombardment

There is very limited information on cytochrome P450 (P450)-mediated oxidative metabolism of dietary flavonoids in humans. In this study, we used human liver microsomes and recombinant P450 isoforms to examine the metabolism of two flavonols, galangin and kaempferide, and one flavone, chrysin. Both galangin and kaempferide, but not chrysin, were oxidized by human liver microsomes to kaempferol, with K(m) values of 9.5 and 17.8 microM, respectively. These oxidations were catalyzed mainly by CYP1A2 but also by CYP2C9. Consistent with these observations, the human liver microsomal metabolism of galangin and kaempferide were inhibited by the P450 inhibitors furafylline and sulfaphenazole. In addition, CYP1A1, although less efficient, was also able to oxidize the two flavonols. Thus, dietary flavonols are likely to undergo oxidative metabolism mainly in the liver but also extrahepatically.

Topics: Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Flavonoids; Humans; Isoenzymes; Kaempferols; Microsomes, Liver; Mutagens; Oxidation-Reduction; Quercetin; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Trisaccharides

Starting from the interaction of galangin (3,5,7-trihydroxyflavone) with a cytosolic nucleotide-binding domain of P-glycoprotein, a series of flavonol derivatives was synthesized and tested for their binding affinity towards the same target. The 5,7-dihydroxy-4'-iodoflavonol and 5,7-dihydroxy-4'-n-octylflavonol derivatives displayed much higher binding affinities, with respective increases of 6- and 93-fold as compared to galangin.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Binding Sites; Chalcone; Drug Resistance, Multiple; Flavonoids; Flavonols; Fluorescence; Kaempferols; Molecular Structure; Protein Binding; Protein Structure, Tertiary; Quercetin; Recombinant Proteins; Thermodynamics; Tryptophan

The EtOH extract of Koelreuteria henryi was investigated in a search for natural products with potential protein-tryrosine kinase (PTK) inhibitory activity. The PTK inhibitory activity of the crude fractions was determined by measuring their inhibition of p56lck partially purified from bovine thymus using angiotensin I as a substrate. Analysis of those fractions that exhibited significant activity led to the isolation of kaempferol and quercetin, in addition to two kaempferol glycosides, kaempferol-O3-alpha-rhamnopyranoside [1] and kaempferol-O3-alpha-arabinopyranoside [2]. This study represents the first report on the isolation of flavonols and their PTK inhibitory activities from the genus Koelreuteria. Eight other flavonoids were also examined to study the role of the hydroxy groups on the B ring on PTK inhibitory activity.

Topics: Animals; Cattle; Flavonoids; Kaempferols; Magnetic Resonance Spectroscopy; Plant Extracts; Plants; Protein-Tyrosine Kinases; Quercetin