Myricetin (MYR) and dihydromyricetin (DHM) are classified as natural flavonoids. Both substances are known for their anti-inflammatory and antioxidant properties. In this study, an in vitro model of inflammation was demonstrated on monolayers of scratched fibroblasts or keratinocytes exposed to LPS from Pseudomonas aeruginosa for six hours. MYR and DHM were subsequently applied to the cells for 24 hours at sub toxic concentrations (5-15 μM). Inflammatory parameters were analysed in collected cell medium and lysate after the incubation period using the Enzyme-Linked ImmuneSorbent Assay (ELISA) and Western blot. Both flavonoids inhibit the production of pro-inflammatory cytokines (IL-6, IL-8) in LPS-stimulated skin cells as well as the decreased level of MMP-1 in fibroblasts. However, the application of MYR and DHM dose dependently increased the level of MMP-1 in keratinocytes. In our experiments, we focused on the anti-glycation activity of MYR and DHM, where the higher concentration of MYR seems to be more effective.

• Klíčová slova
• Myricetin, Dihydromyricetin,
• MeSH
• flavonoidy terapeutické užití   MeSH
• hodnocení léčiv MeSH
• hojení ran * účinky léků   MeSH
• lidé MeSH
• rány a poranění MeSH
• zánět MeSH
• Check Tag
• lidé MeSH

Authentic standards of food flavonoids are important for human metabolic studies. Their isolation from biological materials is impracticable; however, they can be prepared in vitro. Twelve sulfated metabolites of luteolin, myricetin, and ampelopsin were obtained with arylsulfotransferase from Desulfitobacterium hafniense and fully characterized by high-performance liquid chromatography, MS, and NMR. The compounds were tested for their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and N,N-dimethyl-p-phenylenediamine radicals, to reduce ferric ions and Folin-Ciocalteu reagent, and to inhibit tert-butyl hydroperoxide-induced lipid peroxidation of rat liver microsomes. The activity differed considerably even between monosulfate isomers. The parent compounds and myricetin-3'-O-sulfate were the most active while other compounds displayed significantly lower activity, particularly luteolin sulfates. No mutagenic activity of the parent compounds and their main metabolites was observed; only myricetin showed minor pro-mutagenicity. The prepared sulfated metabolites are now available as authentic standards for future in vitro and in vivo metabolic studies.

• MeSH
• antioxidancia chemie   farmakologie   MeSH
• arylsulfotransferasa chemie   MeSH
• bakteriální proteiny chemie   MeSH
• biofyzikální jevy MeSH
• biokatalýza MeSH
• Desulfitobacterium enzymologie   MeSH
• flavonoidy chemie   metabolismus   farmakologie   MeSH
• isomerie MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• luteolin chemie   metabolismus   farmakologie   MeSH
• molekulární struktura MeSH
• peroxidace lipidů účinky léků   MeSH
• sírany chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNA-expressed CYP2E1 with the Ki=52.1±6.31μM. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki=15.4±1.52μM, and myricetin - noncompetitively with the Ki=74.6±7.99μM. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender-dependent.

• MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• hydroxylace MeSH
• inhibitory cytochromu P450 CYP2E1 farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• kumariny metabolismus   MeSH
• lidé MeSH
• nitrofenoly metabolismus   MeSH
• quercetin analogy a deriváty   farmakologie   MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin-3'-O-sulfate (M3'S), AMP, and ampelopsin-4'-O-sulfate (A4'S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion-transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3'S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3'S, AMP, and A4'S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3'S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3'S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR-containing dietary supplements may affect the OATP-mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3'S.

• MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• cytochrom P450 CYP2C9 metabolismus   MeSH
• flavonoidy * farmakologie   MeSH
• flavonoly farmakologie   MeSH
• lidé MeSH
• polypeptid C přenášející organické anionty * metabolismus   MeSH
• přenašeče organických aniontů * metabolismus   MeSH
• sérový albumin metabolismus   MeSH
• sírany metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

We investigated gender-related differences in the ability of selected flavonoids and phenolic compounds to modify porcine hepatic CYP450-dependent activity. Using pools of microsomes from male and female pigs, the inhibition of the CYP families 1A, 2A, 2E1, and 3A was determined. The specific CYP activities were measured in the presence of the following selected compounds: rutin, myricetin, quercetin, isorhamnetin, p-coumaric acid, gallic acid, and caffeic acid. We determined that myricetin and isorhamnetin competitively inhibited porcine CYP1A activity in the microsomes from both male and female pigs but did not affect the CYP2A and CYP2E1. Additionally, isorhamnetin competitively inhibited CYP3A in both genders. Noncompetitive inhibition of CYP3A activity by myricetin was observed only in the microsomes from male pigs, whereas CYP3A in female pigs was not affected. Quercetin competitively inhibited CYP2E1 and CYP1A activity in the microsomes from male pigs and irreversibly CY3A in female pigs. No effect of quercetin on CYP2E1 was observed in the microsomes from female pigs. Neither phenolic acids nor rutin affected CYP450 activities. Taken together, our results suggest that the flavonoids myricetin, isorhamnetin, and quercetin may affect the activities of porcine CYP1A, CYP3A, and CYP2E1 in a gender-dependent manner.

• MeSH
• inhibitory cytochromu P450 farmakologie   MeSH
• jaterní mikrozomy enzymologie   MeSH
• pohlavní dimorfismus * MeSH
• prasata MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Objectives: The scope of the present study was to specify the therapeutic potential for neurodegenerative diseases through evaluating cholinesterase and tyrosinase (TYR) inhibitory and antioxidant activity of Lysimachia verticillaris (LV), and to isolate the major compounds considering the most active fraction. Materials and Methods: The methanol extract (ME) of LV and the chloroform, ethyl acetate (EtOAC), and aqueous fractions obtained from it were used for biological activity and isolation studies. The ME and all fractions were tested for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and TYR inhibitory and antioxidant potentials using ELISA microtiter assays. Seven major compounds were isolated from the active EtOAC fraction by semi-preparative high performance liquid chromatography. The structures of the compounds were elucidated by several spectroscopic methods. Results: Marked AChE inhibitory activity was observed in the EtOAC fraction (6337±1.74%), BChE inhibitory activity in the ME and EtOAC fraction (85.84±3.01% and 83.82±3.93%), total phenol content in the EtOAC fraction (261.59±3.95 mg equivalent of gallic acid/1 g of extract) and total flavonoid contents in the EtOAC fraction (515.54±2.80 mg equivalent of quercetin/1 g of extract), and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and ferric-reducing antioxidant power values in the aqueous and EtOAC fractions (92.54±0.67%, 92.11±0.30%; 2.318±0.054, 2.224±0.091, respectively). Accordingly, the isolation studies were carried out on the EtOAC fractions. Compounds 1-7 (gallic acid, (+)-catechin, myricetin 3-O-arabinofuranoside, myricetin 3-O-α-rhamnopyranoside, quercetin 3-O-β-glucopyranoside, quercetin 3-O-arabinofuranoside, and quercetin 3-O-α-rhamnopyranoside, respectively) were isolated from the active EtOAC fraction. Conclusion: LV may be a potential herbal source for treatment of neurodegenerative diseases based on its strong antioxidant activity and significant cholinesterase inhibition similar to that of the reference.

• Publikační typ
• časopisecké články MeSH

Nowadays, much research attention is focused on underutilized berry crops due to the high antioxidant activity of fruits. Black crowberry (Empetrum nigrum L.) represents an important source of flavonols (quercetin, rutin, myricetin, naringenin, naringin, morin, and kaempferol) and anthocyanins. The fruit components could be utilised as natural colourants or as a part of functional foods and, because of the high antioxidant activity, the berries of black crowberry can be used in the treatment of diseases accompanied with inflammation, or as an effective antibacterial and antifungal remedy. Moreover, the reduction of lipid accumulation and total cholesterol as well as an improvement of postprandial hyperglycaemia have been proven. This review summarizes for the first time the main antioxidants (flavonoids) of black crowberry fruits, with a focus on their health promoting activity.

• MeSH
• Ericaceae chemie   MeSH
• flavonoidy farmakologie   MeSH
• lidé MeSH
• ovoce chemie   MeSH
• podpora zdraví MeSH
• rostlinné extrakty farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The antiurease activity of the aqueous extracts of 42 plants growing in the Czech Republic was investigated. A phenol-hypochlorite reaction was used for the determination of ammonia produced by urease. The inhibitory activity of the extracts at a concentration of 0.2 mg/mL varied from 17.8% to 80.0%. Extracts from six Potentilla species expressed inhibitory activity against jack bean urease. They were further investigated for their phenolic constituents and the major compounds were subjected to molecular docking. The results revealed that both jack bean urease and Helicobacter pylori urease were inhibited by quercetin-3-O-β-D-galactopyranoside-6″-gallate (1), myricetin-3-O-β-D-glucuronide (2), tiliroside (3) and B-type procyanidin (4). The antiurease activity of the investigated Potentilla species is probably due to the presence of complex phenolic constituents such as flavonoid glycosides and catechin dimers.

• MeSH
• algoritmy MeSH
• Canavalia enzymologie   MeSH
• fenoly chemie   izolace a purifikace   farmakologie   MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• galaktosidy chemie   izolace a purifikace   farmakologie   MeSH
• Helicobacter pylori účinky léků   MeSH
• infekce vyvolané Helicobacter pylori farmakoterapie   MeSH
• léčivé rostliny chemie   MeSH
• Potentilla chemie   MeSH
• quercetin analogy a deriváty   MeSH
• ureasa antagonisté a inhibitory   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Neurological illnesses are multifactorial incurable debilitating disorders that may cause neurodegeneration. These diseases influence approximately 30 million people around the world. Despite several therapies, effective management of such disorders remains a global challenge. Thus, natural products might offer an alternative therapy for the treatment of various neurological disorders. Polyphenols, such as curcumin, resveratrol, myricetin, mangiferin and naringin (NRG) have been shown to possess promising potential in the treatment of neurogenerative illness. In this review, we have targeted the therapeutic potential of naringin as a neuroprotective agent. The overall neuroprotective effects and different possible underlying mechanisms related to NRG are discussed. In light of the strong evidence for the neuropharmacological efficacy of NRG in various experimental paradigms, it is concluded that this molecule should be further considered and studied as a potential candidate for neurotherapeutics, focusing on mechanistic and clinical trials to ascertain its efficacy.

• MeSH
• flavanony chemie   terapeutické užití   MeSH
• lidé MeSH
• nemoci nervového systému farmakoterapie   MeSH
• neuroprotektivní látky chemie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH