Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats.

BACKGROUND: Berberine is a natural plant alkaloid and has been reported to possess anti-inflammatory activity. However, berberine's poor bioavailability and low solubility have limited its clinical applicability. Nanoencapsulation of berberine using a suitable carrier can be a promising strategy to improve its efficacy. Therefore, this study aimed to produce berberine-loaded gum nanocomplexes to evaluate their therapeutic effects in a carrageenan-induced rat model. METHODS: Berberine-loaded gum nanocomplexes were prepared by the ionic complexation between the negative charges of the gums (tragacanth and acacia gum) using a cross-linker for loading cationic berberine and their anti-inflammatory activity was evaluated against carrageenan-induced paw edema in rats. ELISA and qRT-PCR were employed to measure the concentration and mRNA expression level of inflammatory mediators in plasma and paw tissue, respectively. RESULTS: Berberine nanocomplexes were characterized for particle size (219.5 nm), zeta potential by the dynamic light scattering (DLS), and for entrapment efficiency (93.2%) Infrared spectroscopy affirmed the loading of berberine in gum nanocomplexes. Transmission electron microscopy of formulation showed the spherical shape of nanocomplexes and small particle size (100-150 nm). Pretreatment of rats with berberine nanocomplexes significantly reduced the paw edema in inflamed rat paws, decreased the production of nitrite and TNF-α in plasma and repressed the mRNA expression levels of TNF-α and IL-1ß in paw tissue in comparison to berberine per se treated rats. CONCLUSION: The obtained berberine-loaded gum nanocomplexes produced a better anti-inflammatory effect as compared to berberine alone and hence can be used as an efficient candidate in the treatment of inflammation. The schematic representation of the preparation of the preparation of berberine-loaded tragacanth/acacia gum nanocomplexes and the evaluation in vivo for anti-inflammatory effects.

Antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima in unstressed and stressed mice

In the present study, antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima was evaluated in Swiss young male albino mice. Stress was induced in mice by subjecting them to unpredictable mild stress for 21 successive days. Ethanol extract of the leaves (100, 200 and 400 mg/ kg, p.o.) and fluoxetine (20 mg/kg, p.o.) were administered for 21 consecutive days to separate groups of unstressed and stressed mice. Ethanol extract (200 and 400 mg/kg) and fluoxetine significantly decreased immobility period of unstressed as well as stressed mice in tail suspension test (TST). However, the lowest dose (100 mg/kg) of the extract also significantly decreased immobility period of stressed mice in TST. The extract significantly restored reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice. Ethanol extract of the leaves significantly decreased plasma nitrite and corticosterone levels; brain MAO-A activity and MDA level; and increased brain reduced glutathione and catalase activity in unstressed as well as stressed mice as compared to their respective vehicle treated controls. Thus, ethanol extract of leaves of Caesalpinia pulcherrima showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-Aactivity, reduction of oxidative stress and plasma corticosterone levels.

Antidiabetic activity enhancement in streptozotocin + nicotinamide-induced diabetic rats through combinational polymeric nanoformulation.

Background: The bioactive compounds glycyrrhizin (GL) and thymoquinone (TQ) have been reported for antidiabetic activity in pure and nanoformulation (NF) form. However, the antidiabetic effect of a combined nanoformulation of these two has not been reported in the literature. Here, a combinational nanomedicine approach was investigated to enhance the antidiabetic effects of the two bioactive compounds of GL and TQ (GT), in type 2 diabetic rats in reference to metformin. Methods: Two separately prepared NFs of GL (using polymeric nanoparticles) and TQ (using polymeric nanocapsules) were mixed to obtain a therapeutic cargo of nanomedicine and then characterized with respect to particle size, stability, morphology, chemical interaction, and in vivo behavior. Additionally, NFs were evaluated for their cytotoxic effect on Vero cell lines compared to the pure form. This nanomedicine was administered orally, both independently and in combination (pure form or NF) for 21 successive days to type 2 diabetic rats and the effect assessed in term of body weight, fasting blood-glucose level, and various biochemical parameters (such as lipid-profile parameters and HbA1c). Results: When these nanomedicines were applied in combined rather than individual forms, significant decreases in blood glucose and HbA1c and significant improvements in body weight and lipid profile were observed, despite them containing lower amounts than the pure forms. The treatment of diabetic rats with GL and TQ, when administered independently in either pure or NF forms, did not lead to favorable trends in any studied parameters. Conclusion: The administration of combined GT NFs exhibited significant improvement in studied parameters. Improvements in antidiabetic activity could have been due to a synergistic effect of combined NFs, leading to enhanced absorption of NFs and lesser cytotoxic effects compared to pure bioactive compounds. Therefore, GT NFs demonstrated potential as a new medicinal agent for the management of diabetes.

Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats.

In the present study, the effect of inosine was evaluated on learning and memory of 18 months old aged female rats. Inosine (50, 100 and 200 mg/kg; i.p.) was administered to separate groups of rats for 15 successive days. Donepezil (1 mg/kg; i.p.), an acetylcholinesterase inhibitor, was used as a standard drug. Behavioral models such as Morris water maze and elevated plus maze were used to evaluate the effect of drugs on learning and memory of rats. After behavioral studies, animals were killed and their brain was isolated and further processed for estimation of various biochemical parameters such as acetylcholinesterase activity, oxidative stress markers, proinflammatory marker and histological examinations. Inosine (100 and 200 mg/kg) significantly improved learning and memory of aged rats. Further, inosine significantly reduced lipid peroxidation and nitrite, and increased the levels of reduced glutathione and superoxide dismutase. However, no significant difference in AChEs activity was observed in inosine-treated rats as compared to aged control rats. TNF-α level was found to be ameliorated in aged rats by inosine. Histopathological evaluation showed that inosine-treated aged rats have less number of pyknotic neurons in hippocampal CA1 region as compared to aged control rats. In conclusion, inosine significantly improved learning and memory of aged female rats possibly through its antioxidant as well as anti-inflammatory effect and improvement of neuronal survival in the hippocampal CA1 region. However, additional studies are required to further explore the downstream signaling pathways involved in the neuroprotective effect of inosine in aged animals.

Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes.

Thymoquinone is a bioactive constituent of Nigella sativa seeds. It has been reported to possess antihyperglycemic effect in rats. However, the effect of nanoformulation (NF) of thymoquinone has not been reported in literature. So, the present study was designed with the aim to investigate the effect of nanoformulation of thymoquinone in streptozotocin-nicotinamide induced type-2 diabetic rats and compare its effect with pure bioactive compound as well as metformin, a standard antidiabetic drug. It is the first study reporting the use of thymoquinone NF against diabetes. Polymeric nanocapsules (NCs) of thymoquinone and metformin were prepared by nanoprecipitation method using gum rosin, a biocompatible polymer. Box-Behnken statistical analysis tool was used for the optimization of polymer and other excipients. The NCs were then characterized with respect to particle size, stability, morphology, and in vitro drug dissolution profiles. Furthermore, thymoquinone (20, 40 & 80 mg/kg), metformin (150 mg/kg) and their nanoformulations (20, 40 & 80 mg/kg for thymoquinone and 80 mg/kg for metformin) per se were administered for 21 successive days to type-2 diabetic rats. Body weight and blood glucose levels were measured every week for 3 weeks. Serum lipid profile and glycosylated hemoglobin were estimated on 22nd day. The nanocapsules were stable, spherical in shape and size was less than 100 nm. Thymoquinone-and metformin-loaded NCs showed sustained release profile as compared to their pure forms. Oral administration of thymoquinone, metformin and their nanoformulations significantly decreased blood glucose level and glycated haemoglobin; and improved the lipid profile of diabetic rats as compared to diabetic control rats. Thymoquinone-loaded NCs (containing 10, 20 and 40 mg of thymoquinone) produced dose-dependent antihyperglycemic effect and this effect was comparable to thymoquinone and metformin. In conclusion, thymoquinone nanocapsules (actually containing half of the doses of thymoquinone) produced better antihyperglycemic effect in type-2 diabetic rats as compared to thymoquinone alone.

Protective effect of hesperetin against haloperidol-induced orofacial dyskinesia and catalepsy in rats.

OBJECTIVES: The present study was designed to evaluate the effect of hesperetin on haloperidol-induced orofacial dyskinesia and catalepsy in Wistar male albino rats. METHODS: Haloperidol (1 mg/kg, ip) was administered for 21 successive days to induce orofacial dyskinesia and catalepsy. Hesperetin (50 and 100 mg/kg, po) was administered 10 min prior to the injection of haloperidol for 21 successive days. Vacuous chewing movements (VCMs), tongue protrusions, catalepsy, and locomotor activity scores were recorded on 7th, 14th, and 22nd day of drug treatment. After behavioral testing, animals were sacrificed and various biochemical parameters such as brain levels of dopamine, serotonin, malondialdehyde, and reduced glutathione (GSH); and superoxide dismutase (SOD) and catalase activities were estimated. RESULTS: Chronic administration of haloperidol significantly increased VCMs, tongue protrusions, and catalepsy in rats. It also produced hypolocomotion in rats. Hesperetin significantly inhibited haloperidol-induced VCMs, tongue protrusions, and catalepsy. Haloperidol significantly increased brain levels of malondialdehyde, decreased brain GSH, SOD, and catalase activities; and also decreased brain dopamine and serotonin levels. Hesperetin significantly reversed haloperidol-induced increase in brain oxidative stress and decrease in brain dopamine and serotonin levels. DISCUSSION: Hesperetin significantly ameliorated haloperidol-induced orofacial dyskinesia and catalepsy possibly through alleviation of oxidative stress and increase in brain dopamine and serotonin levels. Thus, hesperetin may be explored further as a possible therapeutic agent for clinical management of neuroleptic drug-induced tardive dyskinesia.

Behavioral and biochemical evidences for nootropic activity of boldine in young and aged mice.

Boldine, a bioactive compound, has been reported to be neuroprotective, but its effect on learning and memory has not been explored. So, the present study was aimed to study the effect of boldine on the learning and memory of the Swiss albino male young and aged mice. Boldine (1.5, 3 and 6mg/kg, po) and physostigmine salicylate (0.1mg/kg, ip) were administered to separate groups of mice for 7 successive days. Morris water maze was utilized as a behavioural model to study the effect of drugs on learning and memory of mice. Boldine and physostigmine significantly improved learning and memory of young as well as aged mice, as indicated by decrease in escape latency time during training session and increase in time spent in target quadrant during retrieval session. No significant effect on locomotor activities of mice was observed due to drug treatments. Memory-enhancing activity of boldine (3mg/kg) was found to be comparable to physostigmine. Boldine significantly reversed scopolamine-, sodium nitrite- and aging-induced amnesia in mice. Moreover, boldine attenuated oxidative stress, as shown by a significant decrease in brain malondialdehyde as well as brain nitrite levels and a significant increase in brain GSH level of young as well as aged mice. Brain acetylcholinesterase activity was also significantly inhibited by boldine in young as well as aged mice. In conclusion boldine administered for 7 successive days exhibited significant improvement of learning and memory of young and aged mice possibly through inhibition of brain acetylcholinesterase activity and alleviation of brain oxidative stress.

Evaluation of anti-diabetic activity of glycyrrhizin-loaded nanoparticles in nicotinamide-streptozotocin-induced diabetic rats.

Glycyrrhizin is an active constituent of the roots and rhizomes of Glycyrrhiza glabra and has anti-hyperglycemic effects. In this study, nanoparticles (NPs) loaded with glycyrrhizin or metformin were evaluated in vivo for their anti-hyperglycemic potency towards type-II diabetes in rats. The NPs were produced via the ionotropic gelation method using the biocompatible polymers chitosan and gum arabic. The polymer concentration was optimized using the 32 factorial method to acquire both minimum particle size and maximum encapsulation efficiency. The NPs were then characterized with respect to particle size, encapsulation efficiency, stability, chemical interactions, and in vitro drug dissolution profiles using spectroscopic and microscopic analysis. Furthermore, glycyrrhizin and metformin and their nanoformulations were administered for 21 successive days to diabetic rats. Glycyrrhizin-loaded NPs had significant anti-diabetic effects even though they contained approximately one quarter of the dosage relative to the pure form.

Metformin-loaded alginate nanoparticles as an effective antidiabetic agent for controlled drug release.

OBJECTIVES: Present modalities for the diagnosis and treatment of diabetes still suffer from certain limitations such as erratic absorption, need of high dose, poor sensitivity or specificity, resistance, substantial morbidity and mortality, long-term complications, and patient-to-patient variability with lifetime treatment. METHODS: This study focused on the development of a water-in-oil-in-water metformin nanoemulsion as an effective method in diabetes treatment. As a Biopharmaceutics Classification System (BCS) class III drug, metformin is hydrophilic in nature with high solubility and poor absorption characteristics. To simultaneously facilitate gastrointestinal absorption and intestinal permeability, metformin was loaded into alginate nanocapsules prepared by an emulsion cross-linking technology. KEY FINDINGS: These prepared metformin-loaded alginate nanoparticles (MLANs) were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and photon correlation spectroscopy (PCS)-based particle size analysis. CONCLUSIONS: The drug loading and encapsulation efficiency in MLANs were 3.12 mg (the amount of metformin added in 100 mg of nanoparticles) and 78%, respectively. The results of in-vitro drug release studies and in-vivo efficacy tests (using animal models) demonstrated enhanced efficiency and response of MLANs relative to pure metformin. The efficacy of MLANs (46.8 mg/kg) was overall about three times higher than that of pure metformin150 mg/kg.

Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice.

INTRODUCTION: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action. METHODS: The seed oil (50, 100, and 200 mg/kg, PO) and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14(th) day, 60 min after drug administration, animals were subjected to Tail Suspension Test (TST) and Forced Swim Test (FST). The mechanism of action was also studied. RESULTS: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine (P<0.0001). ED50 value of celastrus seed oil using FST and TST were 17.38 and 31.62 mg/kg, respectively. The oil did not show any significant effect on locomotor activity. It significantly inhibited brain MAO-A activity and decreased plasma corticosterone levels. Sulpiride (selective D2-receptor antagonist), p-CPA (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST. DISCUSSION: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO-A activity and decrease in plasma corticosterone levels.

Antidepressant-like activity of plumbagin in unstressed and stressed mice.

BACKGROUND: Plumbagin has been reported to be neuroprotective, so it might possess antidepressant activity. Therefore, the present study was designed to explore the antidepressant potential of plumbagin in unstressed and stressed mice. METHODS: Depression-like behavior was induced in Swiss male albino mice by subjecting them to unpredictable mild stress daily for 21 successive days. Plumbagin (4, 8 and 16mg/kg, po) and imipramine (15mg/kg, po) were administered for 3 successive weeks to separate groups of unstressed and stressed mice. Tail suspension test and sucrose preference test were used to evaluate antidepressant effect of the drugs. RESULTS: Highest dose (16mg/kg) of plumbagin and imipramine significantly decreased immobility period of unstressed and stressed mice in tail suspension test as compared to their respective controls. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. The drugs did not significantly affect locomotor activity of mice. Antidepressant-like activity of plumbagin was found to be comparable to imipramine. Plumbagin and imipramine significantly inhibited brain MAO-A activity, decreased plasma nitrite, brain malondialdehyde and catalase levels; and increased reduced glutathione levels of unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. CONCLUSIONS: Antidepressant-like activity of plumbagin in unstressed and stressed mice might be through inhibition of brain MAO-A activity and improvement of antioxidant status. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of plumbagin in stressed mice.

Optimization and evaluation of bioactive drug-loaded polymeric nanoparticles for drug delivery.

The premise of the present study was to suitably select or modify the constitution of the polymer matrix to achieve significantly high entrapment of hydrophilic drugs within polymeric nanoparticles (NPs). Glycyrrhizin (GL), the bioactive drug was selected as a representative hydrophilic drug. Ionotropic gelation technique was used for the preparation of glycyrrhizin-loaded NPs. Concentration of polymers were optimized by 3-level factorial design which affected the particle size and encapsulation efficiency. The formulation was subjected to morphological, physiochemical and in vitro drug release studies. Mean particle size of nanoparticles was around 181 nm as estimated with particle size analyzer. TEM observations revealed spherical shape and size in the range of 140-200 nm. Fourier transform-infrared analysis did not reveal any chemical interaction among the drug and polymers used for the nano-formulation. A release study conducted in vitro over a period of 24 h indicated primarily burst release after that controlled release of glycyrrhizin from the formulation. Antibacterial activities of glycyrrhizin, blank chitosan-gum arabic NPs and glycyrrhizin-loaded chitosan-gum arabic NPs were tested against two Gram negative and two Gram positive bacteria. The study demonstrates the benefit of excipient screening techniques in improving entrapment efficiency of a hydrophilic drug.

Punarnavine, an alkaloid isolated from ethanolic extract of Boerhaavia diffusa Linn. reverses depression-like behaviour in mice subjected to chronic unpredictable mild stress.

Punarnavine (20 and 40 mg/kg) and fluoxetine (20 mg/kg) per se administered orally for 14 successive days significantly decreased immobility periods of both unstressed and stressed mice in forced swim test. These drugs also significantly decreased sucrose preference in both stressed and unstressed mice as compared to their respective controls, indicating significant antidepressant-like activity. The drugs did not show any significant effect on locomotor activity of mice. The alkaloid also significantly decreased monoamine oxidase (MAO-A) activity, malondialdehyde levels in both unstressed and stressed mice; and significantly reversed the stress-induced decrease in reduced glutathione and catalase activity. It also significantly attenuated the stress-induced increase in plasma nitrite and corticosterone levels. Thus, punarnavine showed antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, punarnavine also showed antidepressant-like activity in stressed mice possibly through decrease in plasma corticosterone levels.

Possible involvement of GABAergic and nitriergic systems for antianxiety-like activity of piperine in unstressed and stressed mice.

BACKGROUND: An investigation was made to explore the possibility of anxiolytic activity of piperine in unstressed and stressed mice along with the underlying role of nitriergic and GABAergic modulation for the noted activity of piperine. METHODS: Piperine (5, 10 and 20mg/kg, ip) was administered to unstressed mice. In another groups of animals, piperine was administered 30 min before subjecting them to immobilization stress for 6h. Antianxiety activity was evaluated by employing elevated plus maze, light-dark box and social interaction test. Diazepam was employed as standard anxiolytic drug. RESULTS: Piperine produced significant antianxiety-like activity in unstressed and stressed mice. The anxiolytic-like activity of piperine was comparable to diazepam. In unstressed mice, piperine significantly increased brain GABA levels, but could not produce any change in plasma nitrite levels. Meanwhile, in stressed mice, piperine did not produce any significant change in GABA levels, but significantly decreased nitrite levels. Pre-treatment with aminoguanidine (50mg/kg, ip), an inducible nitric oxide synthase (NOS) inhibitor, significantly potentiated the anxiolytic-like activity of piperine, as compared to piperine and aminoguanidine alone in stressed mice. On the other hand, pretreatment with 7-nitroindazole (20mg/kg, ip), a neuronal NOS inhibitor significantly potentiated the antianxiety-like activity of piperine, as compared to piperine and 7-nitroindazole alone in unstressed mice. CONCLUSION: These data suggest that the piperine produced significant anxiolytic activity in unstressed mice possibly through increase in GABA levels and inhibition of neuronal NOS. On the other hand, antianxiety activity in stressed mice might be through inhibition of inducible NOS.

Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress.

BACKGROUND: In the present study, antidepressant-like activity of palmatine was evaluated in unstressed and stressed young male Swiss albino mice. METHODS: The animals were subjected to unpredictable mild stress daily for 21 successive days to induce depression-like behavior. Palmatine (0.25, 0.5, 1 mg/kg, ip) was administered for 21 successive days to unstressed and stressed mice. The antidepressant-like activity was evaluated using the tail suspension test, forced swim test and sucrose preference test. RESULTS: Palmatine (0.5 and 1 mg/kg, ip) significantly decreased immobility periods of unstressed and stressed mice in the forced swim test and tail suspension test, thus indicating its significant antidepressant-like activity. Only the highest dose (1 mg/kg) of palmatine significantly reversed the stress-induced decrease in sucrose preference. There was no significant effect on locomotor activity of the mice by palmatine and fluoxetine. The antidepressant-like activity of palmatine was found to be comparable to fluoxetine (10 mg/kg) administered for successive 21 days. Palmatine (0.5 and 1 mg/kg, ip) significantly reversed the stress-induced increase in brain catalase levels, MAO-A activity, lipid peroxidation, plasma nitrite and corticosterone levels. CONCLUSIONS: Palmatine showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of MAO-A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, palmatine also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

Antihyperlipidemic Activity of Aloe succotrina in Rats: Possibly Mediated by Inhibition of HMG-CoA Reductase.

The present study was designed to investigate antihyperlipidemic activity of dried pulp of Aloe succotrina leaves in Wistar albino rats. Hyperlipidemia was induced in rats by feeding them high fat diet (HFD) or D-fructose (25% w/v) for 4 successive weeks. From 15th to 28th day, dried pulp (100 and 200 mg/kg, p.o) and atorvastatin (10 mg/kg, p.o.) per se were administered 2 h prior to feeding rats with HFD or fructose. Aloe succotrina did not significantly decrease the body weight of rats. The dried pulp and atorvastatin per se significantly decreased relative liver weight but did not significantly affect relative heart weight. HFD or fructose significantly increased serum total cholesterol, triglycerides, LDL-c, and VLDL, and decreased HDL-c; significantly increased liver MDA and decreased GSH levels. The dried pulp (200 mg/kg p.o.) significantly reversed high fat diet-induced and fructose-induced hyperlipidemia and atherogenic index. Aloe succotrina significantly decreased HMG Co-A reductase activity. Antihyperlipidemic effect of the dried pulp was comparable to atorvastatin. Thus, Aloe succotrina produced significant antihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats, possibly through normalization of serum lipid profile, HMG-CoA reductase inhibitory activity, and amelioration of oxidative stress in liver.

Behavioural and neuroendocrine effects of aqueous extract of Boerhaavia diffusa Linn. in mice using tail suspension and forced swim tests--a preliminary study.

The present study was done to evaluate the effect of aqueous extract of B. diffusa on depression in mice using behavioral models such as tail suspension test (TST) and forced swim test (FST). The extract (50, 100 and 200 mg/kg, po) was administered for 14 successive days to Swiss young albino mice. On 14th day, 60 min after administration, mice were subjected to TST and FST. The administration of aqueous extract of B. diffusa (50, 100 and 200 mg/kg, po) significantly decreased immobility period in both TST and FST, indicating significant antidepressant-like activity. The lowest dose (50 mg/kg) of the extract decreased the immobility period most significantly in FST, showing most potent antidepressant-like action. The efficacy of the extract (50 mg/kg) was comparable to fluoxetine (20 mg/kg). The extract did not show any significant effect on locomotor activity. The extract showed significant monoamine oxidase -A inhibitory activity. There was no significant effect of the extract on plasma corticosterone levels. Prazosin (alpha1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABA(B) agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect, when tested in TST. The extract might produce antidepressant-like effect by interaction with alpha1-adrenoceptors, dopamine-D2 receptors, serotonergic, and GABA(B) receptors. Thus, aqueous extract of B. diffusa showed significant antidepressant-like activity in mice probably through involvement of monoaminergic and GABAergic systems.

Evidence for involvement of the monoaminergic system in antidepressant-like activity of an ethanol extract of Boerhaavia diffusa and its isolated constituent, punarnavine, in mice.

CONTEXT: Boerhaavia diffusa Linn. (Nyctaginaceae) roots possess potent antioxidant, antistress, and anticonvulsant activities. It is used as a medicinal plant in Ayurvedic and natural herbal medicines. OBJECTIVE: To evaluate the effect of Boerhaavia diffusa root ethanol extract and its active constituent, punarnavine, on depression in Swiss albino mice. MATERIALS AND METHODS: Ethanol extract (50, 100, and 200 mg/kg, p.o.) and punarnavine (20 and 40 mg/kg, p.o.) were separately administered to 22 and 17 groups of mice, respectively, for 14 successive days followed by testing in the tail suspension and forced swim tests (FST). About 2% w/v gum acacia and double distilled water were used as controls for the extract and punarnavine, respectively. RESULTS: Antidepressant-like effect of the lowest dose (50 mg/kg) of the extract and lower dose (20 mg/kg) of punarnavine were found to be comparable to fluoxetine. The ED50 value of the ethanol extract was 26.30 mg/kg (FST) and 33.11 mg/kg (tail suspension test); and of punarnavine was 15.14 mg/kg (FST) and 17.38 mg/kg (tail suspension test). The drugs did not show any significant effect on locomotor activities of mice. Prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), para-chlorophenylalanine) (p-CPA) (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the extract and punarnavine induced-antidepressant-like effect in the tail suspension test. The extract and punarnavine also significantly reduced mouse brain monoamine oxidase (MAO)-A levels, but there was no significant effect on plasma corticosterone levels. CONCLUSION: Ethanol extract of Boerhaavia diffusa and punarnavine produced an antidepressant-like effect in mice probably through interaction with monoaminergic and GABAergic systems.

Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress.

This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

Memory-enhancing activity of palmatine in mice using elevated plus maze and morris water maze.

The present study was designed to evaluate the effect of palmatine on memory of Swiss young male albino mice. Palmatine (0.1, 0.5, 1 mg/kg, i.p.) and physostigmine (0.1 mg/kg, i.p.) per se were administered for 10 successive days to separate groups of mice. Effect of drugs on learning and memory of mice was evaluated using elevated plus maze and Morris water maze. Brain acetylcholinesterase activity was also estimated. Effect of palmatine on scopolamine- and diazepam-induced amnesia was also investigated. Palmatine (0.5 and 1 mg/kg) and physostigmine significantly improved learning and memory of mice, as indicated by decrease in transfer latency using elevated plus maze, and decrease in escape latency during training and increase in time spent in target quadrant during retrieval using Morris water maze. The drugs did not show any significant effect on locomotor activity of the mice. Memory-enhancing activity of palmatine (1 mg/kg) was comparable to physostigmine. Palmatine (1 mg/kg) significantly reversed scopolamine- and diazepam-induced amnesia in mice. Palmatine and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. Thus, palmatine showed memory-enhancing activity in mice probably by inhibiting brain acetylcholinesterase activity, through involvement of GABA-benzodiazepine pathway, and due to its antioxidant activity.