Teresa Bobkiewicz-Kozłowska

Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain

Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain.

IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas

Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA(1)c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMA(IR) score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMA(IR), proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.

Ethanol affects acylated and total ghrelin levels in peripheral blood of alcohol-dependent rats.

There is a hypothesis that ghrelin could take part in the central effects of alcohol as well as function as a peripheral indicator of the changes which occur during long‐term alcohol consumption. The aim of this study was to determine a correlation between alcohol concentration and acylated and total form of ghrelin after a single administration of alcohol (intraperitoneal, i.p.) (experiment 1) and prolonged ethanol consumption (experiment 2). The study was performed using Wistar alcohol preferring (PR) and non‐preferring (NP) rats and rats from inbred line (Warsaw High Preferring, WHP; Warsaw Low Preferring, WLP). It was found that ghrelin in ethanol‐naive WHP animals showed a significantly lower level when compared with the ethanol‐naive WLP or Wistar rats. After acute ethanol administration in doses of 1.0; 2.0 and 4.0 g/kg, i.p., the simple (WHP) or inverse (WLP and Wistar) relationship between alcohol concentration and both form of ghrelin levels in plasma were found. Chronic alcohol intake in all groups of rats led to decrease of acylated ghrelin concentration. PR and WHP rats, after chronic alcohol drinking, had lower levels of both form of ghrelin in comparison with NP and WLP rats, respectively, and the observed differences in ghrelin levels were in inverse relationship with their alcohol intake. In conclusion, it is suggested that there is a strong relationship between alcohol administration or intake, ethanol concentration in blood and both active and total ghrelin level in the experimental animals, and that ghrelin plasma concentration can be a marker of alcohol drinking predisposition.

Advancing the delivery of anticancer drugs: Conjugated polymer/triterpenoid composite.

Exemplifying the synergy of anticancer properties of triterpenoids and ion retention qualities of conjugated polymers, we propose a conducting matrix to be a reservoir of anticancer compounds. In this study, poly(3,4-ethylenedioxythiophene), PEDOT, based matrix for electrically triggered and local delivery of the ionic form of anticancer drug, oleanolic acid (HOL), has been investigated. An initial, one-step fabrication procedure has been proposed, providing layers exhibiting good drug release properties and biological activity. Investigation of obtained systems and implementation of modifications revealed another route of fabrication. This procedure was found to yield layers possessing a significantly greater storage capacity of OL(-), as evidenced by the 52% increase in the drug concentrations attainable through electro-assisted release. Examination of the biological activity of immobilised and released OL(-) molecules proved that electrochemical treatment has negligible impact on the anticancer properties of OL(-), particularly when employing the three-step procedure, in which the range of applied potentials is limited. PEDOT/OL(-) composite has been demonstrated to be a robust and cost-effective material for controlled drug delivery.

The influence of mianserin on TNF-α, IL-6 and IL-10 serum levels in rats under chronic mild stress

BACKGROUND Antidepressants are known to affect the immunological system through mechanisms which are not completely understood. The aim of the present study was to evaluate the effect of the atypical antidepressant mianserin on the levels of tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the blood of rats in an experimental model of depression. METHODS Male Wistar rats were subjected to chronic mild stress (CMS) according to Willners method for 6 weeks. Following the development of anhedonia, the stressed and control rats (non-stressed animals) were treated with mianserin (10 mg/kg ip, twice daily) for three weeks. On the last day of the experiment, a lipopolysaccharide (LPS, 100 μg/kg ip) was injected to mianserin- or vehicle-treated rats. TNFα, IL-6 and IL-10 levels in the blood of the rats were assayed using ELISA methods. RESULTS The results indicated a significantly increased TNFα level in stressed animals when compared with the non-stressed (control) group. The levels of IL-6 and IL-10 were also elevated, especially after LPS administration. Treatment with mianserin resulted in a significant lowering of TNFα and IL-6 levels both in LPS-treated and LPS-untreated animals. There was also a decrease in IL-10 concentration in LPS-treated stressed animals. CONCLUSIONS The results confirm an increase in proinflammatory cytokines in the blood of rats with experimentally induced depression and show the protective role of the activity of mianserin on the cytokine levels, expressed in a lowering of TNFα and IL-6 levels in stressed animals, and of IL-10 levels after LPS administration.

Effect of multiple ifenprodil or spermidine treatment on social recognition in rats.

We investigated the effects of multiple (21 x) ifenprodil (1.0 mg/kg, i.p.)-[IF] and spermidine (5.0 mg/kg, i.p.)-[SP] administration on short-term memory using the social recognition test in rats. The influence of a single (lx) injection of IF and SP was also established. 1x IF or SP treatment showed a statistically insignificant tendency to impair social memory task. In contrast, 21 x SP treatment facilitated short-term memory when compared with 1x SP administration. 21x IF had no affect on the memory paradigm. The results of the present study indicate that the prolonged systemic treatment of IF or SP in relatively low doses causes no impairment of short-term memory in rats.

Reactions of N3‐Substituted Amidrazones with cis‐1,2‐Cyclohexanedicarboxylic Anhydride and Biological Activities of the Products

A series of novel compounds were synthesized in reactions of N3‐substituted amidrazones with cis‐1,2‐cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H1 NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti‐inflammatory activities were experimentally verified.

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study.

Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots.

Oleanolic Acid A-lactams Inhibit the Growth of HeLa, KB, MCF-7 and Hep-G2 Cancer Cell Lines at Micromolar Concentrations

Oleanolic acid ketones, oximes, lactams and nitriles were obtained. Complete spectral characterizations (IR, (1)H NMR, (13)C NMR, DEPT and MS) of the synthesized compounds are presented. The derivatives had oxo, hydroxyimino, lactam or nitrile functions at the C-3 position, an esterified or unmodified carboxyl group at the C- 17 location and, in some cases, an additional oxo function at the C-11 position. The new compounds were tested for cytotoxic activity on the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines with the application of MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. Among the tested compounds, some oximes and all lactams proved to be the most active cytotoxic agents. These triterpenes significantly inhibited the growth of the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines at micromolar concentrations.

Effect of Camellia sinensis extract on the expression level of transcription factors and cytochrome P450 genes coding phase I drug-metabolizing enzymes

Abstract Green tea (Camellia sinensis) is widely used as a popular beverage and dietary supplement that can significantly reduce the risk of many diseases. Despite the widespread use of green tea, the data regarding the safety as well as herb-drug interactions are limited. Therefore, the aim of our study was to assess the influence of standardized green tea extract (GTE) containing 61% catechins and 0.1% caffeine on the expression level of rat CYP genes and the corresponding transcription factors expression by realtime PCR. The findings showed that GTE resulted in a significant decrease of CYP2C6 expression level by 68% (p<0.001). In case of CYP3A1 and CYP3A2, the mRNA levels were also reduced by extract but in a lesser degree compared to CYP2C6. Simultaneously the significant increase in the mRNA level of CAR, RXR and GR factors was observed by 54% (p<0.05), 79% (p<0.001) and 23% (p<0.05), respectively after 10 days of green tea extract administration. In addition, there was noted a small increase of CYP1A1 expression level by 21% (p>0.05) was noted. No statistically significant differences were observed for CYP1A2 and CYP2D1/2. In the same study we observed an increase in amount of ARNT gene transcript by 27% (p<0.05) in the long-term use. However, green tea extract showed the ability to stimulate HNF-1α both after 3 and 10 days of treatment by 30% (p<0.05) and 80% (p<0.001), respectively. In contrast, no change was observed in the concentration of HNF-4α cDNA. These results suggest that GTE may change the expression of CYP enzymes, especially CYP2C6 (homologue to human CYP2C9) and may participate in clinically significant interactions with drugs metabolized by these enzymes. Streszczenie Zielona herbata (Camellia sinensis) jest powszechnie stosowana jako napój i suplement diety i może istotnie zmniejszać ryzyko wystąpienia wielu chorób. Pomimo powszechnego zastosowania zielonej herbaty, dane dotyczące bezpieczeństwa jak i interakcji preparatu roślinnego i leku syntetycznego są bardzo ograniczone. Celem badania była ocena wpływu standaryzowanego ekstraktu z zielonej herbaty (GTE) zawierającego 61% katechin i 0,1% kofeiny na poziom ekspresji szczurzych genów CYP i czynników transkrypcyjnych stosując technikę real-time PCR. Wyniki wykazały, że GTE znacznie obniża poziom ekspresji CYP2C6 o 68% (p<0,001). W przypadku CYP3A1 i CYP3A2 poziom mRNA tych genów był również redukowany przez ekstrakt, ale w mniejszym stopniu w porównaniu do CYP2C6. Istotny wzrost w poziomie mRNA obserwowano dla czynników CAR, RXR i GR odpowiednio o 54% (p<0,05), 79% (p<0,001) i 23% (p<0,05) po 10 dniach stosowania ekstraktu. Dodatkowo, zanotowano niewielki wzrost poziomu ekspresji CYP1A1 o 21% (p>0,05). Brak istotnych różnic zaobserwowano dla CYP1A2 i CYP2D1/2. W badaniu wykazano również wzrost ilości transkryptu genu ARNT o 27% (p<0,05) podczas dłuższego stosowania. Ponadto, ekstrakt z zielonej herbaty wykazał zdolność do stymulacji HNF-1α zarówno po 3, jak i 10 dniach trwania eksperymentu odpowiednio o 30% (p<0,05) i 80% (p<0,001). Brak zmian obserwowano w przypadku stężenia cDNA dla HNF-4α. Wyniki te sugerują, że GTE może zmieniać ekspresję enzymów CYP, szczególnie w przypadku CYP2C6 (homolog ludzki CYP2C9) i może uczestniczyć w klinicznie istotnych reakcjach z lekami metabolizowanymi przez te enzymy.