Effect of curcumin against pentylenetetrazol-induced seizure threshold in mice: possible involvement of adenosine A1 receptors.

Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20-120 mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80 mg/kg) was prevented by 8-phenyltheophylline (0.5 mg/kg, i.p., non-selective adenosine receptor antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (5 mg/kg, i.p., adenosine A1 receptor antagonist) but not by 8-(3-cholorostryl)caffeine (4 mg/kg, i.p., adenosine A2A receptor antagonist). Further, 5'-N-ethylcarboxamidoadenosine (0.005 mg/kg, i.p., non-selective A1 /A2 receptor agonist), or N(6) -cyclohexyladenosine (0.2 mg/kg, i.p., adenosine A1 receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5'-(N-cyclopropyl) carboxamidoadenosine (0.1 mg/kg, i.p., adenosine A2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A1 but not A2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions.

Evaluation of antidepressant-like activity of novel water-soluble curcumin formulations and St. John's wort in behavioral paradigms of despair.

BACKGROUND: Curcumin is the active principle of Curcuma longa, one of the widely used components in the traditional system of medicine in India. Despite its efficacy in experimental studies aiming at neuronal disorders like depression, curcu-min's poor water solubility challenges the production of therapeutic formulations. This study investigates the antidepressant-like activity of novel water-soluble curcumin formulations, dispensed in three different concentrations. Further, the study comparatively evaluates St. John's wort (SJW), another herbal preparation. METHODS: These compounds were evaluated in the forced swimming test in mice, and the corresponding changes in the neurotransmitter levels were measured. RESULTS: Three water-soluble curcumin formulations, C-5, C-20 and C-50 (50-200 mg/kg p.o.) decreased the immobility period, and increased serotonin and dopamine levels in the brain tissues. A subeffective dose (50 mg/kg) of these formulations enhanced the antidepressant-like effect of classical antidepressants with varied mechanisms of action. In addition, an SJW dose of 25 mg/kg showed a significant antidepressant-like effect in all the behavioral studies and also significantly increased brain neurotransmitter levels, especially that of serotonin. The effects produced by C-5 were comparable with those of SJW and fluoxetine, respectively. CONCLUSION: In all these observations, the water-soluble formulations showed a significant antidepressant-like effect, including enhancement of neurotransmitter levels as compared to the similar dose of a conventional curcumin preparation. Thus, these formulations may be used as a novel treatment option in the management of mental depression.

Effect of Convolvulus pluricaulis Choisy and Asparagus racemosus Willd on learning and memory in young and old mice: a comparative evaluation.

A dose dependent enhancement of memory was observed with A. racemosus and C. pluricaulis treatment as compared to control group when tested on second day. A. racemosus and C. pluricaulis at the dose of 200 mg/kg, po showed significantly higher percent retentions, than piracetam. Multiple treatment with A. racemosus and C. pluricaulis for three days also demonstrated significant dose dependent increase in percent retentions as compared to control group. The effect was more prominent with C. pluricaulis as compared with piracetam and A. racemosus. A significantly lower percent retention in aged mice was observed as compared to young mice. Aged mice (18-20 months) showed higher transfer latency (TL) values on first and second day (after 24 h) as compared to young mice, indicating impairment in learning and memory. Pretreatment with A. racemosus and C. pluricaulis for 7 days enhanced memory in aged mice, as significant increase in percent retention was observed. Significantly higher retention was observed with C. pluricaulis (200 mg/kg; po) as compared with piracetam (10 mg/kg/; po). Post-trial administration of C. pluricaulis and A. racemosus extract demonstrated significant decrease in latency time during retention trials. Hippocampal regions associated with the learning and memory functions showed dose dependent increase in AChE activity in CA 1 with A. reacemosus and CA3 area with C. pluracaulis treatment. The underlying mechanism of these actions of A. racemosus and C. pluricaulis may be attributed to their antioxidant, neuroprotective and cholinergic properties.

Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders.

Berberine, an isoquinoline alkaloid of the protoberberine type found in an array of plants, has been used in Indian and Chinese medicines as an antimicrobial, stomachic, bitter tonic and in the treatment of oriental sores. Although pharmacological investigations of berberine have been reported by many in the past, there is renewed interest in berberine because of its reported beneficial effect in various neurodegenerative and neuropsychiatric disorders. The alkaloid is reported to modulate neurotransmitters and their receptor systems in the brain. This review attempts to discuss the pharmacological basis of the use of berberine in various central nervous system and related disorders. Its protective effect in Alzheimer's, cerebral ischemia, mental depression, schizophrenia and anxiety are highlighted. However, more detailed clinical trials along with a safety assessment of berberine are warranted for positioning the alkaloid in the treatment of neurological disorders.

Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice.

The present study was undertaken to compare the anticonvulsant effect of various antiepileptic drugs on the intravenous pentylenetetrazol (PTZ)-induced seizure threshold in mice. Minimal doses of PTZ needed to induce different phases (myoclonic jerks, generalized clonus and tonic extensor) of convulsions were recorded as an index of seizure threshold. Furthermore, TID50 (the dose of an anticonvulsant drug required to increase the PTZ seizure threshold for tonic extensor by 50%) was calculated for all drugs, and from these values the potency ratio was determined. Pentobarbital (10-40 mg/kg i.p.), phenobarbital (5-20 mg/kg i.p.), phenytoin (20-40 mg/kg i.p.), carbamazepine (5-20 mg/kg i.p.), diazepam (0.5-2 mg/kg i.p.), chlordiazepoxide (1-4 mg/kg i.p.), triazolam (0.02-0.08 mg/kg i.p.), clonazepam (0.03125-0.25 mg/kg i.p.), GABA (25-100 mg/kg i.p.), ethanol (1000-4000 mg/kg of 10% v/v p.o.), ashwagandha (50-200 mg/kg p.o.), tiagabine (20 and 40 mg/kg i.p.), gabapentin (50-200 mg/kg i.p.), pregabalin (10-40 mg/kg i.p.), progesterone (20-80 mg/kg s.c.), adenosine (25-200 mg/kg i.p.) and rofecoxib (1-4 mg/kg i.p.) exhibited dose-dependent anticonvulsant effects. The TID50 of triazolam was found to be the lowest among all the drugs tested, indicating higher potency. The relative potency of standard drugs to increase the PTZ seizure threshold for tonic extensor was found to be: triazolam > clonazepam > diazepam > rofecoxib > chlordiazepoxide > phenobarbital > carbamazepine > pentobarbital > pregabalin > phenytoin > progesterone > tiagabine > GABA > adenosine > gabapentin > ashwagandha > ethanol. The results of the present study indicate that the intravenous PTZ seizure threshold may be useful for assessing the anticonvulsant effect of drugs effective against different stages of convulsions.

Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system.

Withania somnifera (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of W. somnifera root extract (Ws) alone or in combination with exogenous gamma-amino butyric acid (GABA), a GABA receptor agonist or with diazepam, a GABA receptor modulator against pentylenetetrazol (PTZ, iv) seizure threshold in mice. Minimal dose of PTZ (iv, mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions were recorded as an index of seizure threshold. Ws (100 or 200 mg/kg, po) increased the PTZ seizure threshold for the onset of tonic extension phase whereas a lower dose (50 mg/kg, po) did not show any effect on the seizure threshold. Co-administration of a sub-effective dose of Ws (50 mg/kg, po) with a sub-protective dose of either GABA (25 mg/kg, ip) or diazepam (0.5 mg/kg, ip) increased the seizure threshold. The results suggested that the anticonvulsant effect of W. somnifera against PTZ seizure threshold paradigm involved the GABAAergic modulation.

Withania somnifera: an Indian ginseng.

Withania somnifera, popularly known as Ashwagandha is widely considered as the Indian ginseng. In Ayurveda, it is classified as a rasayana (rejuvenation) and expected to promote physical and mental health, rejuvenate the body in debilitated conditions and increase longevity. Having wide range of activity, it is used to treat almost all disorders that affect the human health. The present review discusses the pharmacological basis of the use of W. somnifera in various central nervous system (CNS) disorders, particularly its indication in epilepsy, stress and neurodegenerative diseases such as Parkinson's and Alzheimer's disorders, tardive dyskinesia, cerebral ischemia, and even in the management of drug addiction.

Effect of withdrawal of diazepam or morphine treatment on gastric motility (charcoal meal test) in mice: possible role of different central and peripheral receptors.

Increased gastrointestinal motility in mice as one of the withdrawal symptoms of commonly abused drugs like diazepam or morphine and its possible mechanism of action was studied. Male Laka mice (20-25 g) were made addict to either diazepam (20 mg/kg, ip for 7 days) or morphine (10 mg/kg, sc for 9 days). Withdrawal symptoms were noted 24 hr after the last injection of diazepam or morphine. The animals were injected with Ro 15-1788 (flumazenil) (1 mg/kg, ip) or naloxone (2 mg/kg, ip) in the respective group to precipitate the withdrawal symptoms. Gastrointestinal motility was assessed by charcoal-meal test. Animals developed tolerance to acute sedative effect of diazepam, and similarly to the acute nociceptive action of morphine. On abrupt cessation of these drugs after chronic treatment the animals showed hyperlocomotion and hyperreactivity in diazepam withdrawal group and hyperalgesia on hot plate in morphine withdrawal groups, respectively. Increase in gastrointestinal motility was observed in all the drug withdrawal groups. Treatment with respective antagonists, Ro 15-1788 (flumazenil) and naloxone precipitated the withdrawal symptoms. The results suggest the involvement of both central and peripheral receptors of benzodiazepines and opioid (mu) receptors in the withdrawal symptoms of the benzodiazepines and morphine, respectively.

Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice.

The central cholinergic pathways play a prominent role in the learning and memory processes. Acetylcholinesterase is an enzyme that inactivates acetylcholine. The present study was undertaken to estimate the acetylcholinesterase- inhibiting activity of extracts of Glycyrrhiza glabra, Myristica fragrans seeds, and ascorbic acid and compare these values with a standard acetylcholinesterase-inhibiting drug, metrifonate. Aqueous extract of G. glabra (150 mg/kg p.o. for 7 successive days), n-hexane extract of M. fragrans seeds (5 mg/kg p.o. for 3 successive days), ascorbic acid (60 mg/kg i.p. for 3 successive days), and metrifonate (50 mg/kg i.p.) were administered to young male Swiss albino mice. Acetylcholinesterase enzyme was estimated in brains of mice. G. glabra, M. fragrans, ascorbic acid, and metrifonate significantly decreased acetylcholinesterase activity as compared with their respective vehicle-treated control groups.

Resveratrol, a polyphenolic phytoalexin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats.

The effects of resveratrol, a polyphenolic phytoalexin present in red wine have been investigated on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65mg/kg). After 4-weeks of STZ injection, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with controls rats. Chronic treatment with resveratrol (10mg/kg orally) from week 4 to week 6 significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of oxidative stress in development of hyperalgesia and cold allodynia in diabetic animals and point towards the potential of resveratrol as an adjuvant therapy for the prevention and treatment of diabetic neuropathy.

Protective effect of BR-16A, a polyherbal preparation against social isolation stress: possible GABAergic mechanism.

The antistress effects of BR-16A, a polyherbal preparation and its interaction with GABAergic modulators against social isolation-induced stress were investigated in the present study. Isolation stress was induced by keeping the mice (Laca strain) individually in each cage for 3 weeks and various drug treatments were given for a period of 5 days before the start of the experiments. The various behavioural parameters examined included pentobarbitone-induced sleep (sleep latency and duration), analgesia (tail-ssick test) and locomotor activity, respectively. BR-16A (100 mg/kg and 200 mg/kg) treatment for 5 days significantly reversed the social isolation stress-induced prolongation of onset and decrease in pentobarbitone-induced sleep, increased total motor activity and stress-induced antinociception. When diazepam (0.5 mg/kg), a benzodiazepine agonist, was co-administered with BR-16A (100 mg/kg), it significantly potentiated the reversal of pentobarbitone-induced shortening of sleep time effects; increased locomotor activity and stress induced antinociceptive effects. However, the sleep latency was not decreased significantly. Further, ssumazenil (2 mg/kg), a benzodiazepine receptor antagonist and FG 7142 (10 mg/kg), an inverse agonist, when co-administered with BR-16A (100 mg/kg), showed no significant reversal on pentobarbitone-induced hypnosis, locomotor activity and social isolation-induced antinociception compared with their effects per se. The present study demonstrated the antistress effects of BR-16A preparation against social isolation-induced stress. The present study also suggests that the GABAergic system may be involved in its antistress effect.

Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in mice.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons, however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs for Parkinsonism. Administration of haloperidol (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced catalepsy. The results indicate that BR-16A or ashwagandha has protective effect against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A could be used in preventing the drug-induced extrapyramidal side effects and may offer a new therapeutic approach to the treatment of Parkinson's disease.

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.

Protective effect of quercetin on alcohol abstinence-induced anxiety and convulsions.

Chronic administration of ethanol (2 g/kg, p.o.) on days 1-6 and its withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored-chamber test. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced anxiety in mice. However, acute administration of a single dose of quercetin (50 mg/kg) to animals withdrawn from ethanol, i.e., on day 7, did not prevent withdrawal-induced anxiety. Ethanol withdrawal also induced a significant increase in the locomotor activity of mice indicating an anxiogenic response. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced increased locomotor activity. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40-60 mg/kg) of PTZ produced full-blown convulsions and increased mortality in ethanol-withdrawn mice. Both acute and chronic administration of quercetin (25 or 50 mg/kg, p.o.) produced a significant protection against ethanol withdrawal-induced reduction in PTZ threshold in mice. The result suggests the protective effect of this safe drug, quercetin, in the management of ethanol withdrawal reactions.

Improvement of mouse memory by Myristica fragrans seeds.

Memory is one of the most complex functions of the brain and involves multiple neural pathways and neurotransmitter systems. The present study was undertaken to investigate the effect of Myristica fragrans (MF) seeds on learning and memory in mice. The n-hexane extract of MF was administered orally in three doses (5, 10, and 20 mg/kg p.o.) for 3 successive days to different groups of young and aged mice. The learning and memory parameters were assessed using elevated plus-maze and passive-avoidance apparatus. The effect of MF extract on scopolamine (0.4 mg/kg i.p.)- and diazepam (1 mg/kg i.p.)-induced impairment in learning and memory was also studied. MF extract at the lowest dose of 5 mg/kg p.o. administered for 3 successive days significantly improved learning and memory of young and aged mice. This extract also reversed scopolamine- and diazepam-induced impairment in learning and memory of young mice. MF extract enhanced learning and retention capacities of both young and aged mice. The exact mechanism of the memory-improving effect of MF extract was not explored in the present study. But, the observed memory-enhancing effect may be attributed to a variety of properties (individually or in combination) the plant is reported to possess, such as antioxidant, anti-inflammatory, or perhaps procholinergic activity.

On the sleep promoting effects of BR-16A: interaction with GABAergic modulators.

Pentobarbitone-induced hypnosis test was used as an animal model to explore the role of BR-16A, a polyherbal formulation in sleep. Pentobarbitone produces quick sleep latency (onset) and prolongation of total sleep time (duration). Sleep latency and total sleep time were used as a parameters for the evaluation. BR-16A potentiated the effect of triazolam (0.1 mg/kg, ip) and alprazolam (0.25 mg/kg, ip). Melatonin (5.0 mg/kg, ip) and zolpidem (0.5 mg/kg, ip) did not produce any significant effect on sleep parameters. However, alprazolam (0.25mg/kg, ip) potentiated the effect of BR-16A (100 mg/ kg, po) in higher dose only. Sleep promoting effect of BR-16A in combination with GABAergic drugs (triazolam and alprazolam,) suggested that these drugs have common mechanism in sleep promoting effect of pentobarbitone and could be used along with other GABAergic hypnotics for the treatment of insomnia. This may reduce the dose of the latter drug(s). BR-16A can be used for the treatment of sleep and sleep-related disorders.

Memory enhancing activity of Glycyrrhiza glabra in mice.

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra (family: Leguminosae) have been employed clinically for centuries for their anti-inflammatory, antiulcer, expectorant, antimicrobial and anxiolytic activities. The present study was undertaken to investigate the effects of Glycyrrhiza glabra (popularly known as liquorice) on learning and memory in mice. Elevated plus-maze and passive avoidance paradigm were employed to test learning and memory. Three doses (75, 150 and 300 mg/kg p.o.) of aqueous extract of Glycyrrhiza glabra were administered for 7 successive days in separate groups of animals. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose significantly reversed the amnesia induced by diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory was due to facilitation of cholinergic-transmission in mouse brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, Glycyrrhiza glabra has shown promise as a memory enhancing agent in all the laboratory models employed.

Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models.

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra have been employed clinically for centuries for their anti-inflammatory, anti-ulcer, expectorant, antimicrobial, and anxiolytic activities. The present study was undertaken to investigate the effects of G. glabra, popularly known as liquorice (Mulathi), on learning and memory. The elevated plus-maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (75, 150, and 300 mg/kg p.o.) of aqueous extract of G. glabra were administered for 7 successive days in separate groups of mice. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose reversed the amnesia induced by diazepam (1 mg/kg i.p.), scopolamine (0.4 mg/kg i.p.), and ethanol (1 g/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory may be because of facilitation of cholinergic transmission in brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, G. glabra has shown promise as a memory enhancer in both exteroceptive and interoceptive behavioral models of memory.

Involvement of normal physiological mechanisms in mediation of satiety by polyherbal antiobesity preparation, OB-200G, in female mice.

The first study investigated the effect of different doses (0.25, 0.5, 1 g/kg p.o.) of a polyherbal, antiobesity preparation, OB-200G, on the duration of a specific sequence of behaviors (activity, feeding, grooming and resting) associated with the onset of satiety. The recordings were taken at 0, 30 and 60 min, for 10-min periods, immediately after the presentation of sweetened chow to female mice that had been fasted for 16 h. At the end of a 70-min test session, the amount of sweetened chow consumed by each mouse was also recorded. The second study investigated the antagonism of hyperphagia mediated by 2-deoxy-D-glucose (2-DODG), by both OB-200G (0.5 g/kg) and fluoxetine (10 mg/kg). Ingestion of sweetened chow by control mice produced the typical sequence of behaviors associated with the onset of satiety, characterized by initial increase in duration of feeding and active behaviors. With time, these behaviors declined and there was an increase in grooming and resting behaviors. Prefeeding significantly (p < 0.01) decreased the percentage of time spent feeding but also significantly (p < 0.01) increased the duration of active behaviors at 0-10 and 30-40 min. Prefeeding for 20 min advanced the onset and increased the duration of grooming behavior. Treatment with fluoxetine (10 mg/kg) significantly decreased the duration of feeding behavior and increased the active behavior duration at 0-10 and 30-40 min as compared with the control group. There was also a significant (p < 0.01) increase in resting behavior duration with fluoxetine at 60-70 min. OB-200G (0.25-1 g/kg) administration significantly decreased the feeding behavior duration and increased the active-behavior duration at 30-40 min as compared with the control group during that period. However, OB-200G (0.25-I g/kg) did not elicit any significant change in grooming (except decrease at 60-70 min with a 0.5 g/kg dose) and resting behavior duration compared with the control or prefed groups. The amount of sweetened chow consumed significantly decreased (p < 0.01) in 10 and 20 min prefed, fluoxetine-treated and OB-200G-treated (0.5 and 1 g/kg) mice as compared with the control group. Furthermore, the hyperphagia mediated by 2-DODG was significantly antagonized by both OB-200G and fluoxetine. In conclusion, like fluoxetine, OB-200G mediates satiety through operation of normal physiological mechanisms. Antagonism of 2-DODG-hyperphagia by OB-200G and fluoxetine indicates the involvement of a common central pathway (or pathways) in their action.

Investigations on possible serotonergic involvement in effects of OB-200G (polyherbal preparation) on food intake in female mice.

BACKGROUND: OB-200G is a polyherbal preparation containing aqueous extracts of Garcinia cambogia, Gymnema sylvestre, Zingiber officinale, Piper longum and resin from Commiphora mukul, all possessing thermogenic properties. Our previous studies reveal OB-200G to exert antiobesity effects in dietary animal models of obesity. AIM OF THE STUDY: The present study investigated the possible involvement of serotonergic system in the effect of OB-200G on food intake. We examined the effects of systemic pretreatment with 5-HT depletor, p-chlorophenylalanine (PCPA, 300 mg/kg, i. p. for 6 days), 5-HT1A agonist, (8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.1 mg/kg, i. p.), nonselective 5-HT antagonist, cyproheptadine (1 mg/kg, i. p.), 5-HT2 receptor antagonist, seganserin (1 and 2 mg/kg, i. p.) and 2-deoxy-D-glucose (2-DG, glucose antimetabolite, 500 mg/kg, i. p.) on satiety induced by OB-200G (500 mg/kg, p. o.) in non-deprived female mice. The results were compared with fluoxetine (10 mg/kg, i. p.), a selective serotonin reuptake inhibitor. METHODS: Fifteen minutes after the last drug administration, groups of mice were presented with sweetened chow and the amount of food consumed was recorded at 0.5,1,2, 3 and 4h time intervals. RESULTS: The hyperphagic effect of PCPA, 8-OH-DPAT, cyproheptadine and 2-DG was significantly (p < 0.05) antagonized by both OB-200G and fluoxetine. However, the anorectic effect of fluoxetine was not reversed by centrally acting 5-HT2 antagonist, seganserin but the latter markedly attenuated the satiety action of OB-200G. CONCLUSION: The present observations suggest the role of serotonin in mediation of satiety by OB-200G and hence its antiobesity effect.