A network pharmacology approach to explore pharmacological mechanisms of Asparagus racemosus for ameliorative effect in epilepsy and comorbid progressive memory dysfunction.

Background: Network pharmacology approach has been observed a powerful tool to predict underlying complex pharmacological mechanism of herbs. Asparagus racemosus has been reported to show ameliorative effects in treating epilepsy and comorbid memory dysfunction but mechanism of this amelioration is elusive. Hence a network pharmacology approach was employed to investigate the plausible mechanism of A. recemosus. Methodology: : Bioactive compounds of A. racemosus were extracted based on the TCMSP, PCIDB, and BATMAN-TCM database. The potential targets of bioactive compounds were collected using target fishing. Epilepsy and comorbid dementia genes were collected from DISGENET. A PPI network among these targets was constructed using the intersecting key targets between herb targets and disease targets. Besides, DAVID bioinformatics resource was utilized for the pathway enrichment analysis on GO and KEGG. Ultimately, phytochemical compound-target genes-Pathways network has been assembled utilizing Cytoscape to decipher the mechanism of the herb. Results: The network analysis revealed that 5 targets (CASP3, TNF, VEGFA, PTGS2 and CNR1) might be the key therapeutic targets of asparagus on Epilepsy comorbid Alzheimer's disease. Based on high connectivity, four hub compounds with the highest connectivity were noted and it includes Shatavarin V, Sarsasapogenin, Shatavarin IX, and Shatavarin VI. A total of 19 KEGG terms were enriched as the potential pathways of A. racemosus in Epilepsy comorbid Alzheimer's disease. Conclusion: This study envisaged the pharmacological and molecular mechanism of A. racemosus against epilepsy comorbid Alzheimer's disease and put forward a strategy to uncover the mechanisms of Traditional Indian Medicine based on network pharmacology. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00169-x.

Antidepressant-like effect of a standardized hydroethanolic extract of Asparagus adscendens in mice.

OBJECTIVE: Asparagus adscendens Roxb. (Liliaceae), a traditional herbal medicine, has been used as an aphrodisiac and brain tonic in Asian countries. The aim of the present study is to investigate the antidepressant-like effect of standardized hydroethanolic extract of A. adscendens root and its possible mechanisms. MATERIALS AND METHODS: Mice administered with vehicle, imipramine (15 mg/kg/day; i.p.), and A. adscendens extract (AAE) (25, 50, and 100 mg/kg/day; i.p.) for 14 days were subjected to behavioral tests including forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) on the 14th day. In order to explore the underlying mechanism behind an antidepressant effect of AAE, the brain monoamine levels, oxidative stress parameters, and serum corticosterone levels were monitored. RESULTS: Our results indicated that pretreatment of AAE (25, 50, and 100 mg/kg) for 14 days statistically significantly (P < 0.01) demonstrated antidepressant-like effect as evidenced by reduced immobility time in both FST (105, 78.6, and 53.6 s) and TST (97.6, 73.5, and 54.67 s), with no significant change in spontaneous locomotor activities as observed in OFT. Further, the behavioral improvement was supported by the statistically significantly (P < 0.05) enhanced levels of monoamines and reduced corticosterone level along with amelioration of oxidative stress in AAE-treated animals as compared to vehicle control group. Conclusion: Our findings clearly demonstrated the antidepressant-like effect of AAE, which might have been mediated through the modulation of monoaminergic system and by regulating hypothalamic-pituitary-adrenal axis with amelioration of oxidative stress.

Differential content of secondary metabolites in diploid and tetraploid cytotypes of Siegesbeckia orientalis L.

Siegesbeckia orientalis L. is an annual herb widely distributed throughout the world and has many medicinal properties. In Chinese traditional system, it is popularly known as Xi-Xian and used for its anti-inflammatory properties. In the present study, two cytotypes (diploid and tetraploid) have been investigated for their secondary metabolites. The different plant parts have been explored in terms of total phenolics, total flavonoids, DPPH radical scavenging acitivity and total antioxidant capacity. Out of different plant parts, leaves have the maximum amount of secondary metabolites and antioxidant potential. HPTLC technique has been applied to quantify six marker compounds in the two cytotypes. Tetraploid cytotype has been compared with diploid cytotype, which shows that tetraploid has the maximum amount of studied secondary metabolites with high antioxidant potential.

Ferulic Acid Supplementation for Management of Depression in Epilepsy.

Neuroinflammation driven altered neurochemical milieu have been reported to play a significant role in pathogenesis of comorbid depression in epilepsy. Most of the antiepileptic drugs (AEDs) such as levetiracetam, taigabine, topiramate have not been reported any significant effect in alleviating neuroinflammation, which may explain their ineffectiveness in ameliorating depression associated with epilepsy. The supplementation of antidepressants (ADs) attracts various pharmacokinetic and pharmacodynamic interactions with AEDs and was considered unsafe in epilepsy. This scenario pushes us to search therapies beyond ADs by critically exploring the disease mechanism. Thus, as suggested by our previous findings, anti-inflammatory phytotherapy (Ferulic acid) appears a promising adjuvant therapy with levetiracetam for effective and safe management of depression associated with epilepsy. Pentylenetetrazole kindling induced epileptic animals were treated with vehicle, levetiracetam (40 mg/kg/day i.p.) and levetiracetam in combination with two doses of ferulic acid (40, 80 mg/kg)/day/p.o. for 15 days. Every 5th day during the treatment, depression was evaluated and animals were administered pentylenetetrazole to evaluate the effect of different pharmacological interventions on seizure severity. The epileptic animals were reported decreased seizure threshold associated with comorbid depression. The treatment with levetiracetam was found ineffective in ameliorating the associated depression. However ferulic acid supplementation with levetiracetam ameliorated comorbid depression supported with restored circulating corticosterone levels, decreased proinflammatory cytokines (IL-1ß, TNF-α) and indoleamine 2,3-dioxygenase activity in mice brain. Thus, suggesting supplementation of anti-inflammatory phytomolecules such as ferulic acid as safe and effective adjuvant therapy for the management of comorbid depression in epilepsy.

Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn.

ETHNOPHARMACOLOGICAL RELEVANCE: Root powder of Achyranthes aspera Linn. (A. aspera) belongs to family Amaranthaceae is used in Indian traditional medicine for the management of epilepsy and its efficacy is widely acclaimed among the different rural communities. AIM OF THE STUDY: The present study was aimed to establish the possible anticonvulsant effect of A. aspera methanolic root extract using acute anticonvulsant models and to evaluate the acute toxicity and neurotoxic potential A. aspera extract. MATERIAL AND METHODS: A. aspera methanolic extract was standardized with respect to betaine using HPTLC. The maximal electroshock (MES), pentylenetetrazol (PTZ), picrotoxin and bicuculline induced seizure models were used to evaluate the anticonvulsant potential of standardized A. aspera root extract. The GABA content in cortex and hippocampus of extract treated mice was evaluated using HPLC. Moreover, the animals were also evaluated for acute toxicity study and neurotoxicity test. RESULTS: A significant enhancement in the seizure threshold was observed by A. aspera extract (5 and 10mg/kg) treated mice in PTZ, picrotoxin and bicuculline models as compared to saline treated mice respectively, whereas the extract failed to show protection in MES induced seizures. Moreover, A. aspera treatment (5 and 10mg/kg) significantly enhances the GABA levels in hippocampus and cortex as compared to saline treated group. A. aspera root extract was devoid of any sign of acute toxicity as well as neurotoxicity. CONCLUSIONS: A. aspera root extract exhibits significant anticonvulsant effect by facilitation of GABAergic neurotransmission in the brain.

Adjuvant neuronal nitric oxide synthase inhibition for combined treatment of epilepsy and comorbid depression.

BACKGROUND: Elevated nitric oxide (NO) levels in the brain have been apparently associated with depression in kindled animals. Owing to the major role of neuronal nitric oxide synthase (nNOS) in brain and ineffectiveness of antiepileptic drugs (AEDs) in restoring nitrosative stress, the present study was envisaged to evaluate the adjuvant nNOS inhibitor, 7-nitroindazole (7-NI) with valproic acid for combined treatment of epilepsy and associated depression. METHODS: Pentylenetetrazole kindled animals associated with depression were treated with vehicle, valproate (300mg/kg/day ip), valproate with 7-NI (10mg/kg; 20mg/kg; 40mg/kg)/day ip and 7-NI (40mg/kg/day ip) for 15days. Except naïve, all groups were challenged with pentylenetetrazole (35mg/kg ip) on days 5, 10, and 15 to evaluate seizure severity. Depression was evaluated in all experimental groups using the tail suspension and forced swim test on days 1, 5, 10 and 15. On day 15, biochemical (corticosterone levels) and neurochemical (serotonin, kynurenine, tryptophan, glutamate, GABA, nitrite levels) estimations were carried out in cortical and hippocampal area of mice brain. RESULTS: Vehicle treated kindled animals were significantly associated with depression. Chronic valproate treatment in kindled animals significantly reduced seizure severity, but could not reverse associated depression. 7-NI per se treatment in kindled animals was also reported unable to restore the associated depression completely. However, 7-NI supplementation with valproate significantly reduced seizure severity score and completely ameliorated depression with restoration of altered biochemical and neurochemical milieu. CONCLUSION: Adjuvant nNOS inhibition can be previewed as safe therapy with AEDs for the combined management of epilepsy and associated depression.

Asparagus adscendens root extract enhances cognition and protects against scopolamine induced amnesia: An in-silico and in-vivo studies.

Asparagus adscendens Roxb. commonly known as safed musli and belonging to the Liliaceae family is cultivated mainly in Asian countries. In traditional medicine, safed musli is recommended as nerve tonic and remedy for memory impairment. The present study was aimed to evaluate nootropic and antiamnesic activities of Asparagus adscendens extract (AAE) using in silico and in vivo approach. Phytoconstituents of A. adscendens root reported in literature were subjected to in silico prediction using PASS and Pharmaexpert. The radial arm maze and passive shock avoidance paradigm were employed to evaluate nootropic activity. Subsequently, the anti-amnesic activity was evaluated in scopolamine induced amnesia model. To elucidate the mechanism of nootropic activity, the effect of AAE on the activities of acetylcholinesterase and antioxidant enzymes in the cortex and hippocampus of mice were also evaluated. In silico activity spectrum for all of A. adscendens phytoconstituents exhibited excellent prediction score for nootropic activity. Pretreatment with AAE (50, 100 & 200 mg/kg, i.p.) for 15 days showed significant decrease in working memory error, reference memory error and retrieval latency in radial arm maze and decrease in step down latency in passive shock avoidance paradigm were observed. Further, AAE significantly reduced acetylcholinesterase and oxidative stress parameters in cortex and hippocampus of mice. Thus, in silico and in vivo results suggest that A. adscendens root may exert its nootropic activity through both anti-acetylcholinesterase and antioxidant activities.

Evidence in support of using a neurochemistry approach to identify therapy for both epilepsy and associated depression.

The present study aimed to develop a neurochemistry-based single or adjuvant therapy approach for comprehensive management of epilepsy and associated depression employing pentylenetetrazole-kindled animals. Kindling was induced in two-month-old male Swiss albino mice by administering a subconvulsant pentylenetetrazole dose (35mg/kg, i.p.) at an interval of 48±2h. These kindled animals were treated with saline and sodium valproate (300mg/kg/day, i.p.) for 15days. Except for the naïve group, all other groups were challenged with pentylenetetrazole (35mg/kg, i.p.) on days 5, 10, and 15 to evaluate the seizure severity. Depression was evaluated in all experimental groups after normalization of locomotor activity, using tail suspension and forced swim test on days 1, 5, 10, and 15. Four hours after behavioral evaluations on day 15, all animals were euthanized to collect their serum and discrete brain parts. Corticosterone levels were estimated in all the experimental groups as a marker of a dysregulated hypothalamus pituitary adrenal axis. Neurochemical alterations (norepinephrine, dopamine, tryptophan, kynurenine, serotonin, glutamate, GABA, and total nitrate levels) were also estimated in the cortical and hippocampal areas of the mouse brain. Results revealed that saline-treated kindled animals were associated with significant depression and altered neurochemical milieu in comparison with naïve animals. Chronic valproate treatment in kindled animals significantly reduced seizure severity score bud did not ameliorate associated depression or completely restore altered biochemical and neurochemical milieu. Based on the observation of neurochemical changes in all the groups, we propose that restoration of altered neurochemical milieu, elevated indoleamine 2,3-dioxygenase enzyme activity, and corticosterone levels using pharmacological tools with/out valproic acid may be explored for management of both epilepsy and comorbid depression.

Adjuvant indoleamine 2,3-dioxygenase enzyme inhibition for comprehensive management of epilepsy and comorbid depression.

Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. Alteration of tryptophan metabolism towards kynurenine pathway may be one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme (responsible for shifting tryptophan metabolism) employing minocycline with valproic acid for comprehensive management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive dose (35mg/kg, i.p.) at an interval of 48±2h. Kindled animals were treated with saline, valproate (300mg/kg/day i.p.), valproate in combination with different doses of minocycline (10mg/kg; 20mg/kg; 40mg/kg)/day i.p. and minocycline per se (40mg/kg/day i.p.) for 15 days. Except naïve, all the groups were challenged with pentylenetetrazole (35mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using tail suspension and forced swim test on days 1, 5, 10 and 15, 2h after pentylenetetrazole challenge. Results suggested that saline treated kindled animals were significantly associated with depression. Chronic valproate treatment significantly reduced seizure severity score but unable to ameliorate the associated depression. Minocycline supplementation with valproic acid dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of IDO enzyme inhibitors with valproic acid could be explored further for comprehensive management of epilepsy and associated depression.

Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities.

Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L.

ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes aspera (A. aspera) has been used as a brain tonic in folk medicine. Although, ethnic use of medicinal plant has been basis for drug discovery from medicinal plants, but the available in-silico tools can be useful to find novel pharmacological uses of medicinal plants beyond their ethnic use. AIM OF THE STUDY: To validate in-silico prediction for novel nootropic effect of A. aspera by employing battery of tests in mice. MATERIAL AND METHODS: Phytoconstituents of A. aspera reported in Dictionary of Natural Product were subjected to in-silico prediction using PASS and Pharmaexpert. The nootropic activity predicted for A. aspera was assessed using radial arm maze, passive shock avoidance and novel object recognition tests in mice. After behavioral evaluation animals were decapitated and their brains were collected and stored for estimation of glutamate levels and acetylcholinesterase activity. RESULTS: In-silico activity spectrum for majority of A. aspera phytoconstituents exhibited excellent prediction score for nootropic activity of this plant. A. aspera extract treatment significantly improved the learning and memory as evident by decreased working memory errors, reference memory errors and latency time in radial arm maze, step through latency in passive shock avoidance and increased recognition index in novel object recognition were observed, moreover significantly enhanced glutamate levels and reduced acetylcholinesterase activity in hippocampus and cortex were observed as compared to the saline treated group. CONCLUSION: In-silico and in-vivo results suggest that A. aspera plant may improve the learning and memory by modulating the brain glutamatergic and cholinergic neurotransmission.

Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity.

The present study was envisaged to investigate the neuroprotective potential of Allium cepa (A. cepa) in aluminium chloride induced neurotoxicity. Aluminium chloride (50 mg/kg/day) was administered orally in mice supplemented with different doses of A. cepa hydroethanolic extract for a period of 60 days. Various behavioural, biochemical and histopathological parameters were estimated in aluminium exposed animals. Chronic aluminium administration resulted in significant motor incoordination and memory deficits, which were also endorsed biochemically as there was increased oxidative stress as well as elevated acetylcholinesterase (AChE) and aluminium levels in the brain. Supplementation with A. cepa in aluminium exposed animals significantly improved muscle coordination and memory deficits as well as reduced oxidative stress, AChE and decreased abnormal aluminium deposition in the brain. Histopathologically, there was marked deterioration visualized as decreased vacuolated cytoplasm as well as decreased pyramidal cells in the hippocampal area of mice brain which were found to be reversed with A. cepa supplementation. Administration of BADGE (PPARγ antagonist) in aluminium exposed animals reversed the neuroprotective potential of A. cepa as assessed with various behavioural, biochemical, neurochemical and histopathological estimations. In conclusion, finding of this study suggested significant neuroprotective potential of A. cepa in aluminium induced neurotoxicity. Further, the role of PPARγ receptor agonism has also been suggested as a putative neuroprotective mechanism of A. cepa, which needs further studies for confirmation.

Revealing Medicinal Plants That Are Useful for the Comprehensive Management of Epilepsy and Associated Comorbidities through In Silico Mining of Their Phytochemical Diversity.

In silico techniques in drug discovery may rationalise and speed up the identification of lead molecules from nature. Drug discovery from medicinal plants has mostly been confined to indications in accordance with their ethnical use only. However, the availability of multiple phytoconstituents in medicinal plants suggests that these may be much more useful beyond their traditional uses and in the management of chronic diseases, along with their comorbidities. In this study, the computer programmes PASS and PharmaExpert were used to reveal the medicinal plants useful in the comprehensive management of epilepsy and associated psychiatric disorders based on the pleiotropic effects predicted for their phytoconstituents. In silico analysis revealed that seven of 50 medicinal plants from traditional Indian medicine possessed the desired pleiotropic effect, i.e., anticonvulsant, antidepressant, and nootropic activities. The majority of phytoconstituents from Passiflora incarnata were concurrently predicted to have the desired pleiotropic effects. Therefore, P. incarnata was pharmacologically validated using the pentylenetetrazole kindling mouse model. Behavioural and neurochemical evaluations confirmed the ameliorative role of P. incarnata in epilepsy and the associated depression and memory deficit. The pharmacological findings from this study propose that PASS and PharmaExpert may serve as good tools for the optimisation of the selection of plants based on their phytoconstituents for the treatment of different ailments, even beyond their traditional use.

Meiotic studies in some species of tribe Cichorieae (Asteraceae) from Western Himalayas.

The present paper deals with meiotic studies in 15 species belonging to 6 genera of the tribe Cichorieae from various localities of Western Himalayas. The chromosome number has been reported for the first time in Hieracium crocatum (2n = 10) and Lactuca lessertiana (2n = 2x = 16). Further, intraspecific variability has been reported for the first time in H. umbellatum (2n = 2x = 10 and 2n = 6x = 54), Tragopogon dubius (2n = 2x = 14 and 2n = 4x = 28), and T. gracilis (2n = 2x = 14). The chromosome report of 2n = 2x = 10 in Youngia tenuifolia is made for the first time in India. Maximum numbers of the populations show laggards, chromosome stickiness, and cytomixis from early prophase to telophase-II, leading to the formation of aneuploid cells or meiocytes with double chromosome number. Such meiotic abnormalities produce unreduced pollen grains and the reduced pollen viability.

Ficus religiosa L. figs--a potential herbal adjuvant to phenytoin for improved management of epilepsy and associated behavioral comorbidities.

Oxidative stress, together with mitochondrial dysfunction, has been reported to be involved in the pathogenesis of epileptogenesis and its associated comorbidities. Phytoflavonoids have shown numerous beneficial ameliorative effects on different neurological disorders by virtue of their antioxidant effect. The present study investigated the effect of flavonoid-rich ethyl acetate fraction of the crude fig extract of Ficus religiosa in combination with phenytoin on seizure severity, depressive behavior, and cognitive deficit in pentylenetetrazol (PTZ)-kindled mice. The flavonoid-rich ethyl acetate fraction of the crude fig extract was found to show significant antioxidant potential in various in vitro free radical scavenging assays. Combined treatment of this fraction (2.5, 5, and 10 mg/kg; i.p.) along with a subeffective dose of phenytoin (15 mg/kg; i.p.) in postkindled animals once daily for fifteen days showed a dose-dependent decrease in the seizure severity score, a decreased number of mistakes, increased step-down latency in passive shock avoidance paradigm, and decreased immobility time in the tail suspension test in comparison with the phenytoin only-treated group. Biochemical investigations of the brain tissue showed amelioration of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, and reduced catalase and acetylcholinesterase (AChE) activities, thereby indicating suppression of oxidative stress. In conclusion, the results of the present study showed the protective effect of the flavonoid-rich fraction of F. religiosa along with a subeffective dose of phenytoin in PTZ-kindling-associated cognitive deficit and depressive behavior with complete suppression of seizures through reduction of oxidative stress, supporting the the need for clinical evaluation of the supplementation of phytoflavonoids along with antiepileptic drugs (AEDs) for management of epilepsy and its psychiatric and cognitive comorbidities.

Revealing pharmacodynamics of medicinal plants using in silico approach: a case study with wet lab validation.

BACKGROUND: Exploration of therapeutic mechanism is an integral part of medicinal plant based drug discovery for better understanding of pharmacological behavior of these agents. But, its study using conventional hit and trial wet laboratory experiments proves to be very tedious, time consuming and expensive, thus encouraging development of in silico techniques. Hence, an in silico technique has been devised using a computer software Prediction of Activity Spectra for Substances (PASS) to study pharmacodynamics of medicinal plants. The technique has been presented with a case study using Ficus religiosa L. (Moraceae) in which its anticonvulsant mechanism has been elucidated with PASS and further validated experimentally. METHODS: Pentylenetetrazol (PTZ)-induced convulsion test was used to study the anticonvulsant effect of standardized bark extract of F. religiosa. Thereafter, structure of all the reported bioactive metabolites in the bark was subjected to PASS software to obtain biological activity spectrum of each compound. The mechanism signifying anticonvulsant effect was selected from the spectrum and was further validated using in vitro test. RESULTS AND DISCUSSION: The extract showed significant anticonvulsant effect in PTZ test. PASS analysis showed a high activity score for GABA aminotransferase (GABA-AT) inhibitory effect of the bioactive metabolites present in the bark. In vitro GABA-AT enzyme assay results were in concordance with the predicted mechanism by PASS for the observed anticonvulsant effect, as the extract showed potent inhibition of the enzyme. The results of present study showed the in silico technique to be useful for elucidation of unknown therapeutic mechanisms of medicinal plants.

Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice.

Epilepsy is a chronic neurological disorder and generally associated with certain psychiatric comorbidities. Among several comorbidities depressive behavior and cognitive impairment has been reported to be most debilitating comorbidity associated with epilepsy. This study was envisaged to evaluate the ameliorative effect of Curcumin on depression like behavior and cognitive impairment observed in pentylenetetrazole kindled animals. Male Swiss Albino mice were kindled with subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.). Successfully kindled animals were used in the study to observe the effect of different treatments. Treatment groups received phenytoin (30 mg/kg) and Curcumin (50, 100 and 200mg/kg) for 15 days. The animals were challenged with pentylenetetrazole (35 mg/kg, i.p.) on day 5, 10 and 15 and seizure severity score, immobility period, number of mistakes and step down latency were recorded. On 15th day, all the animals were sacrificed after behavioral evaluations and their brain was isolated and homogenized to estimate brain norepinephrine, serotonin, total nitrite level and acetylcholinesterase activity. Phenytoin treatment significantly improved the depressive like behavior along with its anticonvulsant effect, however was unable to improve memory impairment. Curcumin significantly attenuated seizure severity, depression like behavior and memory impairment in kindled animals, in dose dependent manner. These results were supported by the biochemical modulation of brain monoamine, nitrosative stress level and acetylcholinesterase activity. Thus present study concluded that Curcumin has the ameliorative effect on seizure severity, depression like behavior and memory impairment in pentylenetetrazole kindled mice, possibly via central monoaminergic modulation and inhibitory effect on nitrosative stress and acetylcholinesterase activity.

Effect of saponin fraction from Ficus religiosa on memory deficit, and behavioral and biochemical impairments in pentylenetetrazol kindled mice.

In our previous study, the saponin-rich fraction (SRF) of adventitious root extract of Ficus religiosa L. (Moraceae) was shown to have an anticonvulsant effect in acute animal models of convulsions. The present study was envisaged to study the effect of SRF in the pentylenetetrazol (PTZ) kindling mouse model and its associated depression and cognition deficit. Treatment with the SRF (1, 2 and 4 mg/kg; i.p.) for 15 days in kindled mice significantly decreased seizure severity on days 5, 10 and 15 when challenged with PTZ (35 mg/kg; i.p.). Marked protection against kindling-associated depression was also observed on days 10 and 15 in the SRF-treated groups when tested using the tail-suspension test. However, the SRF treatment failed to protect kindling-associated learning and memory impairments in the passive shock avoidance paradigm. The observed behavioral effects were corroborated with modulation in the levels of noradrenaline, dopamine, serotonin, GABA and glutamate in discrete brain regions.

Gastroprotective effect of Acacia nilotica young seedless pod extract: role of polyphenolic constituents.

OBJECTIVE: To systematically evaluate antiulcer potential of Acacia nilotica in different ulcer models in rats. METHODS: Different extracts [ethanolic, 50% hydroethanolic (50:50), 70% hydroethanolic (70:30) and aqueous] of young seedless pods were examined in pylorus ligation induced gastric ulcers in rats. Various parameters like, volume of gastric acid secretion, pH, free acidity, total acidity, ulcer index, mucin content and antioxidant studies were determined and were compared between extract treated, standard and vehicle control following ulcer induction. The most active extract was also evaluated in swimming stress induced and NSAID induced gastric ulceration. RESULTS: Among different extracts of young seedless pods only hydroethanolic extracts showed significant antiulcer activity in pyloric ligation induced ulceration. Even more the 70% hydroethanolic extract showed better protection as compared to 50% hydroethanolic extract. Further 70 % hydroethanolic extract also showed significant mucoprotection in swimming stress induced and nonsteroidal antiinflammatory drugs induced gastric ulceration. CONCLUSION: The results of present study concluded that the hydroethanolic extract of young seedless pods of Acacia nilotica has antiulcer activity in pylorus ligation, swimming stress and NSAID induced rat ulcer models. The extract containing more amount of phenolic components show high antiulcer activity, indicating the phenolic component of the extract to be responsible for the activity of the extracts.