Onosma riedliana Binzet & Orcan, a traditionally used plant species, has been explored for its therapeutic potential in this study. The work presented here is the first report on the phenolic profile and biological activity of this species. Three extracts of varying polarity were prepared, with the methanolic extract containing the highest phenolic content (97.62 ± 0.20 mgGAE/g). Key phenolic compounds identified included pinoresinol, hesperidin, 4-hydroxybenzoic acid, and p-coumaric acid. The methanolic extract exhibited exceptional antioxidant properties, rivaling Trolox as a positive control, primarily attributed to hesperidin and luteolin. Moreover, the ethyl acetate extract demonstrated remarkable inhibition of cholinesterase and tyrosinase enzymes, while the methanolic extract displayed potent activity against carbohydrate hydrolytic enzymes, α-amylase and α-glucosidase. Again, phenolic compounds were shown to be responsible for the inhibition of cholinesterases and tyrosinase, but not for α-amylase and α-glucosidase. These findings underscore Onosma riedliana's potential for incorporation into diverse pharmaceutical formulations, given its multifaceted bioactivity.
Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to "pulling the rug out from under", effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.
- MeSH
- biomechanika MeSH
- buněčné mikroprostředí účinky léků MeSH
- flavanony farmakologie chemie MeSH
- jaterní cirhóza * farmakoterapie metabolismus patologie MeSH
- jaterní hvězdicovité buňky * metabolismus cytologie účinky léků MeSH
- kolagen typu I metabolismus MeSH
- kyselina askorbová * farmakologie metabolismus chemie MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.
- MeSH
- antiflogistika farmakologie chemie MeSH
- autofagie účinky léků MeSH
- flavanony * farmakologie chemie MeSH
- komplexní sloučeniny * farmakologie chemická syntéza chemie MeSH
- lidé MeSH
- měď * chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Detralex,
- MeSH
- bércové vředy * farmakoterapie komplikace terapie MeSH
- diosmin terapeutické užití MeSH
- dospělí MeSH
- hesperidin terapeutické užití MeSH
- kardiovaskulární látky terapeutické užití MeSH
- lidé MeSH
- náhrada léků MeSH
- posttrombotický syndrom chirurgie farmakoterapie MeSH
- žilní insuficience komplikace terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model. METHODS: From each drug, five tablets were weighed. A homogenate was prepared, and 25 mg of crushed homogenized tablets were weighed into 25 ml volumetric flasks. Dissolved in MeOH and added two drops of saturated NaOH solution. The samples were filtered into vials (Teflon, 0.45 μm) and used for analysis. An Ultimate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA, USA) consisting of a quaternization pump, autosampler, column thermostat and DAD (UV/VIS detector) was used. The composition of the mobile phase proceeded in a linear gradient from 30% methanol and 70% phosphoric acid (0.15%) in water at time t=0 min. to 80% methanol and 20% phosphoric acid (0.15%) at time t=15 min., at a constant mobile phase flow rate of 1.2 mL/min. Detection was performed using a DAD detector in the 190-450 nm wavelength range. The content of monitored flavonoids was calculated from peaks at a wavelength of 277 nm, in which both flavonoids have their absorption maxima. The static digestive model was used to simulate the digestive phase from the oral cavity to the corresponding intestinal phase. RESULTS: The content of diosmin and hesperidin (mg per table) for a prescription drug: Detralex: 480 mg, 26 mg. The content of diosmin and hesperidin (mg per tablet) for OTC drugs: Venostop: 502 mg, 48 mg, Diosminol: 520 mg, 50 mg, Devenal: 496 mg, 49 mg, Diohes: 493 mg, 46 mg. Digestion did not affect the solubility of all tested drugs. The active substances could not be determined in the non-alkalized sample. After alkalization, part of the insoluble matter was visibly dissolved and converted to a yellow flavonoid complex. Neither diosmin nor hesperidin could be identified afterwards. CONCLUSIONS: Our experimental results show that the contents of both listed active substances, diosmin and hesperidin, met the declared amounts in all tested medicaments. Digestion simulation showed identical behaviour in prescription and OTC venotonics. The active substances could not be determined in the non-alkalized sample. Digestion did not affect the solubility of the tested drugs.
- Klíčová slova
- mikronizovaná purifikovaná flavonoidní frakce,
- MeSH
- diosmin farmakologie terapeutické užití MeSH
- flavonoidy * terapeutické užití MeSH
- hesperidin farmakologie terapeutické užití MeSH
- kardiovaskulární látky farmakologie terapeutické užití MeSH
- lidé MeSH
- prospektivní studie MeSH
- žilní insuficience * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- mikronizovaná purifikovaná flavonoidní frakce,
- MeSH
- bércové vředy etiologie terapie MeSH
- diosmin aplikace a dávkování farmakologie terapeutické užití MeSH
- flavonoidy farmakologie terapeutické užití MeSH
- hesperidin aplikace a dávkování farmakologie terapeutické užití MeSH
- hojení ran MeSH
- kardiovaskulární látky aplikace a dávkování farmakologie toxicita MeSH
- lidé MeSH
- žilní insuficience * komplikace patofyziologie terapie MeSH
- Check Tag
- lidé MeSH
Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.
- MeSH
- hesperidin * farmakologie MeSH
- hyaluronoglukosaminidasa MeSH
- kolagenasy metabolismus MeSH
- lidé MeSH
- pankreatická elastasa MeSH
- rhamnosa * farmakologie MeSH
- stárnutí kůže * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Metabolický syndrom je rozšířen zejména v ekonomicky vyspělých částech světa. Celosvětově je jím postiženo 20–25 % dospělé populace, ale v současnosti je pozorován častěji i u dětí a dospívajících. Standardní léčba často zahrnuje polyfarmakoterapii, která zvyšuje riziko vedlejších účinků způsobených mezilékovými (drug-drug) interakcemi. Proto je vhodné hledat alternativní zdroje pro podporu léčby komponent metabolického syndromu. Přírodní polyfenolické sloučeniny, zpravidla obsažené v tzv. funkčních potravinách, jsou vzhledem k jejich biologické aktivitě a příznivému vlivu na lidský organismus pro tuto problematiku vhodným kandidátem. Mezi aktuálně studované a užívané přírodní polyfenolické sloučeniny s pozitivním vlivem na složky metabolického syndromu patří quercetin, troxerutin, diosmin, hesperidin nebo silybin. Tyto polyfenoly, kromě antioxidačních a protizánětlivých účinků mají i další pozitivní vlastnosti, které velmi často násobně převyšují jejich vedlejší nežádoucí účinky během jejich užití ve farmakoterapii.
Metabolic syndrome is diagnosed mainly in people of economically developed parts of the world and it affects 20–25% of the adult population worldwide. Nowadays, it is also more frequently diagnosed in children and adolescents. In addition to standard treatment that often involves polypharmacotherapy, and thus increases risk of side effects caused by drugdrug interactions, it is appropriate to look for alternative tools to support the treatment of metabolic syndrome components. Natural polyphenolic compounds, usually present in the so-called functional foods, are suitable candidates for that matter, due to the bioactivity and beneficial effects on the human body. Quercetin, troxerutin, diosmin, hesperidin or silybin are among the currently studied and used natural polyphenolic compounds with a positive effect on aspects of the metabolic syndrome. In addition to their antioxidant and anti-inflammatory effects, these compounds have other positive properties that very often outweigh their side effects whilst their usage in the pharmacotherapy.
- Klíčová slova
- troxerutin,
- MeSH
- diosmin farmakologie terapeutické užití MeSH
- hesperidin farmakologie terapeutické užití MeSH
- lidé MeSH
- metabolický syndrom * farmakoterapie patologie MeSH
- potravní doplňky * MeSH
- quercetin farmakologie terapeutické užití MeSH
- silibinin farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Klíčová slova
- Cyclo 3 Fort,
- MeSH
- diabetes mellitus 2. typu komplikace patofyziologie MeSH
- hesperidin terapeutické užití MeSH
- kyselina askorbová terapeutické užití MeSH
- lidé MeSH
- rostlinné extrakty terapeutické užití MeSH
- Ruscus MeSH
- sekundární prevence MeSH
- žilní insuficience * diagnostické zobrazování farmakoterapie komplikace MeSH
- Check Tag
- lidé MeSH
