Aluminum accumulation, glutathione (GSH) and malondialdehyde (MDA) concentrations as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in erythrocytes and brain and liver homogenates of BALB/c mice treated with Al3+ (7.5 mg/kg/day (0.15 LD50) as AlCl3 (37.08 mg/kg/day), whereas HCl (30.41 mg/kg/day) was used as Cl- control, the treatments were performed for 21 days, i.p., in the presence and absence of rosmarinic acid (0.2805 mg/kg/day (0.05 LD50), 21 days, i.g.) or carvacrol (0.0405 mg/kg/day (0.05 LD50), 21 days, i.g.). The treatment with AlCl3 increased GSH concentration in erythrocytes only slightly and had no effect on brain and liver homogenates. Rosmarinic acid and carvacrol strongly increased GSH concentration in erythrocytes but decreased it in brain and liver homogenates. However, AlCl3 treatment led to Al accumulation in mice blood, brain, and liver and induced oxidative stress, assessed based on MDA concentration in the brain and liver. Both rosmarinic acid and carvacrol were able to counteract the negative Al effect by decreasing its accumulation and protecting tissues from lipid peroxidation. AlCl3 treatment increased CAT activity in mice brain and liver homogenates, whereas the administration of either rosmarinic acid or carvacrol alone or in combination with AlCl3 had no significant effect on CAT activity. SOD activity remained unchanged after all the treatments in our study. We propose that natural herbal phenolic compounds rosmarinic acid and carvacrol could be used to protect brain and liver against aluminum induced oxidative stress leading to lipid peroxidation.

• Klíčová slova
• aluminum toxicity, brain, carvacrol, lipid peroxidation, liver, oxidative stress, rosmarinic acid,
• MeSH
• antioxidancia farmakologie   MeSH
• biologické přípravky chemie   farmakologie   MeSH
• cinnamáty chemie   farmakologie   MeSH
• cymeny chemie   farmakologie   MeSH
• depsidy chemie   farmakologie   MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• hliník škodlivé účinky   chemie   MeSH
• játra účinky léků   metabolismus   MeSH
• kyselina rozmarýnová MeSH
• malondialdehyd metabolismus   MeSH
• mozek účinky léků   metabolismus   MeSH
• myši MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• biologické přípravky MeSH
• carvacrol MeSH Prohlížeč
• cinnamáty MeSH
• cymeny MeSH
• depsidy MeSH
• hliník MeSH
• malondialdehyd MeSH

The aim of our study was to increase the extraction efficiency of carvacrol, rosmarinic, oleanolic and ursolic acid from the different species of oregano herbs (Origanum onites L., Origanum vulgare spp. hirtum and Origanum vulgare L.). Various extraction methods (ultrasound-assisted, heat-reflux, continuous stirring, maceration, percolation) and extraction conditions (different solvent, material:solvent ratio, extraction temperature, extraction time) were used, and the active substances were determined by HPLC. The lowest content of carvacrol, rosmarinic, oleanolic and ursolic acid was obtained by percolation. During heat-reflux extraction, the content of active substances depended on the solvent used: ethanol/non-aqueous solvent (glycerol or propylene glycol) mixture was more effective compared with ethanol alone. The results showed that for each species of oregano the most optimal extraction method should be selected to maximize the content of biologically active substances in the extracts.

• Klíčová slova
• HPLC, Origanum, carvacrol, extraction, oleanolic acid, rosmarinic acid, ursolic acid,
• MeSH
• cinnamáty izolace a purifikace   MeSH
• cymeny MeSH
• depsidy izolace a purifikace   MeSH
• dobromysl (rod) chemie   klasifikace   MeSH
• kyselina olenalová izolace a purifikace   MeSH
• kyselina rozmarýnová MeSH
• kyselina ursolová MeSH
• molekulární struktura MeSH
• monoterpeny izolace a purifikace   MeSH
• rostlinné extrakty chemie   MeSH
• rozpouštědla MeSH
• triterpeny izolace a purifikace   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• carvacrol MeSH Prohlížeč
• cinnamáty MeSH
• cymeny MeSH
• depsidy MeSH
• kyselina olenalová MeSH
• monoterpeny MeSH
• rostlinné extrakty MeSH
• rozpouštědla MeSH
• triterpeny MeSH

SCOPE: Aberrant vascular smooth muscle cell (VSMC) proliferation is involved in atherosclerotic plaque formation and restenosis. Mediterranean spices have been reported to confer cardioprotection, but their direct influence on VSMCs has largely not been investigated. This study aims at examining rosmarinic acid (RA) and 11 related constituents for inhibition of VSMC proliferation in vitro, and at characterizing the most promising compound for their mode of action and influence on neointima formation in vivo. METHODS AND RESULTS: RA, rosmarinic acid methyl ester (RAME), and caffeic acid methyl ester inhibit VSMC proliferation in a resazurin conversion assay with IC50 s of 5.79, 3.12, and 6.78 µm, respectively. RAME significantly reduced neointima formation in vivo in a mouse femoral artery cuff model. Accordingly, RAME leads to an accumulation of VSMCs in the G0 /G1 cell-cycle phase, as indicated by blunted retinoblastoma protein phosphorylation upon mitogen stimulation and inhibition of cyclin-dependent kinase 2 in vitro. CONCLUSION: RAME represses PDGF-induced VSMC proliferation in vitro and reduces neointima formation in vivo. These results recommend RAME as an interesting compound with VSMC-inhibiting potential. Future metabolism and pharmacokinetics studies might help to further evaluate the potential relevance of RAME and other spice-derived polyphenolics for vasoprotection.

• Klíčová slova
• Mediterranean spices, neointima formation, rosmarinic acid, rosmarinic acid methyl ester, vascular smooth muscle cells,
• MeSH
• cévní endotel cytologie   účinky léků   patologie   MeSH
• cinnamáty aplikace a dávkování   škodlivé účinky   farmakologie   terapeutické užití   MeSH
• depsidy aplikace a dávkování   škodlivé účinky   farmakologie   terapeutické užití   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   MeSH
• fosforylace účinky léků   MeSH
• kardiovaskulární látky škodlivé účinky   farmakologie   terapeutické užití   MeSH
• koření analýza   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kyselina rozmarýnová MeSH
• lidé MeSH
• metylace MeSH
• myši inbrední C57BL MeSH
• náhodné rozdělení MeSH
• patologická angiogeneze metabolismus   patologie   prevence a kontrola   MeSH
• posttranslační úpravy proteinů účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• retinoblastomový protein metabolismus   MeSH
• rozmarýn chemie   růst a vývoj   MeSH
• strava středomořská MeSH
• svaly hladké cévní cytologie   účinky léků   metabolismus   patologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Středomoří MeSH
• Názvy látek
• cinnamáty MeSH
• depsidy MeSH
• kardiovaskulární látky MeSH
• retinoblastomový protein MeSH
• rosmarinic acid methyl ester MeSH Prohlížeč

UVA radiation provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in the exposed cells leading to extensive cellular damage and cell death either by apoptosis or necrosis. One approach to protecting human skin against the harmful effects of UV radiation is by using herbal compounds as photoprotectants. This study evaluated the protective effects of Prunella vulgaris L. (Labiatae) and its main phenolic acid component, rosmarinic acid (RA), against UVA-induced changes in a human keratinocyte cell line (HaCaT). Human keratinocytes exposed to UVA (10-30 J/cm(2)) were treated with an extract of P. vulgaris (1-75 mg/l) or RA (0.9-18 mg/l) for 4h. P. vulgaris and RA exhibited ability to reduce the UVA-caused decrease in a cell viability monitored by neutral red retention and by LDH release into medium. The P. vulgaris extract and RA significantly suppressed UVA-induced ROS production, which manifests as a decrease in intracellular lipid peroxidation, elevation of ATP and reduced glutathione. Post-treatment with P. vulgaris extract and RA also significantly reduced DNA damage. In addition, UVA-induced activation of caspase-3 was inhibited by treatment with P. vulgaris and RA. The P. vulgaris extract and RA demonstrated a concentration-dependent photoprotection (maximum at 25-50 mg/l and 9 mg/l, respectively). These results suggest that P. vulgaris and RA, used in skin care cosmetics, may offer protection against UVA-induced oxidative stress and may be beneficial as a supplement in photoprotective dermatological preparations.

• MeSH
• apoptóza účinky léků   účinky záření   MeSH
• buněčné linie MeSH
• cinnamáty farmakologie   MeSH
• depsidy MeSH
• fotobiologie MeSH
• keratinocyty cytologie   účinky léků   metabolismus   účinky záření   MeSH
• kyselina rozmarýnová MeSH
• lidé MeSH
• oxidační stres účinky léků   účinky záření   MeSH
• poškození DNA účinky léků   MeSH
• proliferace buněk účinky léků   účinky záření   MeSH
• Prunella * MeSH
• radioprotektivní látky farmakologie   MeSH
• rostlinné extrakty farmakologie   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cinnamáty MeSH
• depsidy MeSH
• radioprotektivní látky MeSH
• rostlinné extrakty MeSH

Periodontitis is a chronic disease associated with inflammation of the tooth-supporting tissues. The inflammation is initiated by a group of gram-negative anaerobic bacteria. These express a number of irritating factors including a lipopolysaccharide (LPS), which plays a key role in periodontal disease development. Plant extracts with anti-inflammatory and anti-microbial properties have been shown to inhibit bacterial plaque formation and thus prevent chronic gingivitis. In this study we tested effects of Prunella vulgaris L. extract (PVE; 5, 10, 25microg/ml) and its component rosmarinic acid (RA; 1microg/ml) on LPS-induced oxidative damage and inflammation in human gingival fibroblasts. PVE and RA reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. Treatment with PVE and RA also inhibited LPS-induced up-regulation of interleukin 1beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and suppressed expression of inducible nitric oxide synthase (iNOS). The results indicate that PVE and RA are able to suppress LPS-induced biological changes in gingival fibroblasts. The effects of PVE and RA are presumably linked to their anti-inflammatory activities and thus use of PVE and RA may be relevant in modulating the inflammation process, including periodontal disease.

• MeSH
• antagonismus léků MeSH
• antioxidancia analýza   farmakologie   MeSH
• cinnamáty analýza   farmakologie   MeSH
• depsidy analýza   farmakologie   MeSH
• fibroblasty účinky léků   metabolismus   patologie   MeSH
• gingiva účinky léků   metabolismus   patologie   MeSH
• glutathion metabolismus   MeSH
• kultivované buňky MeSH
• kyselina rozmarýnová MeSH
• lidé MeSH
• lipopolysacharidy antagonisté a inhibitory   toxicita   MeSH
• oxidační stres účinky léků   MeSH
• Prunella chemie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• cinnamáty MeSH
• depsidy MeSH
• glutathion MeSH
• lipopolysacharidy MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty MeSH

This paper describes a sensitive isocratic HPLC/ECD method developed for the determination of rosmarinic acid (RA) in plant material, animal feed, and pig plasma. The plasma sample preparation only includes protein precipitation and adjustment of the pH. The applicability of the method was tested on plasma samples of pigs that were exposed to a 91-day oral intake of RA via feed enriched by aerial parts of Prunella vulgaris. The plasma was directly analyzed using the method described as well as after enzymatic hydrolysis. When no hydrolysis step was included, RA and caffeic acid (CA) were quantified in the plasma. In hydrolyzed plasma samples, several other metabolites were determined, including dihydrocaffeic, ferulic, and dihydroferulic acid. The dual-channel coulometric detection employed, as an alternative to mass spectrometry, offers good selectivity and sensitivity owing to the electrochemical properties of the phenolic constituents.

• MeSH
• cinnamáty analýza   krev   metabolismus   MeSH
• depsidy analýza   krev   metabolismus   MeSH
• fortifikované potraviny analýza   MeSH
• krmivo pro zvířata analýza   MeSH
• kyselina rozmarýnová MeSH
• prasata krev   MeSH
• Prunella chemie   MeSH
• senzitivita a specificita MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cinnamáty MeSH
• depsidy MeSH

Solar radiation is a very important exogenous factor in skin pathogenesis and can lead to the development of a number of skin disorders. UVB irradiation is known to induce oxidative stress, inflammation and especially DNA lesions in exposed cells. It is important, therefore, to identify agents that can offer protection against UVB-caused skin damage. Natural compounds have been studied for their possible ability to control/modulate various lifestyle-related diseases. The application of plant compounds/extracts with screening, antioxidant and anti-inflammatory activities may also successfully protect the skin against UV-caused injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295-315 nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and post-treatment of HaCaT cells with PVE (5-50 mg/l) and RA (0.18-1.8 mg/l) reduced breakage together with the apoptotic process. PVE and RA also significantly eliminated ROS production and diminished IL-6 release. Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs to be demonstrated in vivo.

• MeSH
• antioxidancia farmakologie   MeSH
• apoptóza účinky léků   účinky záření   MeSH
• buněčná membrána účinky léků   účinky záření   MeSH
• cinnamáty farmakologie   MeSH
• depsidy farmakologie   MeSH
• interleukin-6 metabolismus   MeSH
• keratinocyty účinky léků   metabolismus   patologie   účinky záření   MeSH
• kyselina rozmarýnová MeSH
• lidé MeSH
• nadzemní části rostlin MeSH
• oxidační stres účinky léků   účinky záření   MeSH
• poškození DNA účinky léků   MeSH
• přípravky chránící proti slunci farmakologie   MeSH
• proliferace buněk účinky léků   účinky záření   MeSH
• Prunella * MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty farmakologie   MeSH
• transformované buněčné linie MeSH
• ultrafialové záření * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• cinnamáty MeSH
• depsidy MeSH
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• přípravky chránící proti slunci MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty MeSH

The chemoprotective effects of caffeic (CA), chlorogenic (CHA) and rosmarinic (RA) acids were tested against the toxicity of doxorubicin (DOX) in neonatal rat cardiomyocytes and the iron-dependent DOX induced lipid peroxidation of heart membranes, mitochondria and microsomes. The protectivity of these acids was compared with dexrazoxan, used as an adjuvant during DOX chemotherapy. The cytoprotective effects were assessed by enzyme (LDH and ASAT) and troponin I leakage, secondly by intracellular ATP content. All hydroxycinnamic acids proved non-cytotoxic, and they stabilized both membranes and the energetic status of cardiomyocytes. After preincubation of cardiomyocytes with the test compounds (100, 200 microm; 1 h) the cardiomyocytes were treated with the toxic agent, DOX (100 microm; 8 h). The test compounds protected cardiomyocytes against DOX induced oxidative stress (RA > CHA > or = CA) on all monitored parameters. Substantial preservation of monolayer integrity of the cardiomyocytes by test compounds was also found microscopically. All the acids were more effective in the assays used than dexrazoxan. RA showed the most effective cytoprotectivity. All the acids significantly reduced the iron-dependent DOX induced lipid peroxidation of heart membranes, although of the test compounds, CHA was found to be the most effective (IC(50) = 8.04 +/- 0.74/6.87 +/- 0.52 micro m for microsomes/mitochondria).

• MeSH
• cinnamáty aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• depsidy MeSH
• doxorubicin MeSH
• fytoterapie * MeSH
• inhibiční koncentrace 50 MeSH
• kardiomyocyty účinky léků   enzymologie   MeSH
• krysa rodu Rattus MeSH
• kyselina chlorogenová aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• kyselina rozmarýnová MeSH
• kyseliny kávové aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• léčivé rostliny * MeSH
• mikrozomy účinky léků   MeSH
• myokard cytologie   enzymologie   MeSH
• nemoci srdce chemicky indukované   patologie   prevence a kontrola   MeSH
• ochranné látky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• rostlinné extrakty aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• srdeční mitochondrie účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cinnamáty MeSH
• depsidy MeSH
• doxorubicin MeSH
• kyselina chlorogenová MeSH
• kyseliny kávové MeSH
• ochranné látky MeSH
• rostlinné extrakty MeSH

The cardioprotective effect of Prunella vulgaris ethylacetate fraction (PVEF) and its constituent rosmarinic acid (RA) was evaluated on isolated rat cardiomyocytes subjected to doxorubicin-induced oxidative stress. The cytoprotectivities of PVEF and RA were concentration-dependent in the range of 0.005 to 0.05 mg/ml and the effect of PVEF correlated with the RA content. Dexrazoxan (DE), used as positive control, was less effective than PVEF or RA.

• MeSH
• cinnamáty aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• depsidy MeSH
• doxorubicin MeSH
• fytoterapie * MeSH
• kardiomyocyty účinky léků   MeSH
• kardiotonika aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• kyselina rozmarýnová MeSH
• oxidační stres * MeSH
• potkani Sprague-Dawley MeSH
• protinádorová antibiotika MeSH
• Prunella * MeSH
• rostlinné extrakty aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cinnamáty MeSH
• depsidy MeSH
• doxorubicin MeSH
• kardiotonika MeSH
• protinádorová antibiotika MeSH
• rostlinné extrakty MeSH

Natural antioxidants, like phenolic acids, possess a unique chemical space that can protect cellular components from oxidative stress. However, their polar carboxylic acid chemotype reduces full intracellular antioxidant potential due to limited diffusion through biological membranes. Here, we have designed and developed a new generation of hydrophobic turn-on fluorescent antioxidant precursors that upon penetration of the cell membrane, reveal a more polar and more potent antioxidant core and simultaneously become fluorescent allowing their intracellular tracking. Their activation is stimulated by polarity alteration by sensing intracellular signals and specifically biothiols. In our design, the carboxylic group of phenolic acids that originally restricts cell entrance is derivatized and conjugated through Copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) to a coumarin derivative that its fluorescence properties are quenched with a biothiol activatable element. This more hydrophobic precursor readily penetrates cell membrane and once inside the cell the antioxidant core is revealed upon sensing glutathione, its fluorescence is restored in a turn-on manner and the generation of a more polar character traps the molecule inside the cell. This turn-on fluorescent antioxidant precursor that can be applied to phenolic acids, was developed for rosmarinic acid and the conjugate was named as RCG. The selectivity and responsiveness of RCG towards the most abundant biothiols was monitored through a variety of biophysical techniques including UV-Vis, fluorescence and NMR spectroscopy. The electrochemical behavior and free radical scavenging capacity of the precursor RCG and the active compound (RC) was evaluated and compared with the parent compound (rosmarinic acid) through cyclic voltammetry and EPR spectroscopy, respectively. The stability of the newly synthesized bioactive conjugate RC was found significantly higher than the parent rosmarinic acid when exposed to oxygen. Cell uptake experiments were conducted and revealed the internalization of RCG. The degree of intracellular DNA protection offered by RCG and its active drug (RC) on exposure to H2O2 was also evaluated in Jurkat cells.

• Klíčová slova
• DNA protection, GSH detection, Oxidative stress, ROS scavenging, Rosmarinic acid,
• MeSH
• antioxidancia * farmakologie   MeSH
• lidé MeSH
• oxidační stres MeSH
• peroxid vodíku * MeSH
• poškození DNA MeSH
• reaktivní formy kyslíku MeSH
• sulfhydrylové sloučeniny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia * MeSH
• peroxid vodíku * MeSH
• reaktivní formy kyslíku MeSH
• sulfhydrylové sloučeniny MeSH