chrysin and hesperetin

The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE-II, is a type I integral membrane protein of 805 amino acids that contains 1 HEXXH-E zinc binding consensus sequence. ACE-II has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). In this study, the potential of some flavonoids presents in propolis to bind to ACE-II receptors was calculated with in silico. Binding constants of ten flavonoids, caffeic acid, caffeic acid phenethyl ester, chrysin, galangin, myricetin, rutin, hesperetin, pinocembrin, luteolin and quercetin were measured using the AutoDock 4.2 molecular docking program. And also, these binding constants were compared to reference ligand of MLN-4760. The results are shown that rutin has the best inhibition potentials among the studied molecules with high binding energy - 8.04 kcal/mol, and it is followed by myricetin, quercetin, caffeic acid phenethyl ester and hesperetin. However, the reference molecule has binding energy of - 7.24 kcal/mol. In conclusion, the high potential of flavonoids in ethanolic propolis extracts to bind to ACE-II receptors indicates that this natural bee product has high potential for COVID-19 treatment, but this needs to be supported by experimental studies.

Topics: Angiotensin-Converting Enzyme 2; Animals; Bees; Caffeic Acids; COVID-19 Drug Treatment; Flavanones; Flavonoids; Hesperidin; Humans; Luteolin; Molecular Docking Simulation; Phenylethyl Alcohol; Plant Extracts; Propolis; Quercetin; Rutin

Flavonoids are polyphenols frequently consumed in the diet they have been suggested to exert a number of beneficial actions on human health, including anti-inflammatory activity. This study investigated the immunomodulatory effects of two flavonoids, Chrysin and Hesperetin. The effects of flavonoids on B and T cell proliferation were assessed on splenocytes stimulated or not with mitogens. However, their effects on cytotoxic T lymphocyte (CTL) and natural killer (NK) activities were assessed in splenocytes co-incubated with target cells. We report for the first time that both tested flavonoids enhance lymphocyte proliferation at 3.12μM. Chrysin significantly inhibited lipopolysaccharide (LPS) and lectin stimulated splenocyte proliferation. Whereas, hesperetin enhanced LPS and lectin stimulated splenocyte proliferation. In addition, both flavonoids significantly enhance NK cell and CTL activities. Furthermore, our study demonstrated that depending on the concentrations, flavonoid molecules affect macrophage functions by modulating their lysosomal activity and nitric oxide (NO) release, suggesting a potential anti-inflammatory effect. We conclude that flavonoids such as chrysin and hesperetin may be potentially useful for modulating immune cell functions in physiological and pathological conditions and thus a good candidate as food addition component.

Topics: Animals; Cell Proliferation; Flavonoids; Hesperidin; Humans; Immunity, Cellular; Immunity, Humoral; Immunologic Factors; Intracellular Membranes; K562 Cells; Macrophages, Peritoneal; Male; Natural Killer T-Cells; Nitric Oxide; Permeability; Rats; Rats, Wistar; Spleen; T-Lymphocytes, Cytotoxic

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

The chemometrics approach was applied for the separation optimization of flavonoid markers (quercetin, hesperetin and chrysin) in honey using micellar liquid chromatography (MLC). The investigated method combines SPE of flavonoids from honey using C(18) cartridge and their separation and quantification by micellar liquid chromatography. A two level full factorial design was carried out to evaluate the effect of four experimental factors including concentration of SDS, alkyl chain length of the alcohol used as the organic modifier (N), volume percentage of the organic modifier (V(m)) and volume percentage of acetic acid (AcOH) in mobile phase on analytes retention times. Experiments for analytes retention times modeling and optimization of separation were performed according to central composite design. Multiple linear regression method was used for the construction of the best model based on experimental retention times. Pareto optimal method was used to find suitable compatibility between resolution and analysis time of analytes in honey. The optimum mobile phase composition for separation and determination of analytes in honey were [SDS]=0.124  mol/L; 7.8% v/v ethanol and 5.0% v/v AcOH. Limits of detection and linear range of flavonoid markers were 0.0079-0.0126, 0.05-50.0  mg/L, respectively.

Topics: Chromatography, Liquid; Flavonoids; Hesperidin; Honey; Micelles; Quercetin

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