Bacteria represent an underexplored source of diglycosidases. Twenty-five bacterial strains from the genera Actinoplanes, Bacillus, Corynebacterium, Microbacterium, and Streptomyces were selected for their ability to grow in diglycosylated flavonoids-based media. The strains Actinoplanes missouriensis and Actinoplanes liguriae exhibited hesperidin deglycosylation activity (6-O-α-L-rhamnosyl-β-D-glucosidase activity, EC 3.2.1.168), which was 3 to 4 orders of magnitude higher than the corresponding monoglycosidase activities. The diglycosidase production was confirmed in A. missouriensis by zymographic assays and NMR analysis of the released disaccharide, rutinose. The gene encoding the 6-O-α-L-rhamnosyl-β-D-glucosidase was identified in the genome sequence of A. missouriensis 431(T) (GenBank accession number BAL86042.1) and functionally expressed in Escherichia coli. The recombinant protein hydrolyzed hesperidin and hesperidin methylchalcone, but not rutin, which indicates its specificity for 7-O-rutinosylated flavonoids. The protein was classified into the glycoside hydrolase family 55 (GH55) in contrast to the known eukaryotic diglycosidases, which belong to GH1 and GH5. These findings demonstrate that organisms other than plants and filamentous fungi can contribute to an expansion of the diglycosidase toolbox.
- MeSH
- Bacterial Proteins genetics metabolism MeSH
- beta-Glucosidase genetics metabolism MeSH
- Chalcones chemistry metabolism MeSH
- Disaccharides chemistry metabolism MeSH
- Escherichia coli genetics metabolism MeSH
- Gene Expression MeSH
- Flavonoids chemistry metabolism MeSH
- Phylogeny MeSH
- Glycosides chemistry metabolism MeSH
- Hesperidin analogs & derivatives chemistry metabolism MeSH
- Hydrolysis MeSH
- Cloning, Molecular MeSH
- Micromonosporaceae classification genetics metabolism MeSH
- Recombinant Proteins genetics metabolism MeSH
- Rhamnose chemistry metabolism MeSH
- Substrate Specificity MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Mikronizovaná purifikovaná flavonoidní frakce (diosmin, hesperidin) zlepšuje žilní tonus a lymfatickou drenáž a snižuje kapilární hyperpermeabilitu, protože chrání mikrocirkulaci před zánětlivými procesy. Ve dvou randomizovaných dvojitě slepých studiích trvajících dva měsíce se léčbou diosminem s hesperidinem v dávce 500 mg dvakrát denně významně zmenšil obvod kotníku nebo lýtka, došlo ke zmírnění příznaků chronické žilní insuficience i ke zlepšení pletysmografických ukazatelů ve srovnání s placebem. V nezaslepeném i dvojitě slepém uspořádání bylo prokázáno úplné zhojení významně většího počtu chronických bércových vředů do průměru 10 cm včetně při léčbě diosminem s hesperidinem v dávce 500 mg dvakrát denně v kombinaci se standardní terapií (kompresivní a lokální léčba) v trvání 2 až 6 měsíců ve srovnání se standardní terapií samotnou nebo s placebem. Bylo dosaženo významného zmenšení trvání a/nebo intenzity příznaků vnitřních hemoroidů 1. nebo 2. stupně při podávání diosminu s hesperidinem v dávce 1 500 mg denně po 4 dny a v dávce 1 000 mg dvakrát denně po další 3 dny.
Micronized purified flavonoid fraction (diosmin, hesperidin) increases venous tone, improves lymphatic drainage and reduces capillary hyperpermeability by protecting the microcirculation from damaging inflammatory processes. Two two-month double-blind trials proved diosmin with hesperidin at a dose of 500 mg twice daily to be effective in significantly reducing ankle or calf circumference, improving symptoms of chronic venous insufficiency and plethysmography parameters compared to placebo. Both nonblinded and double blind trials sho wed complete healing of a significantly higher number of chronic leg ulcers less than or equal to 10 cm in diameter for a combination of 450 mg of diosmin and 50 mg of hesperidin twice daily plus standard therapy (compressive and local therapy) for 2 to 6 months compared to both standard therapy alone and placebo. Length and/or intensity of symptoms of stage 1 and 2 internal hemorrhoids was significantly reduced in patients given 1 500 mg of diosmin plus hesperidin twice daily for four days followed by 1 000 mg twice daily for three more days.
- Keywords
- Detralex,
- MeSH
- Varicose Ulcer drug therapy MeSH
- Diosmin pharmacology chemistry therapeutic use MeSH
- Pharmacokinetics MeSH
- Flavonoids pharmacology therapeutic use MeSH
- Hesperidin pharmacology chemistry therapeutic use MeSH
- Humans MeSH
- Lymphatic Vessels drug effects MeSH
- Venous Insufficiency drug therapy MeSH
- Check Tag
- Humans MeSH
