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
Vine tea, a Chinese herbal medicine, is widely used in traditional Asian medicine to treat common health problems. Dihydromyricetin (DMY) is the main functional flavonoid compound extracted from vine tea. In recent years, preclinical studies have focused on the potential beneficial effects of dihydromyricetin, including glucose metabolism regulation, lipid metabolism regulation, neuroprotection, and anti-tumor effects. In addition, DMY may play a role in cardiovascular disease by resisting oxidative stress and participating in the regulation of inflammation. This review is the first review that summaries the applications of dihydromyricetin in cardiovascular diseases, including atherosclerosis, myocardial infarction, myocardial hypertrophy, and diabetic cardiomyopathy. We also clarified the underlying mechanisms and signaling pathways involved in the above process. The aim of this review is to provide a better understanding and quick overview for future researches of dihydromyricetin in the field of cardiovascular diseases, and more detailed and robust researches are needed for evaluation and reference.
- MeSH
- čaj MeSH
- flavonoly farmakologie terapeutické užití MeSH
- kardiovaskulární nemoci * farmakoterapie MeSH
- lidé MeSH
- oxidační stres MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism underlying the effects of DHM on alcohol metabolism is virtually unknown. The present paper is focused on clarifying the role of DHM in the liver alcohol elimination at its molecular level. First, impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and the enzyme induction in vivo was examined. Neither the ADH activity nor the enzyme expression were influenced by DHM. Next, the effect of DHM during alcohol intoxication were studied on primary hepatocytes isolated from EtOH-premedicated and untreated rats. The viability of cells exposed to alcohol, estimated based on the released enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was slightly affected by DHM. Although the expected hepatoprotective effect of DHM was not fully achieved, DHM (in a concentration manner) proved to reduce the level of ROS/RNS in hepatocytes. However, no change in the rate of alcohol metabolism in vivo was found when rats were administered with a single or repeated dose of ethanol supplemented with DHM. In conclusion, the proposed positive effect of DHM during alcohol intoxication has not been proven. Moreover, there is no effect of DHM on the alcohol metabolism. The "hoped-for" DHM hepatoprotective activity can be attributed to the reduction of ROS/RNS levels in cells.
- MeSH
- alkoholdehydrogenasa metabolismus MeSH
- antioxidancia farmakologie MeSH
- cytochrom P-450 CYP2E1 metabolismus MeSH
- ethanol metabolismus MeSH
- flavonoly farmakologie MeSH
- hepatocyty účinky léků metabolismus MeSH
- játra účinky léků metabolismus MeSH
- kultivované buňky MeSH
- metabolická inaktivace MeSH
- nitrosativní stres účinky léků MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy dusíku metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tvorba biofilmů a s ní související rostoucí rezistence mikroorganismů ukazuje na potřebu hledání nových přírodních látek, které při současném podání s antibiotikem zvýší jejich biologickou aktivitu. Zároveň je nutné zajistit netoxicitu těchto látek. Jednou z možných alternativ je použití sekundárních metabolitů rostlin, například polyfenolů. Tyto metabolity se přirozeně vyskytují v ovoci, zelenině, obilovinách, ořeších, ale také v rostlinných produktech jako je víno, pivo, čaj a kakao. V současné době se přesunula pozornost k rostlinným polyfenolům pocházejícím z extraktu vinné révy. Vinná réva obsahuje velké množství polyfenolových látek, např. resveratrolu či polydatinu. Odpadní vinařské produkty jsou bohaté na polyfenolové látky, které by mohly přispět k řešení problému při rezistenci mikroorganismů k běžně používaným antibiotikům, zároveň by se tím vyřešil problém s nakládáním s vinařskými odpady.
The formation of biofilms and the associated increasing resistance of microorganisms shows the need to search for novel natural substances that would increase the biological activity of antibiotics if used together. It is also necessary to ensure the non‑‑toxicity of these substanes. One of the possibilities could be the application of plant secondary metabolites. These metabolites naturally occur in fruits, vegetables, cereals, nuts but also in plant products such as wine, beer, tea and cocoa. At present, attention has been paid to plant polyphenols from the grapevine extracts. Grapevine contains a lot of polyphenols, such as resveratrol or polydatin. Waste wine products are also rich in polyphenol substances that could help solve the problem of antibiotic resistance as well as the management of wine waste.
- MeSH
- antiinfekční látky izolace a purifikace MeSH
- antioxidancia MeSH
- biofilmy účinky léků MeSH
- farmakologické účinky - molekulární mechanismy MeSH
- flavonoidy farmakologie izolace a purifikace MeSH
- flavonoly farmakologie izolace a purifikace MeSH
- glukosidy farmakologie izolace a purifikace MeSH
- katechin farmakologie izolace a purifikace MeSH
- kempferoly farmakologie izolace a purifikace MeSH
- kyselina mléčná analogy a deriváty farmakologie izolace a purifikace MeSH
- quercetin farmakologie izolace a purifikace MeSH
- resveratrol farmakologie izolace a purifikace MeSH
- stilbeny farmakologie izolace a purifikace MeSH
- Vitis * chemie MeSH
- Publikační typ
- práce podpořená grantem MeSH
OBJECTIVES: Dihydromyricetin (DHM) is a flavonoid, which has been shown to antagonize effects of ethanol intoxication. As a potential pharmacological agent, its biological interactions with enzymes metabolizing foreign compounds should be tested. Thus, the aim of this study was to analyze the influence of DHM on the induction and metabolic activity of selected cytochromes P450 (CYPs). METHODS: After flavonoid administration by oral gavage to stomach the CYP expression at protein and mRNA levels was determined in rat liver and small intestine. The effects of flavonoids on CYP1A1/2, CYP1A2 or CYP2B1/2 enzyme activities in microsomes were measured using marker activities of these enzymes. Flavonoid-mediated inhibition of recombinant CYP1A2 was also assayed with luciferin-ME substrate. The flavonoid interaction with aryl hydrocarbon receptor (AhR) was assayed by reporter luciferase activity in Hep2G cells. RESULTS: The value of half maximal inhibitory concentration of DHM for CYP1A1/2, CYP1A2, and CYP2B1 were determined to be 4.1, 14.2, and 98.5 mmol.L(-1), respectively. With the exception of a weak induction of CYP2B1 and CYP1A2 in the middle part of small intestine and in the liver, respectively, DHM did not affect the CYP expression at protein levels. On the contrary, real-time PCR revealed elevated expression of CYP1A1 and CYP1A2 mRNA in proximal part of the small intestine while decreased in the middle part. In the study utilizing the HepG2 cells, DHM showed only an additive effect on the benzo[a]pyrene-mediated activation of Ah receptor. CONCLUSIONS: Dihydromyricetin doesn't significantly interfere with metabolic activity of CYP1A1/2 and CYP2B1 enzymes.
- MeSH
- flavonoly farmakologie MeSH
- inhibiční koncentrace 50 MeSH
- játra účinky léků enzymologie MeSH
- karcinogeny metabolismus MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- messenger RNA účinky léků metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 účinky léků genetika metabolismus MeSH
- tenké střevo účinky léků enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Plod borůvky černé patří mezi nejzdravější potraviny, které pomáhají v prevenci a někdy i při léčbě určitých onemocnění. Všechny rostlinné části borůvky černé jsou potenciálními zdroji významných fenolických látek s rozmanitými biologickými účinky.
The bilberry fruit is among the healthiest foods that aid in preventing and, sometimes, even treating certain conditions. All the plant components of the bilberry are potential sources of important phenolic substances with diverse biological effects.
- MeSH
- anthokyaniny farmakologie MeSH
- cinnamáty farmakologie MeSH
- financování organizované MeSH
- flavonoly farmakologie MeSH
- fytoterapie MeSH
- lidé MeSH
- Vaccinium myrtillus chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- herbáře MeSH
- Klíčová slova
- Morine, Methocel,
- MeSH
- antioxidancia farmakologie MeSH
- chelátory farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- flavonoly farmakologie MeSH
- ischemie enzymologie farmakoterapie MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus patologie účinky léků MeSH
- methylcelulosa farmakologie MeSH
- modely u zvířat MeSH
- reperfuze MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
