chrysin and naringenin

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Bone Density; Female; Flavanones; Flavonoids; Oxidative Stress; Rats

Three new biflavones, apigenin-(3',8″)-chrysin (

Topics: Antineoplastic Agents; Apigenin; Cell Death; Cell Line, Tumor; Flavanones; Flavones; Flavonoids; Humans; Magnetic Resonance Spectroscopy; Plant Extracts; Selaginellaceae

Topics: Animals; Bees; Diet, High-Fat; Disease Models, Animal; Flavanones; Flavonoids; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Pollen; Rutin; Schisandra

Phytochemicals are ubiquitous in naturally occurring dietary elements that exhibits diverse pharmacological properties over various pathological disorders, including cancer. Voltage gated K

Topics: Antineoplastic Agents, Phytogenic; Caffeic Acids; Cell Line, Tumor; Flavanones; Flavonoids; Gallic Acid; Guaiacol; Humans; Ion Transport; Male; Membrane Potentials; Patch-Clamp Techniques; PC-3 Cells; Phytochemicals; Potassium; Potassium Channels, Voltage-Gated

Herbaspirillum seropedicae is an associative, endophytic non-nodulating diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR-type transcriptional regulator, very similar to NodD proteins of rhizobia, was identified in its genome. This nodD-like gene, named fdeR, is divergently transcribed from an operon encoding enzymes involved in flavonoid degradation (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent manner. The intergenic region between fdeR and fdeA contains several generic LysR consensus sequences (T-N

Topics: Bacterial Proteins; Base Sequence; Biodegradation, Environmental; Flavanones; Flavonoids; Gene Expression Regulation, Bacterial; Herbaspirillum; Operon; Promoter Regions, Genetic; Rhizobium; Transcriptional Activation

Formation of plasmonic silver nanoparticles by flavonoid reduction was studied. Effects of the nature and the concentration of a flavonoid and a stabilizer, composition of the solution and the interaction time were revealed. It was found that quercetin, dihydroquercetin, rutin and morin produced an intense surface plasmon resonance band of silver nanoparticles at 415 nm which was linearly related to the concentration of a flavonoid, while chrysin, naringenin and naringin did not produce any remarkable changes. It was used for the spectrophotometric determination of the former four flavonoids with the detection limits of 0.03; 0.06; 0.09 and 0.1 μg mL(-1), respectively. The developed method was applied for the determination of flavonoids in biologically active food additives.

Topics: Flavanones; Flavonoids; Metal Nanoparticles; Quercetin; Rutin; Silver; Spectrophotometry

Reactive oxygen species play a role in a number of degenerative conditions including osteoporosis. Flavonoids as phyto-oestrogens exert physiological effects against oxidative stress diseases. We developed a retinoic acid-induced bone loss model of rats to assess whether flavonoids and alendronate as positive control have role against oxidative stress and mineral contents in osteoporosis in vivo.. Three-month-old female rats of the Y59 strain were given quercetin, chrysin, naringenin (100 mg kg(-1)) or alendronate (40 mg kg(-1), a positive control) immediately before retinoic acid treatment (80 mg kg(-1)) once daily for 14 days by a single intragastric (i.g.) application. In the second part of the study, we assessed the effect of those flavonoids on the skeletal system of healthy rats using single i.g. application on the respective flavonoids during 14 days. Twenty-four hours after the treatment, we analysed bone mineral density and the total content of bone calcium and phosphorus in the femur, the geometric and physical characteristics of thigh bones and lipid peroxidation and glutathione levels of liver and kidney cells.. All flavonoids improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash and calcium and phosphorus content induced by retinoic acid. Chrysin and quercetin showed promise as preventive agents. Flavonoids were superior to alendronate according to some criteria.. These results suggest that the dietary flavonoids could reduce retinoic acid-induced oxidative stress and bone loss and that flavonoids may be useful therapeutics for prevention of skeletal diseases.

Topics: Animals; Bone Density; Calcium; Disease Models, Animal; Female; Femur; Flavanones; Flavonoids; Lipid Peroxidation; Minerals; Osteoporosis; Oxidative Stress; Phosphorus; Quercetin; Rats; Tretinoin

Total phenolic content (TPC), total anthocyanin content (TAC), free and total ellagic acid content, sugars, minerals, and radical-scavenging activity were determined in nine berries harvested in Serbia. More than 30 phenolic compounds were identified; among them, 11 polyphenols and cis,trans-abscisic acid were quantified using UHPLC coupled with an LTQ-Orbitrap XL mass analyzer. For the first time chrysin, naringenin, pinocembrin, and galangin were quantified in some of the investigated berry species. The extraction efficiency of the two extraction systems, methanol and acetone, was investigated. It was found that acetone is a better extracting solvent for TPC, whereas more TAC was extracted by methanol. TPC in acetone extracts ranged from 177.51 to 459.71 mg gallic acid equiv/100 g frozen weight. TAC ranged from 5.39 to 96.94 mg cyanidin-3-glucoside/100 g frozen weight in methanol extracts. The amounts of both free and total ellagic acid were found to be higher in the acetone extract in comparison to the methanol extract.

Topics: Anthocyanins; Carbohydrates; Ellagic Acid; Flavanones; Flavonoids; Free Radical Scavengers; Fruit; Glucosides; Phenols; Plant Extracts; Polyphenols; Rosaceae; Serbia; Trace Elements

Several bacteria are able to degrade flavonoids either to use them as carbon sources or as a detoxification mechanism. Degradation pathways have been proposed for several bacteria, but the genes responsible are not known. We identified in the genome of the endophyte Herbaspirillum seropedicae SmR1 an operon potentially associated with the degradation of aromatic compounds. We show that this operon is involved in naringenin degradation and that its expression is induced by naringenin and chrysin, two closely related flavonoids. Mutation of fdeA, the first gene of the operon, and fdeR, its transcriptional activator, abolished the ability of H. seropedicae to degrade naringenin.

Topics: Bacterial Proteins; Biotransformation; Flavanones; Flavonoids; Gene Expression Regulation, Bacterial; Gene Knockout Techniques; Herbaspirillum; Operon

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 μg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 μg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 μg/ml. Flavone immobilized female adult worms at 31.2 μg/ml (MTT>80%) and microfilariae at 62.5 μg/ml. Rutin killed microfilariae at 125 μg/ml and inhibited MTT-reduction in female worms for >65% at 500 μg/ml. Naringin had adulticidal effects at 125 μg/ml while chrysin killed microfilariae at 250 μg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.

Topics: Animals; Brugia malayi; Coloring Agents; Disease Models, Animal; Elephantiasis, Filarial; Female; Filaricides; Flavanones; Flavonoids; Gerbillinae; Hesperidin; Humans; Male; Murinae; Rutin; Survival Analysis; Tetrazolium Salts; Thiazoles

Effect of two preparation (Croatian and Brazilian) of water-soluble derivative of propolis (WSDP), caffeic acid, quercetin, chrysin, naringenin (components present in WSDP) on the development of Ehrlich ascites tumour (EAT) was evaluated. Test components (50 mg/kg) were given perorally or intraperitoneally 2 h prior the intraperitonel injection of EAT (2 x 10(6)) cells. It was observed that all test compounds effectively inhibited tumour growth and the proliferation of EAT. The volume of ascitic fluid induced by EAT cells and total number of cells present in the peritoneal cavity was markedly reduced in EAT-bearing mice treated with test components. In treated mice the number of polymorphonuclear (PMN) cells in the peritoneal cavity was increased while the number of macrophages was decreased. The macrophage spreading activity revealed that WSDP and all test compounds affected the functional state of macrophages increasing their tumorcidal activity; the effect of WSDP was most pronounced indicating synergistic effect of components present in WSDP. Antitumor activity of WSDP may be the result of different specific mechanism(s) of flavonoids present as compared to individual flavonoid given alone. It is likely that the part of antitumor efficacy of test components against EAT cells was the results of increased activity of macrophages.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Ascitic Fluid; Caffeic Acids; Carcinoma, Ehrlich Tumor; Drug Synergism; Flavanones; Flavonoids; Injections, Intraperitoneal; Macrophages; Mice; Peritoneal Cavity; Phenols; Polyphenols; Propolis; Quercetin

Flavonoids and related structures (e.g., flavones, isoflavones, flavanones, catechins) exert various biological effects, including anticarcinogenic, antioxidant and (anti-)estrogenic effects, and modulation of sex hormone homeostasis. A key enzyme in the synthesis of estrogens from androgens is aromatase (cytochrome P450 19; CYP19). We investigated the effects of various natural and synthetic flavonoids on the catalytic activity and promoter-specific expression of aromatase in H295R human adrenocortical carcinoma cells. Natural flavones were consistently more potent inhibitors than flavanones. IC(50) values for 7-hydroxyflavone, chrysin, and apigenin were 4, 7, and 20 microM, respectively; for the flavanones 7-hydroxyflavanone and naringenin the IC(50) values were 65 and 85 microM, respectively. The steroidal aromatase inhibitor (positive control) 4-hydroxyandrostenedione had an IC(50) of 20 nM. The inhibition by apigenin and naringenin coincided with some degree of cytotoxicity at 100 microM. The natural flavonoid derivative rotenone (IC(50) 0.3 microM) was the most potent aromatase inhibitor tested. Several synthetic flavonoid and structurally related quinolin-4-one analogs inhibited aromatase activity. The most potent inhibitor was 4'-tert-butyl-quinolin-4-one (IC(50) 2 microM), followed by two 2-pyridinyl-substituted alpha-naphthoflavones (IC(50)s 5 and >30 microM). The two 2-pyridinyl-substituted gamma-naphthoflavones consistently produced biphasic concentration-response curves, causing about 1.5-fold aromatase induction at concentrations below 1 microM and inhibition above that level (IC(50)s 7 and >30 microM). The natural flavone quercetin and isoflavone genistein induced aromatase activity 4- and 2.5-fold induction, respectively, at 10 microM. This coincided with increased intracellular cAMP concentrations and increased levels of the cAMP-dependent pII and to a lesser extent 1.3 promoter-specific aromatase transcripts. These results shed light on the structure-activity relationships for aromatase inhibition as well as mechanisms of induction in human H295R cells.

Topics: Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Apigenin; Aromatase; Aromatase Inhibitors; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Induction; Flavanones; Flavonoids; Humans; Rotenone; Structure-Activity Relationship

Pig caecum was used under anaerobic conditions to metabolize flavonoids from several classes, i.e., chrysin 1, naringenin 2, quercetin 3, and hesperetin 4. Whereas chrysin 1 was not converted by the pig intestinal flora under the experimental conditions used, naringenin 2 was transformed to 3-(4-hydroxyphenyl)-propionic acid and 3-phenylpropionic acid. Quercetin 3 was metabolized to phloroglucinol, 3,4-dihydroxyphenylacetic acid, and 3,4-dihydroxytoluene. Hesperetin 4 was degraded via eriodictyol to 3-(3-hydroxyphenyl)-propionic acid and phloroglucinol. Structural elucidation of the formed metabolites was performed by high-performance liquid chromatography--diode array detection (HPLC-DAD) as well as HPLC-electrospray ionization--mass spectrometry (ESI-MS (MS)) and high resolution gas chromatography-mass spectrometry (HRGC-MS) analyses. The time course of microbial conversion of 2-4 was determined by HPLC-DAD analysis, revealing slow degradation of 2 and rapid transformation of 3 and 4. The results lead to the conclusion that the pig caecum model is a suitable ex vivo model for studying the intestinal degradation of flavonoids.

Topics: Animals; Cecum; Chromatography, High Pressure Liquid; Flavanones; Flavonoids; Gas Chromatography-Mass Spectrometry; Hesperidin; Models, Animal; Quercetin; Spectrometry, Mass, Electrospray Ionization; Swine

Thin-layer chromatography of ethanolic extract of propolis (EEP) from the continental and Adriatic regions of Croatia showed that 72.2% of propolis samples contain galangin, 88.8% of samples contain kaempferol, naringenin and apigenin and 66.6% of samples contain caffeic acid. Caffeic acid, pinocembrin, galangin, chrysin and naringenin were analyzed by HPLC. In all samples, pinocembrin was the dominant flavonoid. In samples from the Adriatic region, concentration of pinocembrin ranged from 0.03 to 6.14% (x = 2.87%) and in the continental region samples from 0 to 4.74% (x = 2.84%). Chrysin was found in all propolis samples in a concentration ranging from 0.22 to 5.32% (x = 1.86%) in the continental region samples and from 0.03 to 3.64% (x = 1.96%) in samples from the Adriatic region. Chrysin was followed by naringenin, ranging from 0 to 1.14% (x = 0.42%) in samples from the Adriatic region and from 0.22 to 2.41% (x = 0.60%) in the continental region samples. Concentration of caffeic acid ranged from 0 to 10.11% (x = 2.69%) in the Adriatic region samples and from 0.27 to 2.67% (x = 1.37%) in samples from the continental region of Croatia. Results of HPLC analyses suggest that propolis samples collected from various parts of Croatia do not differ markedly in contents of chrysin, pinocembrin, naringenin and galangin but differ in the concentration of caffeic acid. All EEPs significantly inhibited the growth of Bacillus subtilis in comparison with the control (80% ethanol) (p < 0.05), showing inhibition zones of 16 +/- 2 mm for samples from the continental region, and of 18 +/- 3 mm for samples from the Adriatic region. There was no significant difference in antimicrobial activity of EEPs from the continental and Adriatic regions of Croatia, suggesting that bactericidal activity depends on synergism of all phenolic compounds.

Topics: Animals; Anti-Infective Agents; Apigenin; Bacillus subtilis; Bees; Caffeic Acids; Croatia; Flavanones; Flavonoids; Kaempferols; Microbial Sensitivity Tests; Propolis

The effects of some flavonoids, a group of naturally occurring pigments one of which has been claimed to possess antidiabetic activities, on insulin release and 45Ca2+ handling have been studied in isolated rat islets of Langerhans. Insulin release was enhanced by approximately 44-70% when islets were exposed to either (-)epicatechin (0.8 mmol/l) or quercetin (0.01-0.1 mmol/l); others such as naringenin (0.1 mmol/l) and chrysin (0.08 mmol/l) inhibited hormone release by approximately 40-60%. These effects were observed only in the presence of 20 mmol glucose/l. Quercetin (0.01 mmol/l) and (-)epicatechin (0.8 mmol/l) both inhibited 45Ca2+ efflux in the presence and absence of extracellular Ca2+. In the presence of 20 mmol glucose/l both the short-term (5 min) and steady-state (30 min) uptake of 45Ca2+ were significantly increased by either quercetin or (-)epicatechin. These results suggest that the stimulatory compounds such as quercetin and (-)epicatechin may, at least in part, exert their effects on insulin release via changes in Ca2+ metabolism.

Topics: Animals; Calcium; Catechin; Flavanones; Flavones; Flavonoids; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Male; Quercetin; Rats; Rats, Inbred Strains