Thirty-one of sixty dyspeptic patients tested positive for Helicobacter pylori colonization in this study, as determined by histopathology and 16S rRNA. The cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes were found in 67.7 and 93.5% of H. pylori patients, respectively. The cagA gene was found to be associated with 100% of patients with duodenal erosion and ulceration identified via endoscopy examination. In addition, 86.7% of patients with cancerous and precancerous lesions, glandular atrophy, and intestinal metaplasia identified via histopathology examination. The vacA s1m1 mutation was associated with more severe forms of gastric erosion and ulceration, as well as the presence of precancerous and cancerous lesions. Eighteen (64.3%) of the twenty-eight isolates were classified as multi-drug resistant (MDR) or pan-drug resistant (PDR) H. pylori. Due to a resurgence of interest in alternative therapies derived from plants as a result of H. pylori resistance to the majority of commonly used antibiotics, the inhibitory activity of five essential oils extracted from some commonly used medicinal plants was evaluated in vitro against drug-resistant H. pylori clinical isolates. Cinnamomum zeylanicum essential oil demonstrated the highest anti-H. pylori activity when compared to the other essential oils tested. Cinnamaldehyde was the most abundant compound in C. zeylanicum (65.91%). The toxicological evaluation established the safety of C. zeylanicum oil for human use. As a result, C. zeylanicum essential oil may represent a novel antibacterial agent capable of combating drug-resistant H. pylori carrying cytotoxin genes.
BACKGROUND: Recent discoveries in cancer therapeutics have proven combination therapies more effective than individual drugs. This study describes the efficacy of the combination of Cinnamomum zeylanicum and doxorubicin against benzene-induced leukemia. METHODS AND RESULTS: Brine shrimp assay was used to assess the cytotoxicity of C. zeylanicum, doxorubicin and their combination. After AML induction in Sprague Dawley rats, the same drugs were given to rat groups. Changes in organ weight, haematological profile, and hepatic enzymes were determined. Real-time PCR was used to elucidate the effect on the expression of STMN1, GAPDH, P53 and various TRAIL and NF-kappaB components. C. zeylanicum reduced the cytotoxicity of doxorubicin. The combination treatment showed better anti-leukemic results than any of the individual drugs as evident from STMN1 expression (p < 0.001). It was particularly effective in reducing total white blood cell counts and recovering lymphocytes, monocytes and eosinophils along with hepatic enzymes ALT and AST (p < 0.001). All doses recovered relative organ weights and improved blood parameters. The combination therapy was particularly effective in inducing apoptosis, inhibition of proliferation marker GAPDH (p < 0.001) and NF-kappaB pathway components Rel-A (p < 0.001) and Rel-B (p < 0.01). Expressions of TRAIL components c-FLIP (p < 0.001), TRAIL ligand (p < 0.001) and caspase 8 (p < 0.01) were also altered. CONCLUSION: Cinnamomum zeylanicum in combination with doxorubicin helps to counter benzene-induced cellular and hepatic toxicity and improves haematological profile. The anti-leukemic effects are potentially due to inhibition of GAPDH and NF-kappa B pathway, and through regulation of TRAIL pathway. Our data suggests the use of C. zeylanicum with doxorubicin to improve anti-leukemic therapeutic regimes.
- MeSH
- apoptóza MeSH
- benzen farmakologie MeSH
- doxorubicin farmakologie MeSH
- krysa rodu rattus MeSH
- leukemie * farmakoterapie MeSH
- NF-kappa B metabolismus MeSH
- oleje prchavé * farmakologie MeSH
- potkani Sprague-Dawley MeSH
- protein TRAIL metabolismus farmakologie MeSH
- skořicovník ceylonský metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- autoimunitní nemoci prevence a kontrola MeSH
- diabetes mellitus 2. typu prevence a kontrola MeSH
- fytoterapie metody MeSH
- léčivé rostliny MeSH
- lidé MeSH
- rostlinné extrakty * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- skořicovník ceylonský * MeSH
- skořicovník MeSH
- Check Tag
- lidé MeSH
Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters-ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.
- MeSH
- antitumorózní látky fytogenní aplikace a dávkování chemie farmakologie MeSH
- histony metabolismus MeSH
- krysa rodu rattus MeSH
- kůra rostlin chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- mikro RNA genetika MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie genetika metabolismus MeSH
- oleje prchavé aplikace a dávkování chemie farmakologie MeSH
- oleje rostlin aplikace a dávkování chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- skořicovník ceylonský chemie MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Cis-diammine dichloroplatinum (CDDP) is one of the most important chemotherapeutic agents for cancer treatment. Nonetheless, its notable side effect, nephrotoxicity, undermines its clinical use. The current study was undertaken to evaluate the protective potential of the aqueous extract (AEC) of Cinnamomum cassia (cinnamon) against the cytotoxic effect of CDDP in vitro and to elaborate the molecular mechanism underlying protection. METHODS: MTT assay was performed to assess viability of the normal kidney Vero cells treated with CDDP and/or AEC. Cells were stained with Coomassie blue, acridine orange and ethidium bromide to highlight morphological features of apoptosis. Caspase-3 activity, DNA fragmentation and reactive oxygen species (ROS) level were monitored to assess biochemical hallmarks of apoptosis. Quantitative RT-PCR and Western blot analyses were performed to elucidate expression of cellular molecules underlying the protective potential of AEC. RESULTS: CDDP-treated Vero cells exhibited hallmarks of apoptosis; these hallmarks were significantly suppressed in the presence of AEC. AEC did not alter activity of CDDP-induced cytotoxicity of breast and liver cancer cells. AEC treatment of Vero cells prevented CDDP-induced increased expression of mitochondrial Bax protein, release of mitochondrial cytochrome c, caspase-3 activation, DNA fragmentation and generation of ROS. AEC up-regulated expression of the cytoprotective gene (heme oxygenase (HO)-1). CONCLUSION: These findings suggest AEC has protective effects against CDDP-induced toxicity via preventing the activation of various cellular mechanisms mediating apoptotic cell death, without compromising the anticancer efficiency of CDDP. Thus, cinnamon may represent one of the most feasible ways to reduce the risk of CDDP-induced toxicity.
- MeSH
- antitumorózní látky toxicita MeSH
- apoptóza účinky léků MeSH
- Cercopithecus aethiops MeSH
- cisplatina toxicita MeSH
- cytochromy c metabolismus MeSH
- fragmentace DNA účinky léků MeSH
- fytoterapie metody MeSH
- kaspasa 3 metabolismus MeSH
- kůra rostlin * MeSH
- nemoci ledvin chemicky indukované prevence a kontrola MeSH
- protein X asociovaný s bcl-2 metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rostlinné extrakty farmakologie MeSH
- skořicovník ceylonský * MeSH
- upregulace MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause infections in children and immunocompromised adults. In the present study, the antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an extract of propolis were assessed against C. sakazakii and C. malonaticus. The effects of most of these antimicrobials have not been reported previously. Both strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool, camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon, lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory concentrations varied between 0.1 and 2.0 mg/mL. As an alternative treatment method, vapors of the volatiles were tested as an indirect treatment. Vapors of trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited both tested strains, while vapors of linalool were only active against C. sakazakii. To our knowledge, this study is the first time that the inhibitory activity of the vapors of these compounds and essential oils has been reported against Cronobacter spp.
- MeSH
- akrolein analogy a deriváty chemie farmakologie MeSH
- antibakteriální látky chemie farmakologie MeSH
- benzochinony chemie farmakologie MeSH
- Cronobacter sakazakii účinky léků MeSH
- Cronobacter účinky léků MeSH
- Cymbopogon chemie MeSH
- dobromysl (rod) chemie MeSH
- eugenol chemie farmakologie MeSH
- kafr chemie farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- monoterpeny chemie farmakologie MeSH
- oleje prchavé chemie farmakologie MeSH
- oleje rostlin chemie farmakologie MeSH
- rostlinné extrakty chemie farmakologie MeSH
- seskviterpeny chemie farmakologie MeSH
- skořicovník ceylonský chemie MeSH
- Syzygium chemie MeSH
- thymol chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- krevní glukóza * fyziologie metabolismus MeSH
- lidé MeSH
- metabolický syndrom * MeSH
- potraviny a nápoje * MeSH
- potraviny využití MeSH
- preference v jídle MeSH
- prodejní automaty na potraviny MeSH
- sacharidy * aplikace a dávkování farmakologie škodlivé účinky toxicita MeSH
- skořicovník ceylonský * metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- česnek metabolismus MeSH
- chrom metabolismus terapeutické užití MeSH
- diabetes mellitus 2. typu * dietoterapie MeSH
- hypoglykemika MeSH
- lidé MeSH
- metabolický syndrom terapie MeSH
- psyllium terapeutické užití MeSH
- rostlinné extrakty MeSH
- skořicovník ceylonský metabolismus MeSH
- ženšen metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- chrom terapeutické užití MeSH
- diabetes mellitus 2. typu * terapie MeSH
- dospělí MeSH
- klinické zkoušky jako téma statistika a číselné údaje MeSH
- krevní glukóza účinky léků MeSH
- kyselina lipoová terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- potravní doplňky * MeSH
- rostlinné extrakty terapeutické užití MeSH
- senioři MeSH
- skořicovník ceylonský MeSH
- triglyceridy krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- inzerce MeSH
