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The study aimed to explore in vivo the influence of cannabidiol (CBD) on the development of alcohol tolerance in rats. Rats were treated with ethanol (3.0 g/kg, i.p.) and CBD (20 mg/kg, p.o.) for nine successive days, and rectal body temperature, sedation (sleeping time), and blood alcohol concentration (BAC) were measured. In the prefrontal cortex, hippocampus, and striatum, the cannabinoid (CB1R and CB2R) and dopaminergic (DRD1, DRD2, DRD4, DRD5) receptors’ mRNA level changes were analyzed using the quantitative RT-PCR method. CBD inhibited the development of tolerance to the hypothermic and sedative action of alcohol, coupled with BAC elevation. On a molecular level, the most pronounced effects of the CBD + ethanol interaction in the striatum were observed, where CBD reversed the downregulation of CB2R gene transcription caused by ethanol. For CB1R, DRD1, and DRD2 mRNAs, the CBD + ethanol interaction produced opposite effects than for CB2R ones. In turn, for the transcription of genes encoding dopaminergic receptors, the most potent effect of alcohol as CBD occurred in the hippocampus. However, the combined CBD and alcohol administration showed the same effect for each substance administered separately. Since tolerance is considered a prelude to drug addiction, obtained results allow us to emphasize the thesis that CBD can inhibit the development of alcohol dependence in rats.

Summary Introduction: The molecular basis of in vivo metabolism of selected representatives of phenylethanoids in the presence of ethanol has not been fully elucidated. Objective: The aim was to estimate a salidroside (Sal) metabolism in the liver tissue in rats with induced alcohol tolerance by assessing changes in the transcription of genes encoding cytochromes: CYP1A2, 2D2, 3A1, 2C23. Methods: cDNA was synthesized from total RNA isolated from rat liver samples. mRNA level changes were evaluated using real-time PCR (qRT-PCR) technique. Results: Ethanol caused a significant induction of the CYP1A2 and CYP2C23 genes transcription, and a decrease in the CYP3A1 mRNA level, predominantly without statistical significance. A statistically significant increase of the CYP1A2 mRNA level was observed in the group receiving only Sal (4.5 mg/kg b.w.; p.o.) (p Conclusions: There was no unequivocal effect of salidroside on the transcription of investigated cytochrome genes in the liver of rats with induced alcohol tolerance.

Summary Introduction: Blood brain barrier and multidrug resistance phenomenon are subjects of many investigations. Mainly, because of their functions in protecting the central nervous system (CNS) by blocking the delivery of toxic substances to the brain. This special function has some disadvantages, like drug delivery to the brain in neurodegenerative diseases Objective: The aim of this study was to examine how natural and synthetic substances affect the expression levels of genes (Mdr1a, Mdr1b, Mrp1, Mrp2, Oatp1a4, Oatp1a5 and Oatp1c1) that encode transporters in the blood-brain barrier. Methods: cDNA was synthesized from total RNA isolated from rat hippocampus. The expression level of genes was determined using real-time PCR (RT-PCR) method. Results: Our findings showed that verapamil, as a synthetic substance, caused the greatest reduction of mRNA level of genes studied. The standardized extract of Curcuma longa reduced the expression level for Mrp1 and Mrp2, whereas the increase of mRNA level was observed for Mdr1b, Oatp1a5 and Oatp1c1. Conclusions: These results suggests that herbal extracts may play an important role in overcoming the blood brain barrier during pharmacotherapy.

International audience; Pomegranate juice (PJ) is a rich source of ellagitannins (ETs), precursors of colonic metabolite urolithin A, which are believed to contribute to pomegranate’s neuroprotective effect. While many experimental studies involving PJ’s role in Alzheimer’s disease and hypoxic-ischemic brain injury have been conducted, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. Previously, we have reported that PJ treatment improved postural stability, which correlated well with enhancement of neuronal survival, protection against oxidative damage, and α-synuclein aggregation. Since olfactory and motor deficits are typical symptoms of PD, in this study, we aimed to investigate the capability of PJ to protect against olfactory, motoric, and neurochemical alterations. To evaluate its efficiency, Wistar rats were given a combined treatment with ROT (1.3 mg/kg b.w./day, s.c.) and PJ (500 mg/kg/day, p.o.) for 35 days. After this, we assessed the olfactory discrimination index (DI) and vertical and horizontal activities as well as levels of dopamine and its main metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) in the dissected midbrain of animals. Our findings provide the first evidence that PJ treatment protects against ROT-induced DA depletion in the midbrain, which correlates well with improved olfactory function and vertical activity as well as with the presence of urolithin A in the brain.

The aim of this study was to assess the activity of extracts from Platycodon grandiflorum A. DC (PG) in a model of chronic bronchitis in rats. The research was carried out on three water extracts: E1 &ndash, from roots of field cultivated PG, E2 &ndash, from biotransformed roots of PG, E3 &ndash, from callus of PG. The extracts differed in saponins and inulin levels&mdash, the highest was measured in E3 and the lowest in E1. Identification of secondary metabolites was performed using two complementary LC-MS systems. Chronic bronchitis was induced by sodium metabisulfite (a source of SO2). Animals were treated with extracts for three weeks (100 mg/kg, intragastrically) and endothelial growth factor (VEGF), transforming growth factors (TGF-&beta, 1, -&beta, 2, -&beta, 3), and mucin 5AC (MUC5AC) levels were determined in bronchoalveolar lavage fluid, whereas C reactive protein (CRP) level was measured in serum. Moreover, mRNA expression were assessed in bronchi and lungs. In SO2-exposed rats, an elevation of the CRP, TGF-&beta, 1, TGF-&beta, 2, VEGF, and mucin was found, but the extracts&rsquo, administration mostly reversed this phenomenon, leading to control values. The results showed a strong anti-inflammatory effect of the extracts from PG.

Summary Introduction: Rhodiola rosea (RR) and Rhodiola kirilowii (RK) are well known for their influence on central nervous system, however their impact on the development of alcohol tolerance has not yet been proven. Objective: The aim of this study was to determine the ability of RR and RK roots extracts to inhibit the development of alcohol tolerance in vivo, both, peripheral (metabolic) and central ones. Methods: Male Wistar rats were treated with RR and RK extracts (p.o.) and ethanol (i.p.) for ten consecutive days. On the first, third, fifth and eighth days the hypothermic action of ethanol was measured, while on the ninth day the loss of righting reflex was examined. On the tenth day rats were treated with assigned extract and sacrificed 1 h after the ethanol injection. Results: Both extracts inhibited development of tolerance to the hypothermic action of ethanol. The observed effect seems to be specific since none of the extracts affected body temperature in water-treated animals. RK extract also prolonged the hypnotic action of ethanol. RR-treated rats had higher blood-ethanol concentrations, in contrast to RK ones. Conclusions: RR and RK extracts inhibited the development of tolerance to the hypothermic action of ethanol. Prolongation of the hypnotic action of ethanol by RK extract may be associated with influence on the central nervous system, while the RR one also inhibited the development of metabolic tolerance.

Summary Introduction: In recent years, the search for potential neuroprotective properties of salidroside and its ability to influence the activity of nervous system become the subject of intense studies of many research groups. None of these studies, however, include an attempt to determine the effect of salidroside on the course of alcohol tolerance in vivo. Objective: The aim of this study was to investigate the ability of salidroside to inhibit the development of alcohol tolerance in rats, determining whether the effect of its action may occur in a dose-dependent manner, reducing both metabolic and central tolerance without affecting body temperature in control rats. Methods: Male Wistar rats were injected daily with ethanol at a dose of 3 g/kg for 9 consecutive days to produce ethanol tolerance. Salidroside in two doses (4.5 mg/kg and 45 mg/kg b.w.) or vehiculum was administered orally. On the 1st, 3rd, 5th and 8th day a hypothermic effect of ethanol was measured, while the loss of righting reflex procedure was performed on the 2nd, 4th, 6th and 7th day. On the 9th day rats were treated with salidroside, sacrificed 1 h after ethanol injections and blood was collected for blood-ethanol concentration measurement. Results: Salidroside at a dose of 45 mg/kg inhibited the development of tolerance to hypothermic and sedative effects of ethanol, whereas insignificant elevation of blood-ethanol concentration was observed. The dose of 4.5 mg/kg b.w. had minimal effect, only small inhibition of tolerance to hypothermic action was observed. Salidroside affected neither body mass growth nor body temperature in non-alcoholic (control) rats. Conclusions: Results of the study indicate that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the central nervous system. A comprehensive explanation of the abovementioned observations requires further pharmacological and pharmacodynamic studies.

Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate&rsquo, s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate&rsquo, s effects against Parkinson&rsquo, s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites&mdash, urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and &alpha, synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and &alpha, synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.

Neuropathic pain is a type of chronic pain caused by a lesion or disease of the somatosensory nervous system. Current therapy for this pain includes the use of pharmacological and nonpharmacological methods but due to the fact that a lot of therapy does not produce the analgesic results, it is necessary to search for new and more effective pharmacological strategy in relief of this type of pain. One of the interesting natural sources of compounds against this type of pain is extract of Cannabis sativa without psychotropic cannabinoids. Medicinal properties of C. sativa have been explored for centuries. It is well established that active compounds of this herb act through two cannabinoid receptors (CB1, CB2) as endocannabinoid system in the central nervous system. The present review addresses the recent advances in the study of pharmacological mechanisms on cellular and receptor level underlying non-hallucinogenic cannabinoid analgesic effect. In recent years, results of studies allow to state that special plant extract of C. sativa (without psychotropic cannabinoids) may be a promising source of drug used to relieve neuropathic pain.