This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results.
- Klíčová slova
- 3-hydroxy-3-methylglutaryl-CoA reductase, Achillea wilhelmsii, anti-hypercholesterolemic, cardiometabolic disease, docking, flavonoids, hypoglycemic, inflammation,
- MeSH
- acylkoenzym A chemie MeSH
- antioxidancia aplikace a dávkování chemie MeSH
- buněčné linie MeSH
- experimentální diabetes mellitus farmakoterapie MeSH
- fenoly aplikace a dávkování chemie izolace a purifikace MeSH
- flavonoidy aplikace a dávkování chemie izolace a purifikace MeSH
- hypercholesterolemie farmakoterapie MeSH
- hyperglykemie farmakoterapie MeSH
- lidé MeSH
- mediátory zánětu chemie MeSH
- myši inbrední NOD MeSH
- myši MeSH
- řebříček chemie MeSH
- rizikové faktory MeSH
- rostlinné extrakty aplikace a dávkování chemie MeSH
- simulace molekulového dockingu MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3-hydroxy-3-methylglutaryl-coenzyme A MeSH Prohlížeč
- acylkoenzym A MeSH
- antioxidancia MeSH
- fenoly MeSH
- flavonoidy MeSH
- mediátory zánětu MeSH
- rostlinné extrakty MeSH
OBJECTIVES: To investigate the effects of perorally administered juice on tetrachloromethane (CCl4)-induced hepatotoxicity model in rats. METHODS: Male Wistar rats were tube-administrated silymarin, Ecballium juice at 0.2 mL/kg and 0.7 mL/kg daily for 3 consequent days, i.e., 3.28 μg and 11.48 μg of cucurbitacin B per kg of body weight respectively. On the third day, liver damage was induced by intraperitoneal application of CCl4. On the fourth day, abdominal cavity was macroscopically examined and liver samples were taken for histopathological and immunochemical evaluation. HPLC was used to determine the content of the active substance cucurbitacin B. RESULTS: The experiment revealed that 0.7 ml/kg juice concentration expressed the highest pro-apoptotic activity, but with prevailing negative effects. Compared with the lower concentration, there was an observable vasodilatation with consequent interstitial hemorrhages and a larger scope of inflammatory damage, which suppressed the hepatoprotective effect. In the 0.2 mL/kg concentration, there was a smaller pro-apoptotic activity but other parameters had better results, and the liver parenchyma damage was reversible. CONCLUSIONS: No reactions confirming the potentially allergic effect on laboratory rats were observed; its hepatoprotective and anti-inflammatory effect was confirmed on a model of acute liver damage.
- Klíčová slova
- Apoptosis, Ecballium elaterium, Hepatotoxicity, Rats, Tetrachloromethane,
- Publikační typ
- časopisecké články MeSH
Clay minerals have been proposed as very useful materials for modulating drug delivery. These are the commonly used materials in pharmaceutical production both as inorganic carriers or active agents. We focused on the development of suitable long-acting material for local treatment of oral infection where clay minerals act as inorganic drug carriers. Organovermiculites with antibacterial activity were prepared by ion exchange reactions using different concentrations of chlorhexidine diacetate. The samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermal analysis (TGA). The antibacterial activity was evaluated by finding the minimum inhibitory concentration (MIC). All studied organoclays possessed good antibacterial activity after 24h exposure against Escherichia coli, Enterococcus faecalis and particularly against Staphylococcus aureus. Pseudomonas aeruginosa however proved very resistant as only the sample with the highest concentration of CA that successfully inhibited bacterial growth. Furthermore, clay mineral vermiculite was subjected to in vivo toxicological analysis and its influence on gastrointestinal tract during its oral application was investigated. Tissue samples from buccal mucosa, tongue, esophagus, stomach, terminal duodenum, small intestine, caecum, distal colon and liver were subjected to histological examination, both macroscopically and microscopically. Neither systemic nor local reactions were observed. Therefore the toxicity of vermiculite to a mammal model organism can be excluded.
- Klíčová slova
- Antibacterial activity, Histological examination, In vivo tests, Organovermiculites,
- MeSH
- antibakteriální látky chemie farmakologie toxicita MeSH
- Bacteria účinky léků MeSH
- chlorhexidin chemie farmakologie MeSH
- gastrointestinální trakt účinky léků MeSH
- krysa rodu Rattus MeSH
- nanokompozity chemie toxicita MeSH
- potkani Wistar MeSH
- silikáty hliníku chemie farmakologie toxicita MeSH
- sliznice účinky léků MeSH
- testování materiálů 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
- antibakteriální látky MeSH
- chlorhexidin MeSH
- silikáty hliníku MeSH
- vermiculite MeSH Prohlížeč
The in vitro antitumour activity studies on a panel of human cancer cell lines (A549, HeLa, G-361, A2780, and A2780R) and the combined in vivo and ex vivo antitumour testing on the L1210 lymphocytic leukaemia model were performed on the cis-[PtCl2(naza)2] complexes (1-3) involving the 7-azaindole derivatives (naza). The platinum(II) complexes showed significantly higher in vitro cytotoxic effects on cell-based models, as compared with cisplatin, and showed the ability to avoid the acquired resistance of the A2780R cell line to cisplatin. The in vivo testing of the complexes (applied at the same dose as cisplatin) revealed their positive effect on the reduction of cancerous tissues volume, even if it is lower than that of cisplatin, however, they also showed less serious adverse effects on the healthy tissues and the health status of the treated mice. The results of ex vivo assays revealed that the complexes 1-3 were able to modulate the levels of active forms of caspases 3 and 8, and the transcription factor p53, and thus activate the intrinsic (mitochondrial) pathway of apoptosis. The pharmacological observations were supported by both the histological and immunohistochemical evaluation of isolated cancerous tissues. The applicability of the prepared complexes and their fate in biological systems, characterized by the hydrolytic stability and the thermodynamic aspects of the interactions with cysteine, reduced glutathione, and human serum albumin were studied by the mass spectrometry and isothermal titration calorimetric experiments.
- MeSH
- cisplatina farmakologie MeSH
- HeLa buňky MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- imunohistochemie MeSH
- indoly chemie MeSH
- Kaplanův-Meierův odhad MeSH
- kaspasa 3 metabolismus MeSH
- kaspasa 8 metabolismus MeSH
- lidé MeSH
- lymfoidní leukemie farmakoterapie patologie MeSH
- magnetická rezonanční spektroskopie MeSH
- MFC-7 buňky MeSH
- molekulární struktura MeSH
- myši inbrední DBA MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- organoplatinové sloučeniny chemie farmakologie MeSH
- protinádorové látky chemie farmakologie MeSH
- stabilita léku MeSH
- termodynamika MeSH
- viabilita buněk účinky léků MeSH
- výsledek terapie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 7-azaindole dimer MeSH Prohlížeč
- cisplatina MeSH
- indoly MeSH
- kaspasa 3 MeSH
- kaspasa 8 MeSH
- nádorový supresorový protein p53 MeSH
- organoplatinové sloučeniny MeSH
- protinádorové látky MeSH
Various hemostatics are used for renal surgical procedures. We investigated the hemostatic efficacy of cellulose derivatives on the model of partial nephrectomy in rats focusing on the local reaction of renal parenchyma. A total of 50 Wistar rats were divided into five groups of 10 animals each. Partial nephrectomy of the caudal pole without hilar vascular control was performed. Oxidized cellulose (OC), sodium salt of oxycellulose (OCN), carboxymethyl cellulose (CMC), dialdehyde cellulose (DAC), and gelatin-based hemostatic (C) were applied to the bleeding wounds. The time to hemostasis was monitored. Half of the animals were euthanized after 3 days, the second half 30 days from the experiment start date. The left kidney was excised and subjected to histopathological examination. The biochemical data was subjected to statistical analysis. The time to hemostasis in all groups was significantly less than in the C group (in OC p = 0.0057, OCN p = 0.0039, CMC and DAC p = 0.0001). In the C group, massive hemorrhages and necrosis did occur. In the OC and OCN groups, there were regenerative changes, a receding inflammatory reaction and hemorrhage. DAC caused an immune reaction and massive interstitial hemorrhages with biochemical signs of liver damage. Parenchyma in CMC revealed a reduction of necrosis and interstitial hemorrhages with regenerative processes. The most effective hemostatics were CMC and OC, achieving the best results both in the time to hemostasis, and for histopathological evaluation.
- MeSH
- celulosa analogy a deriváty terapeutické užití MeSH
- hemostatika chemie terapeutické užití MeSH
- hemostáza účinky léků MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků patologie chirurgie MeSH
- nefrektomie * MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- celulosa MeSH
- hemostatika MeSH
The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ mass spectrometry, conductivity, DFT calculations), and studied for their in vitro cytotoxicity and in vitro and in vivo anti-inflammatory effects on LPS-activated macrophages (derived from THP-1 cell line) and using the carrageenan-induced hind paw edema model on rats. The obtained results indicate that the representative complexes (1, 3, 6) exhibit a strong ability to reduce the production of pro-inflammatory cytokines TNF-α, IL-1β and HMGB1 without influence on the secretion of anti-inflammatory cytokine IL-1RA in the LPS-activated macrophages. The complexes also significantly influence the formation of edema, caused by the intraplantar application of polysaccharide λ-carrageenan to rats in vivo. All the tested complexes showed similar or better biological effects as compared with Auranofin, but contrary to Auranofin they were found to be less cytotoxic in vitro. The obtained results clearly indicate that the gold(I) complexes behave as very effective anti-inflammatory agents and could prove to be useful for the treatment of difficult to treat inflammatory diseases such as rheumatoid arthritis.
- MeSH
- akutní monocytární leukemie MeSH
- antiflogistika nesteroidní chemická syntéza chemie farmakologie MeSH
- cytokiny krev MeSH
- cytotoxiny chemická syntéza chemie farmakologie MeSH
- edém chemicky indukované farmakoterapie metabolismus patologie MeSH
- karagenan MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- krysa rodu Rattus MeSH
- kvantová teorie MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- makrofágy účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- potkani Wistar MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zlato * 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
- Názvy látek
- antiflogistika nesteroidní MeSH
- cytokiny MeSH
- cytotoxiny MeSH
- karagenan MeSH
- komplexní sloučeniny MeSH
- lipopolysacharidy MeSH
- puriny MeSH
- zlato * MeSH
Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.
- MeSH
- cytoprotekce účinky léků MeSH
- experimentální diabetes mellitus farmakoterapie MeSH
- flavanony izolace a purifikace farmakologie MeSH
- myši MeSH
- ovoce chemie MeSH
- scavengery volných radikálů izolace a purifikace farmakologie MeSH
- Scrophulariaceae chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flavanony MeSH
- scavengery volných radikálů MeSH
The hybrid sterility-1 (Hst1) locus at Chr 17 causes male sterility in crosses between the house mouse subspecies Mus musculus domesticus (Mmd) and M. m. musculus (Mmm). This locus has been defined by its polymorphic variants in two laboratory strains (Mmd genome) when mated to PWD/Ph mice (Mmm genome): C57BL/10 (carrying the sterile allele) and C3H (fertile allele). The occurrence of sterile and/or fertile (wild Mmm x C57BL)F1 males is evidence that polymorphism for this trait also exists in natural populations of Mmm; however, the nature of this polymorphism remains unclear. Therefore, we derived two wild-origin Mmm strains, STUS and STUF, that produce sterile and fertile males, respectively, in crosses with C57BL mice. To determine the genetic basis underlying male fertility, the (STUS x STUF)F1 females were mated to C57BL/10 J males. About one-third of resulting hybrid males (33.8%) had a significantly smaller epididymis and testes than parental animals and lacked spermatozoa due to meiotic arrest. A further one-fifth of males (20.3%) also had anomalous reproductive traits but produced some spermatozoa. The remaining fertile males (45.9%) displayed no deviation from values found in parental individuals. QTL analysis of the progeny revealed strong associations of male fitness components with the proximal end of Chr 17, and a significant effect of the central section of Chr X on testes mass. The data suggest that genetic incompatibilities associated with male sterility have evolved independently at the proximal end of Chr 17 and are polymorphic within both Mmd and Mmm genomes.
- MeSH
- epididymis abnormality patologie MeSH
- lokus kvantitativního znaku MeSH
- mužská infertilita genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- polymorfismus genetický * MeSH
- savčí chromozomy genetika MeSH
- spermie abnormality MeSH
- testis abnormality patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
