Tea component, epigallocatechin gallate, potentiates anticataleptic and locomotor-sensitizing effects of caffeine in mice.

Tea is the most popular beverage worldwide. Caffeine, the psychoactive principle of tea, pharmacologically interacts with several drugs and bioactive molecules. Epigallocatechin gallate (EGCG) is a major component of tea and its known interactions with caffeine make it worthwhile to further study them by investigating the influence of EGCG on the anticataleptic and locomotor-sensitizing effects of caffeine. In the present investigation, we observed that (a) administration of caffeine or EGCG alone inhibited haloperidol-induced catalepsy, a widely used animal model to study parkinsonism, and (b) a combination of caffeine and EGCG produced greater inhibition of haloperidol-induced catalepsy. Furthermore, after repeated administration of caffeine and EGCG, either alone or in combination, we observed that (c) caffeine and EGCG contrasted the sensitization of catalepsy observed after repeated haloperidol administration by significantly reducing the duration of catalepsy. Furthermore, as haloperidol-induced catalepsy was also associated with increased lipid peroxidation, we observed that (d) EGCG administration reduced striatal lipid peroxide levels in a dose-dependent manner and that (e) the combination of caffeine with EGCG was most effective in reducing haloperidol-increased striatal lipid peroxide. Finally, we observed that (f) chronic caffeine and EGCG significantly elicited locomotor sensitization and that (g) their combination resulted in significantly greater effects. In conclusion, EGCG potentiated the effects of caffeine on haloperidol-induced catalepsy and of caffeine-elicited locomotor sensitization. Overall, these observations indicate critical interactions between caffeine and EGCG in an animal model of parkinsonism and locomotor activity and suggest that tea consumption might reduce antipsychotic-induced side effects.

Effects of Withania somnifera on oral ethanol self-administration in rats.

Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited place conditioning. Here, we investigated the effect of W. somnifera roots extract (WSE) on motivation for drinking ethanol using operant self-administration paradigms. Wistar rats were trained to self-administer ethanol (10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on acquisition and maintenance, on ethanol breakpoint under a progressive-ratio schedule of reinforcement and on the deprivation effect and reinstatement of seeking behaviours. Moreover, on the basis of the recent suggestion of an involvement of GABAB receptors in WSE central effects, we studied the interaction between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self-administration was also tested. The results show that WSE reduced the acquisition, maintenance and breakpoint of ethanol self-administration. WSE also reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self-administration. These findings show that WSE, by an action that may involve GABAB receptors, impairs motivation for drinking ethanol and suggest that further investigations should be performed to determine whether W. somnifera may represent a new approach for the management of alcohol abuse.

Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice.

Withania somnifera (WS) is utilized in Ayurvedic medicine owing to its central and peripheral beneficial properties. Several studies have accrued indicating that the recreational amphetamine-related drug (+/-)- 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) targets the nigrostriatal dopaminergic system in mice, inducing neurodegeneration and gliosis, causing acute hyperthermia and cognitive impairment. This study aimed to investigate the effect of a standardized extract of W. somnifera (WSE) on MDMA-induced neurotoxicity, neuroinflammation, memory impairment and hyperthermia. Mice received a 3-day pretreatment with vehicle or WSE. Thereafter, vehicle- and WSE-pretreated mice were randomly divided into four groups: saline, WSE, MDMA alone, WSE plus MDMA. Body temperature was recorded throughout treatment, and memory performance was assessed by a novel object recognition (NOR) task at the end of treatment. Thereafter, immunohistochemistry was performed to evaluate in the substantia nigra pars compacta (SNc) and striatum the levels of tyrosine hydroxylase (TH), as marker of dopaminergic degeneration, and of glial fibrillary acidic protein (GFAP) and TMEM119, as markers of astrogliosis or microgliosis, respectively. MDMA-treated mice showed a decrease in TH-positive neurons and fibers in the SNc and striatum respectively, an increase in gliosis and body temperature, and a decrease in NOR performance, irrespective of vehicle or WSE pretreatment. Acute WSE plus MDMA counteracted the modifications in TH-positive cells in SNc, GFAP-positive cells in striatum, TMEM in both areas and NOR performance, as compared to MDMA alone, while no differences were observed as compared to saline. Results indicate that WSE acutely administered in combination with MDMA, but not as pretreatment, protects mice against the noxious central effects of MDMA.

Effects of docosanyl ferulate, a constituent of Withania somnifera, on ethanol- and morphine-elicited conditioned place preference and ERK phosphorylation in the accumbens shell of CD1 mice.

BACKGROUND: Docosanyl ferulate (DF) is a behaviourally active GABAA receptor complex (GABAAR) agonist, recently isolated from the standardized methanolic extract of Withania somnifera Dunal (WSE) root. Previous studies have shown that WSE prevents both ethanol- and morphine-dependent acquisition and expression of conditioned place preference (CPP) and stimulation of dopamine release in the nucleus accumbens shell (AcbSh). AIMS: The study aimed at determining (a) whether DF contributes to WSE's ability to affect the acquisition and expression of ethanol- and morphine-elicited CPP and, given that phosphorylation of extracellular signal-regulated kinase (pERK) in the AcbSh is involved in associative learning and motivated behaviours, (b) whether WSE and DF may affect ethanol- and morphine-induced ERKs phosphorylation in the AcbSh. METHODS: In adult male CD1 mice, DF's effects on the acquisition and expression of ethanol- and morphine-elicited CPP were evaluated by a classical place conditioning paradigm, whereas the effects of WSE and DF on ethanol- and morphine-elicited pERK in the AcbSh were evaluated by immunohistochemistry. RESULTS AND CONCLUSIONS: The study shows that DF, differently from WSE, affects only the acquisition but not the expression of ethanol- and morphine-induced CPP. Moreover, the study shows that both WSE and DF can prevent ethanol- and morphine-elicited pERK expression in the AcbSh. Overall, these results highlight subtle but critical differences for the role of GABAARs in the mechanism by which WSE affects these ethanol- and morphine-dependent behavioural and molecular/cellular responses and support the suggestion of WSE and DF for the control of different components of drug addiction.

The biologically active compound of Withania somnifera (L.) Dunal, docosanyl ferulate, is endowed with potent anxiolytic properties but devoid of typical benzodiazepine-like side effects.

BACKGROUND: Clinical and experimental studies support the therapeutic potential of Withania somnifera (WS) (L.) Dunal on anxiety disorders. This potential is attributable to components present in different plant extracts; however, the individual compound(s) endowed with specific anxiolytic effects and potential modulatory activity of the GABAA receptor complex (GABAAR) have remained unidentified until the recent isolation from a WS methanolic root extract of some GABAAR-active compounds, including the long alkyl-chain ferulic acid ester, docosanyl ferulate (DF). AIMS: This study was designed to assess whether DF (0.05, 0.25 and 2 mg/kg), similarly to diazepam (2 mg/kg), may exert anxiolytic effects, whether these effects may be significantly blocked by the benzodiazepine antagonist flumazenil (10 mg/kg) and whether DF may lack some of the benzodiazepines' typical motor, cognitive and motivational side effects. METHODS: The behavioural paradigms Elevated Plus Maze, Static Rods, Novel Object Recognition, Place Conditioning and potentiation of ethanol-induced Loss of Righting Reflex were applied on male CD-1 mice. RESULTS: Similarly to diazepam, DF exerts anxiolytic effects that are blocked by flumazenil. Moreover, at the full anxiolytic dose of 2 mg/kg, DF lacks typical benzodiazepine-like side effects on motor and cognitive performances and on place conditioning. Moreover, DF fails to potentiate ethanol's (3 g/kg) depressant activity at the ethanol-induced Loss of Righting Reflex paradigm. CONCLUSIONS: These data point to DF as an effective benzodiazepine-like anxiolytic compound that, in light of its lack of motor, mnemonic and motivational side effects, could be a suitable candidate for the treatment of anxiety disorders.

Inhibition of Morphine- and Ethanol-Mediated Stimulation of Mesolimbic Dopamine Neurons by Withania somnifera.

Morphine- and ethanol-induced stimulation of neuronal firing of ventral tegmental area (VTA) dopaminergic neurons and of dopamine (DA) transmission in the shell of the nucleus accumbens (AcbSh) represents a crucial electrophysiological and neurochemical response underlying the ability of these compounds to elicit motivated behaviors and trigger a cascade of plasticity-related biochemical events. Previous studies indicate that the standardized methanolic extract of Withania somnifera roots (WSE) prevents morphine- and ethanol-elicited conditioned place preference and oral ethanol self-administration. Aim of the present research was to investigate whether WSE may also interfere with the ability of morphine and ethanol to stimulate VTA dopaminergic neurons and thus AcbSh DA transmission as assessed in male Sprague-Dawley rats by means of patch-clamp recordings in mesencephalic slices and in vivo brain microdialysis, respectively. Morphine and ethanol significantly stimulated spontaneous firing rate of VTA neurons and DA transmission in the AcbSh. WSE, at concentrations (200-400 µg/ml) that significantly reduce spontaneous neuronal firing of VTA DA neurons via a GABAA- but not GABAB-mediated mechanism, suppressed the stimulatory actions of both morphine and ethanol. Moreover, in vivo administration of WSE at a dose (75 mg/kg) that fails to affect basal DA transmission, significantly prevented both morphine- and ethanol-elicited increases of DA in the AcbSh. Overall, these results highlight the ability of WSE to interfere with morphine- and ethanol-mediated central effects and suggest a mechanistic interpretation of the efficacy of this extract to prevent the motivational properties of these compounds.

Protective Effect of Standardized Extract of Passiflora incarnata Flower in Parkinson's and Alzheimer's Disease.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Flavonoids exert their antioxidant effects by neutralizing all types of oxidizing radicals including the superoxide and hydroxyl radicals. Passiflora incarnata Linn. (Passifloraceae) is an important plant used in Ayurveda for the treatment of various disorders of the CNS and is a rich source of flavonoids. AIM: In the present study, we investigated the antioxidant, antiparkinsonian, and memory enhancing activity of flavonoid rich n-butanol extract of P. incarnata flowers (BEPIF). MATERIALS AND METHODS: Antioxidant activity was assessed using DPPH and hydrogen peroxide scavenging assay. The antiparkinsonian activity was evaluated using haloperidol induced catalepsy and tacrine induced vacuous chewing movement and memory enhancing activity was assessed using elevated plus maze and object recognition test. STATISTICAL ANALYSIS: The results were analyzed by Analysis of Variance test followed by Dunnett's test. RESULTS: Administration of BEPIF decreased transfer latency on day 2 and 9 significantly in elevated plus maze test and showed a significant increase in discrimination index in the object recognition test which is suggestive of its cognitive improvement action. Pretreatment with BEPIF showed a significant reduction in the haloperidol induced catalepsy and the tacrine induced jaw movements which are suggestive of its antiparkinsonian activity. In DPPH and H2O2 scavenging assay, BEPIF exhibited significant free radical scavenging activity. CONCLUSIONS: It can be concluded that the butanolic extract of P. incarnata flowers has significant antiparkinsonian and cognition enhancing activity which may be associated with its antioxidant potential. Thus, P. incarnata flowers may be employed in treatment of dementia and parkinsonism.

Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn.

Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.

Protective effect of Rubia cordifolia on reserpine-induced orofacial dyskinesia.

In this study, the neuroprotective potential and in vivo antioxidant status of extract of roots and rhizomes of Rubia cordifolia L (MERC) in reserpine-induced orofacial dyskinesia was studied. Reserpine (1 mg/kg, s.c.) on day 1, 3 and 5 was used to induce orofacial dyskinesia. At the end of treatment schedule, MERC significantly inhibited reserpine-induced vacuous chewing movements, tongue protrusions, orofacial bursts, catalepsy. MERC significantly increased locomotion and rearing in open field test. MERC exhibited significant elevation in the levels of superoxide dismutase, catalase, glutathione reductase and inhibition of lipid peroxidation in forebrain region, compared with the reserpine treated group. It significantly elevated dopamine levels in the forebrain region. GCMS revealed the presence of anthraquinones, having strong antioxidant activity. It is concluded that oxidative stress might play an important role in reserpine-induced abnormal oral movements and MERC significantly protected animals against reserpine-induced orofacial dyskinesia and has great potential in treatment of neuroleptic induced orofacial dyskinesia.

Reversal of reserpine-induced orofacial dyskinesia and catalepsy by Nardostachys jatamansi.

CONTEXT: Reserpine-induced orofacial dyskinesia is an animal model of tardive dyskinesia which may be associated with neurodegeneration and free radical damage. AIM: The aim was to assess the neuroprotective potential and in vivo antioxidant status of alcoholic extract of roots and rhizomes of Nardostachys jatamansi (ANJ) and its triterpenes (TNJ) in reserpine-induced orofacial dyskinesia. MATERIALS AND METHODS: In the present study, repeated treatment with reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3, and 5) significantly induced vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats. The effect on reserpine-induced catalepsy was also studied. The effect of ANJ and TNJ on levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in the forebrain region was assessed. STATISTICAL ANALYSIS: All observations were expressed as mean ± SEM. Statistical analysis was performed by the one-way ANOVA followed by Dunnett's test. P<0.05 was regarded as statistically significant. RESULTS: At the end of the treatment schedule, ANJ and TNJ significantly inhibited reserpine-induced VCM, TP, and catalepsy, and significantly increased the locomotion and rearing in the open-field test. Treatment with ANJ and TNJ exhibited significant elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) and inhibition of lipid peroxidation (LPO) in forebrain region compared to the reserpine treated group. CONCLUSIONS: The study concludes that ANJ and TNJ significantly protected animals against reserpine-induced orofacial dyskinesia as well as catalepsy suggesting its potential value in the treatment of neuroleptic-induced orofacial dyskinesia and Parkinson's disease.

Mucuna pruriens attenuates haloperidol-induced orofacial dyskinesia in rats.

Neuroleptic-induced tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. The agents improving dopaminergic transmission improve TD. Mucuna pruriens seed contains levodopa and amino acids. The effect of methanolic extract of M. pruriens seeds (MEMP) was studied on haloperidol-induced TD, alongside the changes in lipid peroxidation, reduced glutathione, superoxide dismutase (SOD) and catalase levels. The effect of MEMP was also evaluated in terms of the generation of hydroxyl and 1,1-diphenyl,2-picrylhydrazyl (DPPH) radical. MEMP (100 and 200 mg kg⁻¹) inhibited haloperidol-induced vacuous chewing movements, orofacial bursts and biochemical changes. MEMP also inhibited hydroxyl radical generation and DPPH. The results of the present study suggest that MEMP by virtue of its free radical scavenging activity prevents neuroleptic-induced TD.

Korean ginseng extract attenuates reserpine-induced orofacial dyskinesia and improves cognitive dysfunction in rats.

Reserpine-induced orofacial dyskinesia in rats is an animal model of tardive dyskinesia that has been linked with free radical generation and oxidative stress. In the present study, reserpine (1 mg kg(-1), s.c.) was given to rats on days 1, 3 and 5 to induce orofacial dyskinesia, which is characterised by increased vacuous chewing and tongue protrusion. Sub-chronic treatment with Korean ginseng extract from day 1 to day 21 along with reserpine on days 1, 3 and 5 significantly and dose-dependently (100 and 200 mg kg(-1)) reduced reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine-treated animals also showed poor retention of memory in the elevated plus maze paradigm. The sub-chronic Korean ginseng extract administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that repeated reserpine treatment significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of rats. Reserpine-treated rats also showed decreased levels of antioxidant defence enzymes, superoxide dismutase (SOD), and catalase. Sub-chronic administration of Korean ginseng extract dose-dependently and significantly reduced lipid peroxidation and restored decreased GSH levels by repeated reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The present study concludes that oxidative stress might play an important role in reserpine-induced abnormal oral movements, and Korean ginseng extract could be useful in the treatment of drug-induced dyskinesia and amnesia.

Formulation and evaluation of telmisartan microspheres by emulsion solvent evaporation technique.

Microspheres are multi-component system provide constant and prolonged drug release. Furthermore their floating abilities increase gastric residence time. These properties reduce the gastrointestinal toxic effects and dosing frequency and thereby improve the patient compliance. The present study aimed to formulate and evaluate telmisartan microspheres. Emulsion solvent evaporation (ESE) technique was employed for microsphere preparation using different ratios of ethyl cellulose polymer and drug. Prepared microspheres were evaluated for drug entrapment efficiency, micromeritic characters, floating behaviour and in vitro drug release. This revealed polymer drug ratio has influence on drug release.

Phytopharmacological properties of coriander sativum as a potential medicinal tree: an overview.

Coriandrum Sativum family Umbelliferae is highly reputed ayurvedic medicinal tree commonly known as the Dhanyaka. It is small sized tree growing throughout India, Italy. Netherlands, Central and Eastern Europe, China and Bangladesh. The different parts of this plant contain monoterpenes, α-pinene, limpnene, γ-terpinene, p-cymene, borneol, citronellol, camphor, geraniol, coriandrin, dihydrocoriandrin, coriandronsA-E, flavonoids and essential oils. Various parts of this plant such as seed, leaves, flower and fruit, possess Diuretic, Antioxidant Activity, Ant-diabetic Anti-convulsant activity, Sedative Hypnotic Activity, Anti-microbial Activity, Anti mutagenic, Anthelmintic activity. Various phytopharmacological evaluations have been reported in this literature for the important potential of the Coriandrum sativum.

Experimental modeling of anxiety.

Anxiety has much impact on human as well as animal behaviors. For evaluation of anxiolytic drug require both clinical and biological aspect of anxiety. We review the existing experimental models of anxiety like elevated plus maze apparatus, light dark model, open field apparatus, holeborad apparatus in order to promote further understanding of neurobiological aspects of anxiety.

Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn.

Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.