Marrubium vulgare Extract Improves Spatial Working Memory and Oxidative Stress Damage in Scopolamine-Treated Rats.

Background: The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions. Objective: The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia. Methods: Male Wistar rats (200-250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored. Results: Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex. Conclusions: M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention.

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia.

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

Antioxidant and Antitumor Potential of Micropropagated Balkan Endemic Sideritis scardica Griseb.

Sideritis scardica Griseb. is a critically endangered Balkan endemic species, known for its antioxidant, neuroprotective and anti-inflammatory properties. The aim of the present study was to detail an efficient protocol for the micropropagation of S. scardica. In vitro cultures were initiated from the shoot tips of 40 days-old in vivo seedlings and the effects of different plant growth regulator treatments were examined. A Murashige and Skoog nutrient medium (MS) containing 1 mg/L zeatin and 0.1 mg/L indole-3-acetic acid (IAA) proved to be the most efficient for shoot multiplication as it produced quality, vigorous shoots with a mean number of six shoots per explant. For the first time, the antioxidant and antitumor activities of extracts from in vitro-obtained plants were evaluated. In vitro cultivated plants grown in the field revealed a higher total polyphenol content (3929.1 ± 112.2 mg GAE/100 g vs. 3563.5 ± 52.8 mg GAE/100 g) and higher ORAC antioxidant activity (1211.6 ± 27.3 µmol TE/g vs. 939.9 ± 52.4 µmol TE/g) than in situ cultivated plants. A comparison of the antitumor activities of extracts from in vitro propagated shoots, field-grown in vitro-obtained plants and in situ plants on HeLa (cervical adenocarcinoma), HT-29 (colorectal adenocarcinoma) and MCF-7 (breast cancer) human cancer cell lines showed that in vitro propagated shoots had a significant concentration-dependent cytotoxic effect on the cervical adenocarcinoma cell line HeLa, while the field-grown in vitro-obtained and in situ-collected samples induced the highest reduction in the viability of the mammary carcinoma cell line MCF-7. In both cases, the cells of the control non-tumor cell line, BALB/3T3, were significantly less affected. The results showed that the in vitro multiplication protocol ensured the obtainment of numerous plants with antioxidant and antitumor potential.

Memory Recovery Effect of a New Bioactive Innovative Combination in Rats with Experimental Dementia.

Alzheimer's disease manifests as a complex pathological condition, with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease, current therapeutic strategies aim at a multitargeted approach, often relying on a combination of substances with versatile and complementary effects. In the present study, a unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, vitamin D3, selenium and an immune-supporting complex was tested in scopolamine-induced dementia in rats. Using behavioral and biochemical methods, we assessed the effects of the combination on learning and memory, and elucidated the mechanisms of these effects. Our results showed that, compared to its components, the experimental combination was most efficient in improving short- and long-term memory as assessed by the step-through method as well as spatial memory as assessed by T-maze and Barnes maze underlined by decreases in AChE activity (p < 0.05) and LPO (p < 0.001), increases in SOD activity in the cortex (p < 0.05) and increases in catalase (p < 0.05) and GPx (p < 0.01) activities and BDNF (p < 0.001) and pCREB (p < 0.05) levels in the hippocampus. No significant histopathological changes or blood parameter changes were detected, making the experimental combination an effective and safe candidate in a multitargeted treatment of AD.

Antitumor and Antioxidant Activities of In Vitro Cultivated and Wild-Growing Clinopodium vulgare L. Plants.

Clinopodium vulgare L. is a valuable medicinal plant used for its anti-inflammatory, antibacterial and wound-healing properties. The present study describes an efficient protocol for the micropropagation of C. vulgare and compares, for the first time, the chemical content and composition and antitumor and antioxidant activities of extracts from in vitro cultivated and wild-growing plants. The best nutrient medium was found to be Murashige and Skoog (MS) supplemented with 1 mg/L BAP and 0.1 IBA mg/L, yielding on average 6.9 shoots per nodal segment. Flower aqueous extracts from in vitro plants had higher total polyphenol content (29,927.6 ± 592.1 mg/100 g vs. 27,292.8 ± 85.3 mg/100 g) and ORAC antioxidant activity (7281.3 ± 82.9 µmol TE/g vs. 7246.3 ± 62.4 µmol TE/g) compared to the flowers of wild plants. HPLC detected qualitative and quantitative differences in phenolic constituents between the in vitro cultivated and wild-growing plants' extracts. Rosmarinic acid was the major phenolic constituent, being accumulated mainly in leaves, while neochlorogenic acid was a major compound in the flowers of cultivated plants. Catechin was found only in cultivated plants, but not in wild plants or cultivated plants' stems. Aqueous extracts of both cultivated and wild plants showed significant in vitro antitumor activity against human HeLa (cervical adenocarcinoma), HT-29 (colorectal adenocarcinoma) and MCF-7 (breast cancer) cell lines. The best cytotoxic activity against most of the cancer cell lines, combined with the least detrimental effects on a non-tumor human keratinocyte cell line (HaCaT), was shown by the leaf (250 µg/mL) and flower (500 µg/mL) extracts of cultivated plants, making cultivated plants a valuable source of bioactive compounds and a suitable candidate for anticancer therapy.

Neurotensin(8-13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease.

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.

Effects of Sideritis scardica Extract on Scopolamine-Induced Learning and Memory Impairment in Mice.

BACKGROUND: The neurodegenerative process in Alzheimer's disease, one of the most common types of dementia worldwide, mostly affects the cholinergic neurotransmitter system and, to a lesser extent, the monoaminergic one. The antioxidant acetylcholinesterase (AChE) and triple monoamine reuptake inhibitory activity of Sideritis scardica (S. scardica) and other Sideritis species has already been reported. OBJECTIVE: To investigate the effects of S. scardica water extracts on the learning and memory processes, anxiety-like behavior, and locomotor activities in scopolamine (Sco)-induced dementia in mice. METHODS: Male Albino IRC mice were used. The plant extract was administered for 11 consecutive days in the presence or absence of Sco (1 mg/kg, i.p). The behavioural performance of the animals was evaluated by passive avoidance, T-maze, and hole-board tests. The effects of extract on AChE activity, brain noradrenalin (NA), and serotonin (Sero) content, and antioxidant status were also monitored. RESULTS: Our experimental data revealed that the S. scardica water extract caused a reduction in degree of memory impairment and anxiety-like behaviour in mice with scopolamine-induced dementia. The extract did not affect changed by the Sco AChE activity but impact reduced brain NA and Sero levels and demonstrated moderate antioxidant activity. In healthy mice we did not confirm the presence of anxiolytic-like and AChE inhibitory effects of the S. scardica water extract. The extract did not change the control Sero brain levels and reduce those of NA. CONCLUSION: S. scardica water extract demonstrated memory preserving effect in mice with scopolamine-induced dementia and deserve further attention.

New Myrtenal-Adamantane Conjugates Alleviate Alzheimer's-Type Dementia in Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal-adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer's models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs' neuroprotective properties in dementia. METHODS: Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed. RESULTS: M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus. CONCLUSION: For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment.

Beneficial Effects of Snail Helix aspersa Extract in an Experimental Model of Alzheimer's Type Dementia.

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. OBJECTIVE: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer's type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. METHODS: SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. RESULTS: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. CONCLUSION: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer's type dementia.

Neuromodulatory Mechanisms of a Memory Loss-Preventive Effect of Alpha-Lipoic Acid in an Experimental Rat Model of Dementia.

This study evaluates some of the neuromodulatory mechanisms of the memory loss preventive effect of alpha-lipoic acid (ALA) in a scopolamine (Sco)-induced rat model of Alzheimer's disease (AD) type dementia. Our results confirmed that Sco administration induces significant memory impairment, worsens exploratory behaviour and habituation, increases acetylcholinesterase (AChE) activity, and induces pathological monoamine content changes in the prefrontal cortex and hippocampus. ALA administration largely prevented Sco-induced memory impairment. It also improved exploratory behaviour and preserved habituation, and it decreased AChE activity, reversing it to control group levels, and corrected aberrant monoamine levels in the prefrontal cortex and hippocampus. According to the data available, this is the first time that ALA-induced changes in AChE and monoamine levels in the prefrontal cortex and hippocampus (brain structures related to learning and memory) have been demonstrated in a Sco-induced rat model of AD type dementia.

Neuroprotective Effects of Myrtenal in an Experimental Model of Dementia Induced in Rats.

There is growing attention on natural substances capable of stimulating the cholinergic system and of exerting antioxidant effects, as potential therapeutic agents in Alzheimer's disease (AD). The aim of the present study is to evaluate the expected neuroprotective mechanisms of myrtenal (M) in an experimental model of dementia in rats. Dementia was induced in male Wistar rats by scopolamine (Sc) administration (0.1 mg/kg for 8 days and 20.0 mg/kg on day 9). The animals were divided into 5 groups (1) Controls; (2) Sc; (3) Sc + Myrtenal (40 mg/kg), (4) Sc + Galantamine (1 mg/kg); (5) Sc + Lipoic acid (30 mg/kg). Changes in recognition memory and habituation were evaluated via the Novel Object Recognition and Open Field tests. Acetylcholinesterase (AChE) activity, ACh levels, and changes in oxidative status of the brain were measured biochemically. The histological changes in two brain regions-cortex and hippocampus, were evaluated qualitatively and quantitatively. Myrtenal improved recognition memory and habituation, exerted antioxidant effects and significantly increased ACh brain levels. Histologically, the neuroprotective capacity of myrtenal was also confirmed. For the first time, we have demonstrated the neuroprotective potential of myrtenal in an experimental model of dementia. Our study provides proof-of-concept for the testing of myrtenal, in association with standard of care treatments, in patients affected by cognitive decline.

Tyrosinyl-amantadine: A New Amantadine Derivative With an Ameliorative Effect in a 6-OHDA Experimental Model of Parkinson's Disease in Rats.

The neuroprotective capacity of newly synthesized amantadine derivative tyrosinyl-amantadine (Tyr-Am) with expected antiparkinsonian properties was evaluated in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Male Wistar rats were divided into the following groups: sham-operated (SO), striatal 6-OHDA-lesioned control group, 6-OHDA-lesioned rats pretreated for 6 days with Tyr-Am (16 mg/kg administered intraperitoneally, i.p.), and 6-OHDA-lesioned rats pretreated for 6 days with amantadine (40 mg/kg i.p.), used as a referent. On the first, second and third week post-lesion, the animals were subjected to some behavioral tests (apomorphine-induced rotation, rotarod, and passive avoidance test). The acetylcholinesterase (AChE) activity and key oxidative stress parameters including lipid peroxidation levels (LPO) and superoxide dismutase (SOD) were measured in brain homogenates. The results showed that the neuroprotective effect of Tyr-Am was comparable to that of amantadine, improving neuromuscular coordination and learning and memory performance even at a 2.5-fold lower dose. Tyr-Am demonstrated significant antioxidant properties via decreased LPO levels but had no effect on AChE activity. We can conclude that the newly synthesized amantadine derivative Tyr-Am demonstrated significant antiparkinsonian activity in a 6-OHDA experimental model.

Effects of New Galantamine Derivatives in a Scopolamine Model of Dementia in Mice.

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive functions decline, is a leading cause for dementia and currently ranked as the sixth foremost cause of death. As of present, treatment of AD is symptomatic without convincing therapeutic benefits and new, effective, therapeutic agents are pursued. Due to massive loss of cholinergic neurons and decreased acetylcholine levels, cholinesterase inhibitors like galantamine, remain the backbone of pharmacological treatment of the disease. In the present study, using behavioral and biochemical methods, four newly synthesized galantamine derivatives, Gal 34, Gal 43, Gal 44, and Gal 46, were evaluated for a beneficial effect in a scopolamine model of dementia in mice. They were designed to have all the advantages of galantamine and additionally to inhibit ß-secretase and exert favorable effects on plasma lipids. Behavioral tests included step-through inhibitory avoidance, T-maze, and the hole-board test, whereas biochemical evaluations involved assessment of acetylcholinesterase activity, brain monoamines levels, lipid peroxidation, catalase, glutathione peroxidase, and superoxide dismutase activities along with measurement of total glutathione. Results show that Gal 43, Gal 44, and, in particular, Gal 46 are especially effective in improving both short- and long-term memory and in the case of Gal 46 having a significant effect on exploratory activity as well. Although Gal 34 did not show behavioral effects as convincing as those of the other three galantamine derivatives, it demonstrated persuasive antioxidant and restorative capacities, making all four galantamine derivatives promising AD treatment agents and prompting further research, especially that in many of our studies they performed better than galantamine.

New Galantamine Derivatives with Inhibitory Effect on Acetylcholinesterase Activity.

BACKGROUND: Inhibitors of acetylcholinesterase (AChE) are used to treat many disorders, among which are neurodegenerative upsets, like Alzheimer's disease (AD). One of the limited licensed AChE inhibitors (AChEIs) used as drugs is the natural compound galantamine (Gal). OBJECTIVE: As Gal is a toxic compound, here we expose data about its four derivatives in hybrid peptide-norgalantamine molecules, which have shown 100 times lower toxicity. METHODS: Four newly synthesized galantamine derivatives have been involved in docking analysis made by Molegro Virtual Docker. Biological assessments were performed on ICR male mice. The change in short and long-term memory performance was evaluated by passive avoidance test. AChE activity and levels of main oxidative stress parameters: lipid peroxidation, total glutathione (GSH), enzyme activities of catalase (CAT), superoxide dismutase, and glutathione peroxidase were measured in brain homogenates. RESULTS: Our experimental data revealed that the new hybrid molecules did not impair memory performance in healthy mice. Two of the compounds demonstrated better than Gal AChE inhibitory activity in the brain. None of them changed the level of lipid peroxidation products, one of the compounds increased GSH levels, and all of them increased CAT enzyme activity. CONCLUSION: The new galantamine-peptide hybrids demonstrated a potential for inhibition of AChE and antioxidant activity and deserve further attention.

Beneficial Effect of Melatonin on Motor and Memory Disturbances in 6-OHDA-Lesioned Rats.

Previous evidence has shown a link between neurodegenerative diseases, including Parkinson's disease (PD), and melatonin. The data in the literature about the impact of the hormone under different experimental PD conditions are quite controversial, and its effect on memory impairment in the disease is very poorly explored. The current research was aimed at investigating the role of melatonin pretreatment on memory and motor behavior in healthy rats and those with the partial 6-hydroxydopamine (6-OHDA) model of PD. All rodents were pretreated with melatonin (20 mg/kg, intraperitoneally) for 5 days. At 24 h and 7 days after the first treatment for healthy rats, and at the second and third week post-lesion for those with PD, the animals were tested behaviorally (apomorphine-induced rotations, rotarod, and passive avoidance tests). The neurochemical levels of dopamine (DA), acetylcholine (ACh), noradrenaline (NA), and serotonin (Sero) in the brain were also determined. The results showed that in healthy animals, melatonin pretreatment had amnestic and motor-suppressive effects and did not change the levels of measured brain neurotransmitters. In animals with PD, melatonin pretreatment exerted a neuroprotective effect, manifested as a significantly decreased number of apomorphine-induced rotations, reduced number of falls in the rotarod test, and improved memory performance. The brain DA and ACh concentrations in the same animals were restored to the control levels, and those of NA and Sero did not change. Our results demonstrate a beneficial effect of melatonin on memory and motor disturbance in 6-OHDA-lesioned rats.

Emerging Neurological and Psychobiological Aspects of COVID-19 Infection.

The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million people. The spectrum of clinical manifestations observed during COVID-19 infection varies from asymptomatic to critical life-threatening clinical conditions. Emerging evidence shows that COVID-19 affects far more organs than just the respiratory system, including the heart, kidneys, blood vessels, liver, as well as the central nervous system (CNS) and the peripheral nervous system (PNS). It is also becoming clear that the neurological and psychological disturbances that occur during the acute phase of the infection may persist well beyond the recovery. The aim of this review is to propel further this emerging and relevant field of research related to the pathophysiology of neurological manifestation of COVID-19 infection (Neuro-COVID). We will summarize the PNS and CNS symptoms experienced by people with COVID-19 both during infection and in the recovery phase. Diagnostic and pharmacological findings in this field of study are strongly warranted to address the neurological and psychological symptoms of COVID-19.

Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson's Disease: A Comparative Study.

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson's disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

Preventive Effect of Two New Neurotensin Analogues on Parkinson's Disease Rat Model.

Close functional and anatomical interactions between the neurotensin (NT) and dopamine (DA) systems suggest that NT could be associated with Parkinson's Disease (PD). However, clinical use of NT is limited due to its rapid degradation. This has led to the synthesis of a number of new NT fragment 8-13 [NT(8-13)] analogues, such as NT2 and NT4, to avoid the fast biodegradation of NT. The aim of this study was to investigate the neuroprotective effects of NT2 and NT4 on an experimental model of Parkinson's disease in rats induced with 6-hydroxydopamine (6-OHDA) treatment, producing striatal lesions. Wistar male rats were divided into different groups: a sham-operated (SO) group, a striatal 6-OHDA-lesioned control group, two groups of 6-OHDA-lesioned rats treated for 5 days with NT2 or NT4 (10 mg/kg, intraperitoneally) and a NT-treated group as reference. During the first and second week post lesion the animals were subjected to a number of behavioral tests (apomorphine-induced rotations, rotarod, passive avoidance test), and brain tissue was evaluated histologically and also assessed for DA levels. The results showed that both the number of apomorphine-induced rotations and falls (rotarod test) increased in the 6-OHDA group relative to the SO group. At the same time, the 6-OHDA-treated group showed significant memory impairment, based on the to step-through test, compared to the SO group. Treatment with NT2 and NT4 significantly decreased the number of apomorphine-induced rotations and improved the memory of lesioned animals, with these NT analogues demonstrating better neuroprotective and neuromodulatory effects than NT. DA content in the brain of the PD rats treated with NT2 and NT4 increased, possibly due to attenuation of the loss of DA-ergic neurons. NT2 and NT4 were found to easily penetrate the blood-brain barrier and they showed a better stability than the reference NT neuropeptide. In conclusion, the NT approach represents an attractive strategy for the treatment of neurodegenerative disease.

Characteristics of Honey from Serpentine Area in the Eastern Rhodopes Mt., Bulgaria.

Honey samples collected during 2007-2010 from serpentine and non-serpentine localities in the Eastern Rhodopes Mt. (Bulgaria) were characterized on the basis of their pollen content by qualitative melissopalynological analysis and physicochemical composition. Water content, pH, electrical conductivity, macroelements-K, Ca, Mg, P, and microelements-As, Cd, Co, Cr, Cu, Fe, Mn, Na, Ni, Pb, and Zn were determined after the Harmonised Methods of the International Honey Commission and ICP-AES method. The results from serpentine honey samples were compared with data from bee pollen collected from the same serpentine area. Different elements have different concentrations in honey from the same botanical type even collected from the same geographical region, same locality, and same beehive but in different vegetation season. The elements Mg, Mn, Ni, and P contribute mostly for separation of the serpentine honey samples based on measured elemental concentrations and performed principal component analysis. The element concentrations were higher in bee pollen and above the permissible limits for the toxic metals Cd and Pb. No specific indicator plant species was found for identification of the geographical origin of serpentine honey in relation to the forage of bees.

Exogenous VIP limits zymosan-induced generalized inflammation (ZIGI) in mice.

Vasoactive intestinal peptide (VIP) was administered in a model of zymosan-induced generalized inflammation (ZIGI). Its beneficial action was associated with reduced TNF-alpha and increased IL-10 production, lowered levels of creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin in circulation. VIP diminished the level of RANTES and MIP-1alpha in peritoneal exudate and circulation. The neuropeptide inhibited NO release from stimulated peritoneal macrophages. Decreased spleen, liver and kidney enlargement and less pathological changes in liver were observed. The effect of VIP was attenuated by pretreatment with VIP antagonist (anti-VIP) before the induction of shock.