Rhodiola rosea L. extract and its active compound salidroside antagonized both induction and reinstatement of nicotine place preference in mice.

Rationale: Conventional pharmacological treatments for drug addiction aim to reduce three most important aspects: withdrawal syndrome, craving, and relapse. Pharmacological treatments currently available for the treatment of tobacco smoking are able to alleviate withdrawal symptoms but are not sufficiently effective in reducing craving and rarely effective to prevent relapse. Rhodiola rosea L.

Rhodiola rosea Impairs Acquisition and Expression of Conditioned Place Preference Induced by Cocaine.

A novel approach to the treatment of adverse effects of drugs of abuse is one which makes use of natural products. The present study investigated the effect of Rhodiola rosea L. hydroalcoholic extract (RHO) on cocaine-induced hyperactivity and conditioned place preference (CPP) in mice.

Effects of Brugmansia arborea Extract and Its Secondary Metabolites on Morphine Tolerance and Dependence in Mice.

The aim of the present study was to investigate, in vivo, the effect of a Brugmansia arborea extract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in order to make them tolerant or dependent. Morphine tolerance was assessed using the tail-flick test at 1st and 5th days.

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

Rationale: Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy.

Objectives: The present study investigated the effects of a Rhodiola rosea L.

Favourable involvement of α2A-adrenoreceptor antagonism in the I₂-imidazoline binding sites-mediated morphine analgesia enhancement.

Aim of the present study was to obtain novel α(2)-adrenoreceptor (α(2)-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α(2)-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α(2A)-subtype.

Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence.

The functional in vitro study of the enantiomers of imidazolines 4-7 highlighted the role played by the nature of the ortho phenyl substituent in determining the preferred α(2C)-AR configuration. Indeed, the (S) enantiomers of 4-6 or (R) enantiomer of 7 behave as eutomers and activate this subtype as full agonists; the corresponding distomers are partial agonists. Because in clinical pain management with opioids α(2C)-AR agonists, devoid of the α(2A)-AR-mediated side effects, may represent an improvement over current therapies with clonidine like drugs, 4 and its enantiomers, showing α(2C)-agonism/α(2A)-antagonism, have been studied in vivo.

Effects of a Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice.

This study investigated the effect of Rhodiola rosea L. extract on acquisition and expression of morphine tolerance and dependence in mice. Therefore animals were injected with repeated administration of morphine (10 mg/kg, subcutaneous) twice daily for five or six days, in order to make them tolerant or dependent.

Novel highly potent and selective sigma 1 receptor antagonists related to spipethiane.

Conservative chemical modifications of the core structure of the lead spipethiane (1) afforded novel potent sigma(1) ligands. sigma(1) affinity and sigma(1/)sigma(2) selectivity proved to be favored by the introduction of polar functions (oxygen atom or carbonyl group) in position 3 or 4 (4-6) or by the elongation of the distance between the two hydrophobic portions of the molecule with the simultaneous presence of a carbonyl group in position 4 (8 and 9). The observed cytostatic effect against the human breast cancer cell line MCF-7/ADR, highly expressing sigma(1) receptors, and not against MCF-7, as well as the enhancement of morphine analgesia highlighted the sigma(1) antagonist profile of this series of compounds.

Evaluation of Rhodiola rosea L. extract on affective and physical signs of nicotine withdrawal in mice.

The aim of the present study was to investigate the effects of a Rhodiola rosea L. extract on the prevention of the development of nicotine dependence and for the reduction of abstinence suffering following nicotine cessation in mice. Dependence was induced in mice by subcutaneous injections of nicotine (2 mg/kg, 4 times/day) for eight days.

Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine?

The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided alpha(2)-adrenergic (AR) ligands endowed with significant alpha(2C)-agonism/alpha(2A)-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine.

Novel ligands rationally designed for characterizing I2-imidazoline binding sites nature and functions.

The study of two series of 2-aryl-ethylen-imidazolines 3-7 and 8-12 inspired by I2-IBS ligands phenyzoline (1) and diphenyzoline (2), respectively, confirmed the interesting "positive" or "negative" morphine analgesia modulation displayed by their corresponding leads and demonstrated that these effects might be correlated with morphine tolerance and dependence, respectively. By comparative examination of rationally designed compounds, some analogies between binding site cavity of I2-IBS proteins and alpha 2C-adrenoreceptor emerged.

Thiorphan-induced survival and proliferation of rat thymocytes by activation of Akt/survivin pathway and inhibition of caspase-3 activity.

The activity of substance P (SP) in the rat thymus seems to be tightly controlled by its bioavailability. In this study, we provide evidence for the expression of the SP-degrading enzyme, neutral endopeptidase (NEP)/CD10, by rat thymocyte subsets, and we illustrate its involvement in the in vivo SP/neurokinin-1 receptor (NK(1)R)-mediated regulation of thymocyte survival and proliferation. NEP/CD10 was expressed at both mRNA and protein levels on a substantial portion (45.

Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats.

Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R.

Synthesis, docking studies and anti-inflammatory activity of 4,5,6,7-tetrahydro-2H-indazole derivatives.

A regioselective synthesis of 2,3-disubstituted tetrahydro-2H-indazols, mediated by alpha-zirconium sulfophenylphosphonate-methanephosphonate, was reported. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. Two lead derivatives were chosen endowed with good binding energies and good ADME profiling.

Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats.

Rhodiola rosea L. is one of the most popular adaptogen and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system.

Involvement of I2-imidazoline binding sites in positive and negative morphine analgesia modulatory effects.

Some studies, suggesting the involvement of I(2)-imidazoline binding sites (I(2)-IBS) in morphine analgesia modulation, prompted us to examine on mice antinociceptive assays the effect produced by 1 (phenyzoline), that in view of its high I(2)-IBS affinity and high I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors might be considered the first interesting I(2)-IBS ligand. The study was also applied to its ortho phenyl derivative 2 (diphenyzoline), designed and prepared in order to produce a possible modification of the biological profile of 1. Diphenyzoline (2) retains a significant I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors.

Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice.

Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R.

Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats.

Rationale: It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption.

Objectives: The aims of the present study were (1) to evaluate the role of the endocannabinoid system in the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role.

Methods: Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions.

Reduction of ethanol intake by chronic treatment with Hypericum perforatum, alone or combined with naltrexone in rats.

Acute treatment with extracts of Hypericum perforatum, the common plant usually called St. John's Wort, reduces voluntary ethanol intake in Marchigian Sardinian alcohol-preferring (msP) rats and acts synergistically with opioid receptor antagonists to further attenuate ethanol consumption. The present study evaluated the effect of chronic (once a day for 12 days) intragastric administration of a CO2 Hypericum perforatum extract (HPCO2), given alone or combined with naltrexone (NTX), on ethanol intake offered 2h/day in msP rats.

Effect of Hypericum perforatum CO2 extract on the motivational properties of ethanol in alcohol-preferring rats.

Aims: Extracts of Hypericum perforatum (HPE) attenuate voluntary ethanol intake in different lines of alcohol-preferring rats. The present study evaluated the effect of the intragastric (IG) administration of a CO(2) Hypericum perforatum extract (HPCO(2)) on operant ethanol self-administration, as well as on voluntary ethanol intake, after a period of ethanol deprivation in genetically selected Marchigian Sardinian alcohol-preferring rats.

Methods: HPCO2 was administered by means of an indwelling IG catheter, 1 h before the tests.

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death.

Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots.

Hypericum perforatum methanolic extract inhibits growth of human prostatic carcinoma cell line orthotopically implanted in nude mice.

The antiproliferative effect of serotonin-reuptake inhibitors (SSRI) and serotonin antagonists has been demonstrated in prostate tumors. Since Hypericum perforatum components act as serotonin-reuptake inhibitors and exert cytotoxic effects on several human cancer cell lines, in this work we analyzed the effect of a treatment with Hypericum perforatum extract (HPE) on the growth of human prostate cancer cells in vitro and in vivo. This study highlighted a significant reduction of tumor growth and number of metastasis suggesting that this natural compound may be useful in the treatment of prostate cancer.

Neonatal capsaicin treatment affects rat thymocyte proliferation and cell death by modulating substance P and neurokinin-1 receptor expression.

Herein we provide evidence that substance P (SP) and its neurokinin-1 receptor (NK-1R) expressed on thymocytes counteract thymus depletion induced by neonatal capsaicin (CPS) treatment by affecting thymocyte proliferation and apoptotic death. SP administration reversed the CPS-mediated inhibitory effects on the total thymocyte number and subset distribution, namely CD4+ and CD4- CD8- cells, through its interaction with NK-1R as shown by concomitant NK-1R (SR140333) antagonist administration. SP-induced enhancement of thymus cellularity parallels its ability of inhibiting the thymocyte apoptotic program.

Hypericum perforatum CO2 extract and opioid receptor antagonists act synergistically to reduce ethanol intake in alcohol-preferring rats.

Background: Hypericum perforatum extracts attenuate ethanol intake in alcohol-preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce ethanol intake in rats and humans. The combination of different agents that reduce ethanol intake has been proposed as an approach to the pharmacotherapy of alcoholism.

Plant derivatives in the treatment of alcohol dependency.

The present review summarizes the findings of the effects of extracts of purified compounds from several plants on alcohol intake in alcohol-preferring rats. These include St. John's wort (Hypericum perforatum, HPE), kudzu (Pueraria lobata) and ibogaine (Tabernanthe iboga).