Julia Fedotova

Ropren® is a polyprenol preparation from coniferous plants that ameliorates cognitive deficiency in a rat model of beta-amyloid peptide-(25–35)-induced amnesia

This study assesses the efficacy of a fixed dose of Ropren(®) (a plant preparation isolated from the neutral fraction of an extract of spruce needles) on cognitive impairment in rats with β-amyloid peptide-(25-35)-induced amnesia. Ropren(®) was administered at a dose of 8.6mg/kg for 28 days, per os, to rats with β-amyloid peptide-(25-35)-induced amnesia. Cognitive performance was assessed using the passive avoidance paradigm and the Morris water maze and behavior was assessed using the open field test. After four weeks, Ropren(®) treatment significantly improved non-spatial and spatial learning in rats with β-amyloid peptide-(25-35)-induced amnesia. The results of the present study suggest that Ropren(®), a novel plant preparation, ameliorates cognitive deficiencies in an animal model relevant to Alzheimers disease.

Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized β-amyloid (25–35) rat model of Alzheimer's disease

The present preclinical study was designed to examine the effects of prolonged Ropren® administration (8.6 mg/kg, orally, once daily, 28 days) in a β-amyloid (25-35) rat model of Alzheimers disease following gonadectomy. The experimental model was created by intracerebroventricular injection of β-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren® was administered to the GDX rats and GDX rats treated with TP. Memory performance was assessed using the passive avoidance and the Morris water maze tests and the spontaneous locomotor activity was assessed using the open field test. Treatment with Ropren® significantly improved and restored the cognitive ability of GDX rats with β-amyloid (25-35)-induced amnesia in the passive avoidance test and Morris water maze. Co-administration of Ropren® with TP exerted a markedly synergistic memory-enhancing effect in the GDX rats with β-amyloid (25-35)-induced amnesia on the same models of memory testing. Ropren® administered alone or together with TP significantly enhanced crossing, frequency of rearing and grooming of the GDX rats with β-amyloid (25-35)-induced amnesia in the open field test. These results indicate that Ropren® has a marked memory-enhancing action in the experimental model of Alzheimers disease in male rats with altered levels of androgens.

Chili pepper as a body weight-loss food

Abstract Chili has culinary as well as medical importance. Studies in humans, using a wide range of doses of chili intake (varying from a single meal to a continuous uptake for up to 12 weeks), concluded that it facilitates weight loss. In regard to this, the main targets of chili are fat metabolism, energy expenditure, and thermogenesis. To induce weight loss, the active substance of chili, capsaicin, activates Transient Receptor Potential Cation Channel sub-family V member 1 (TRPV1) channels) receptors causing an increase in intracellular calcium levels and triggering the sympathetic nervous system. Apart from TRPV1, chili directly reduces energy expenditure by activating Brown Adipose Tissue. Weight loss by chili is also the result of an improved control of insulin, which supports weight management and has positive effects for treatment for diseases like obesity, diabetes and cardiovascular disorders. This review summarizes the major pathways by which chili contributes to ameliorating parameters that help weight management and how the consumption of chili can help in accelerating weight loss through dietary modifications.

Ropren(®) treatment reverses anxiety-like behavior and monoamines levels in gonadectomized rat model of Alzheimer's disease.

Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimers disease. New drug candidates for Alzheimers disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimers disease. Ropren® is one such candidate for the treatment of Alzheimers disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren® administration (8.6mg/kg, orally, once daily, for 28 days) on the anxiety-like behavior and monoamines levels in the rat hippocampus using a β-amyloid (25-35) rat model of Alzheimers disease following gonadectomy. Ropren® was administered to the gonadectomized (GDX) rats and GDX rats treated with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, for 28 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark test (LDT), locomotor and grooming activities were assessed in the open field test (OFT). Ropren® alone or in combination with TP-induced anxiolytic effects as evidenced in the EPM and in the LDT and increased locomotor activity in the OFT. Additionally, it was observed that dopamine (DA) and serotonin (5-HT) levels increased while 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in the hippocampus decreased. Our results indicate that Ropren® has a marked anxiolytic-like action due to an increase in the monoamines levels in the experimental rat model of Alzheimers disease with altered levels of androgens.

Anxiolytic-like effect of quinpirole in combination with a low dose of 17β-estradiol in ovariectomized rats

The aim of this study was to explore effects on anxiety-like behavior of the D2 dopamine receptor agonist, quinpirole and of the D2 dopamine receptor antagonist, sulpiride given alone or in combination with a low dose of 17β-estradiol (17β-E2) to ovariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17β-E2 (5.0 μg/rat, s.c.), quinpirole (0.1 mg/kg, i.p.), sulpiride (10.0 mg/kg, i.p.), quinpirole plus 17β-E2 or sulpiride plus 17β-E2. The animals were then tested in the black and white model (BWM) and the open field test (OFT). Quinpirole (0.1 mg/kg, i.p.) administered alone or in a combination with a low dose of 17β-E2 (5.0 μg/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM. Repeated treatment of quinpirole and 17β-E2 profoundly increased anxiolytic-like effect of the single substances they exert per se. Co-administration of quinpirole with 17β-E2 increased frequency of rearing and grooming in OVX rats in the OFT. Sulpiride (10.0 mg/kg, i.p.) treatment failed to alter anxiety-like behavior in OVX rats in the BWM. In addition, sulpiride blocked the anxiolytic-like effect of 17β-E2 in OVX rats. Application of neither sulpiride nor sulpiride plus 17β-E2 led to any changes of rearing and grooming behavior in OVX rats in the OFT. The results of the present study suggest that 17β-E2 and quinpirole interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other. Further research is needed to elucidate detailed mechanisms by which quinpirole and 17β-E2 exert synergistic effect on anxiety-related behavior.

Therapeutical strategies for anxiety and anxiety-like disorders using plant-derived natural compounds and plant extracts

Anxiety and anxiety-like disorders describe many mental disorders, yet fear is a common overwhelming symptom often leading to depression. Currently two basic strategies are discussed to treat anxiety: pharmacotherapy or psychotherapy. In the pharmacotherapeutical clinical approach, several conventional synthetic anxiolytic drugs are being used with several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being sought by researchers. The results of a plethora experimental studies demonstrated that dietary phytochemicals like alkaloids, terpenes, flavonoids, phenolic acids, lignans, cinnamates, and saponins or various plant extracts with the mixture of different phytochemicals possess anxiolytic effects in a wide range of animal models of anxiety. The involved mechanisms of anxiolytics action include interaction with γ-aminobutyric acid A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine receptors, noradrenergic and dopaminergic systems, glutamate receptors, and cannabinoid receptors. This review focuses on the use of both plant-derived natural compounds and plant extracts with anxiolytic effects, describing their biological effects and clinical application.

Involvement of D1 receptors in depression-like behavior of ovariectomized rats.

The aim of the present study was to explore the mood effects of D1 receptor agonist, SKF-38393 and D1 receptor antagonist, SCH-23390 alone or in combination with a low dose of 17β-estradiol (17β-E2) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17β-E2 (5.0 μg/rat), SKF-38393 (0.1 mg/kg), SCH-23390 (0.1 mg/kg), SKF-38393 plus 17β-E2 or SCH-23390 plus 17β-E2 for 14 days before the forced swimming test. We found that SCH-23390 significantly decreased immobility time in the OVX females. A combination of SCH-23390 with a low dose of 17β-E2 induced more profound decrease of immobility time in the OVX rats compared to the rats treated with SCH-23390 alone. On the contrary, SKF-38393 failed to modify depression-like behavior in the OVX rats. In addition, SKF-38393 significantly blocked the antidepressant-like effect of 17β-E2 in OVX rats. Thus, the D1 receptor antagonist SCH-23390 alone or in combination with a low dose of 17β-E2 exerted antidepressant-like effect in OVX female rats, while the D1 receptor agonist SKF-38393 produced depressant-like profile on OVX rats.

Testosterone promotes anxiolytic-like behavior in gonadectomized male rats via blockade of the 5-HT 1A receptors

This study was designed to examine an anxiety-like behavior in the adult gonadectomized (GDX) male rats subjected to testosterone propionate (TP) treatment alone or in combination with 8-OH-DPAT, a 5-HT1A receptor agonist, or with NAN-190, 5-HT1A receptor antagonist. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5mg/kg, s.c.), 8-OH-DPAT (0.05mg/kg, s.c.), NAN-190 (0.1mg/kg, i.p.), TP in combination with 8-OH-DPAT or NAN-190 during 14days. Anxiety behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT). 8-OH-DPAT treatment failed to modify the anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.

Different effects of vitamin D hormone treatment on depression-like behavior in the adult ovariectomized female rats

Vitamine D (VD) has important functions in the human brain and may play a role in affective-related disorders. VD receptors are expressed in multiple brain regions associated with depressive disorders. The aim of the preclinical study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0mg/kg/day,s.c., once daily, for 14days) on the depression-like behavior and corticosterone levels in the blood samples following ovariectomy in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5μg/rat,s.c., once daily, for 14days). Depression-like behavior and spontaneous locomotor activity were assessed in the forced swimming test (FST) and the open field test (OFT), respectively. The corticosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with cholecalciferol in high dose (5.0mg/kg/day,s.c.) significantly decreased the immobility time of OVX rats in the FST. Co-administration of cholecalciferol in high dose with 17β-E2 exerted a markedly synergistic antidepressant-like effect in the OVX rats on the same model of depression-like behavior testing. Cholecalciferol in high dose (5.0mg/kg/day,s.c.) administered alone or together with 17β-E2 significantly enhanced frequency of grooming for the OVX rats in the OFT. Moreover, cholecalciferol in high dose administered alone or together with 17β-E2 significantly decreased the elevated corticosterone levels in the blood serum of OVX rats following the FST. These results indicate that Cholecalciferol in high dose has a marked antidepressant-like effect in the adult female rats with low levels of estrogen.