Debjani Guha

Inhibitory role of Acorus calamus in ferric chloride–induced epileptogenesis in rat

The roots and rhizomes of Acorus calamus (Family: Araceae) have been used in the ancient systems of medicine for the treatment of various neurological disorders. Of the various methods used for inducing experimental epileptic models, the intracortical administration of ferric chloride (FeCl3) into sensorimotor cortex induces recurrent seizures and epileptic discharge similar to human post-traumatic epilepsy through the generation of free radicals. The present study focuses on the effect of Acorus calamus on the behavioral, electroencephalographic, and antioxidant changes in FeCl3-induced rat epileptogenesis. Topical administration of FeCl3 (5 μL; 100 mM) into the sensorimotor cortex of rats showed an increase in the wet dog shake behavior, spike wave discharges together with an significant increase in antioxidant enzyme activity, such as superoxide dismutase and catalase, resulting in an increase in the level of lipid peroxidation in cerebral cortex. Pretreatment with Acorus calamus (200 mg/kg b.w., p.o. for 14 days) and also diazepam (DZ, 20 mg/kg b.w., i.p.) decreased the WDS behavior, spike wave discharges with single isolated positive waves, and a significant decrease in activity of superoxide dismutase and level of lipid peroxidation was observed in cerebral cortex with respect to those observed in FeCl3-induced epileptic group. Data presented in this study clearly show that Acorus calamus possesses the ability for preventing the development of FeCl3-induced epileptogenesis by modulating antioxidant enzymes, which in turn exhibit the potentiality of Acorus calamus to be developed as an effective anti-epileptic drug.

Moringa oleifera induced potentiation of serotonin release by 5-HT3 receptors in experimental ulcer model

ETHNOPHARMACOLOGICAL RELEVANCE moringa oleifera (Moringaceae), a perennial plant is widely cultivated throughout the world. Extensive pharmacological studies revealed its promising role in modulation of various disorders like antispasmodic, diuretic, abortifacient, antimicrobial antibacterial, antitubercular, antiviral, antifertility, depressant, anti-inflammatory and anticancer property which promoted us to conduct the study to elucidate its role on experimental gastric ulceration. AIM OF THE STUDY the aim of the present study was to assess the efficacy of its aqueous leaf extract on protection of gastric ulceration and characterize the possible modulatory mechanism underlying the phenomenon. MATERIALS AND METHODS adult Holtzman strain albino rats (weight 150-200 g) of either sex were used for the study. Ulceration was induced using aspirin (500 mg/kg body weight) and using Moringa oleifera (MO), a herbal formulation, the modulatory mechanism has been studied and compared with a commonly used antagonist of 5-HT(3) receptors, ondansetron by assessing parameters like mean ulcer index, 5-HT content, EC cell count and mucosal thickness. RESULTS the results of our study suggest that MO protects ulcer formation by modulating 5-HT secretion through EC cell via 5-HT(3) receptors in gastrointestinal tract. INTERPRETATION AND CONCLUSION MO showed maximum protective activity at a dose of 300 mg/kg body weight against above-mentioned experimental rat ulcer model by modulating 5-HT secretion through EC cell via 5-HT(3) receptors in gastrointestinal tract which has given a glimpse of a therapeutic approach for gastric ulcer management, which may be beneficially used in contrast to the classical antacid, antihistamine or surgical treatment. Further investigations and proper screening regarding various phytochemicals, alkaloids present within MO leaf will help to formulate effective herbal preparation that will be used to combat gastrointestinal disorders in future.

Effect of chronic administration of Acorus calamus on electrical activity and regional monoamine levels in rat brain

Effect of chronic administration of ethanolic extract of Acorus calamus (AC) was studied on spontaneous electrical activity and monoamine levels of brain. AC (200 mg/kg and 300 mg/kg) was administered orally to adult Holtzman strain rats for 14 days. In AC treated rats, electrographic recording revealed that there was increase in α activity together with an increase in norepinephrine level in the cerebral cortex but a decrease in the midbrain and cerebellum. Serotonin level was increased in the cerebral cortex but decreased in the midbrain. Similarly, dopamine level was increased in the caudate nucleus and midbrain but decreased in the cerebellum. Thus AC seems to exert its depressive action by changing electrical activity and by differentially altering brain monoamine levels in different brain regions.

A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular colchicine injection

Abstract Colchicine induces neurodegeneration, but the extent of neurodegeneration in different areas of the brain in relation to neuroinflammation remains unclear. Such information may be useful to allow for the development of a model to compare colchicine-induced neurodegeneration with other neurodegenerative diseases such as Alzheimer’s Disease (AD). The present study was designed to investigate the extent of neurodegeneration along with neuroinflammation in different areas of the brain, e.g. frontal cortex, parietal cortex, occipital cortex, corpus striatum, amygdala and hippocampus, in rats along with memory impairment 21 days after a single intracerebroventricular (icv) injection of colchicine. Memory parameters were measured before and after icv colchicine injection in all test groups of rats (control, sham-operated, colchicine-injected [ICIR] rats). On Day 21 post-injection, rats from all groups were anesthesized and tissues from the various brain areas were collected for assessment of biomarkers of neuroinflammation (i.e. levels of ROS, nitrite and proinflammatory cytokines TNFα and IL-1β) and neurodegeneration (assessed histologically). The single injection of colchicine resulted in impaired memory and neurodegeneration (significant presence of plaques, Nissl granule chromatolysis) in various brain areas (frontal cortex, amygdala, parietal cortex, corpus striatum), with maximum severity in the hippocampus. While IL-1β, TNFα, ROS and nitrite levels were altered in different brain areas in the ICIR rats, these parameters had their greatest change in the hippocampus. This study showed that icv injection of colchicine caused strong neurodegeneration and neuroinflammation in the hippocampus of rats and the increases in neurodegeneration were corroborated with those of neuroinflammation at the site. The present study also showed that the extent of neurodegeneration and neuroinflammation in different brain areas of the colchicine-injected rats were AD-like and supported the fact that such rats might have the ability to serve as a sporadic model of AD.

Suppression of penicillin-induced epileptiform activity by Nigella sativa : Possible mediation by neurotransmitters

Nigella sativa (NS), an endogenous plant of family Ranunculaceae, exhibits a wide range of biological activity. This report explores the effect of aqueous extract of NS seeds on penicillin-(PCN-100 IU in 100 μl) induced epileptic rat model. Oral pretreatment of NS (250 mg/kg) suppressed PCN-induced seizure considerably, reduced spike-wave discharges and occurrence of generalized tonic–clonic seizures. Electroencephalographic data showed NS pretreatment to experimental animals elicited 85% abolition of high voltage spike discharges. NS pretreatment resulted in elevation of serotonin (5-HT) level and decreased dopamine (DA) level in cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN) and midbrain (MB). A significant decrease in norepinephrine (NE) level was observed only in the CC. The present study suggests that chronic administration of NS protects PCN-induced generalized epilepsy by selectively altering the monoamine level in different brain regions. The seizure abolition observed in the NS pretreated rats was comparable to the anticonvulsive pattern exhibited by diazepam. The results suggest that NS has promising anticonvulsant action.

Gastric mucosal protection by aegle marmelos against gastric mucosal damage: role of enterochromaffin cell and serotonin.

Background/Aims: Serotonin (5-hydroxytryptamine; 5-HT) released from enterochromaffin (EC) cells in gastric mucosa inhibits gastric acidity by increasing the gastric mucus secretion. In the present study, we evaluated the effect of aqueous extract of Aegle marmelos (AM) ripe fruit pulp (250 mg/kg body weight) on mean ulcer index (MUI), EC cells, 5-HT content, and adherent mucosal thickness of ulcerated gastric tissue in adult albino rats. Material and Methods: Ulceration was induced by using aspirin (500 mg/kg, p.o.), cerebellar nodular lesion and applying cold-restraint stress. Results: In all cases increased MUI in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content and adherent mucosal thickness (P < 0.05). Pretreatment with AM for 14 days decreased MUI, increased EC cell count, and 5-HT content as well as adherent mucosal thickness in all ulcerated group (P < 0.05). Conclusion: AM produces gastric mucosal protection mediated by increased EC cell count and 5-HT levels.

The role of Acorus calamus in the involvement of monoaminergic and electroencephalographic activities of amygdala kindled rats

The development of amygdaloid kindling was assessed following preconditioning with Acorus calamus (AC) of the chronically prepared rats. The result demonstrated that chronic treatment with AC (200 mg/kg, p.o.) significantly decreased epileptogenesis. The number of kindling trials required to reach the generalized convulsions was significantly decreased by pretreatment with AC in comparison with kindled animals. Preconditioning the kindled animals with AC for 14 days markedly reduced the development of amygdaloid seizure, intensity of fit and duration of after-discharge together with an increase in the norepinephrine, serotonin and decrease in dopamine content in discrete brain regions. Analysis of behavioural studies indicated a significant decrease in seizure stages and duration of amygdaloid afterdischarges. These results reveal that AC possibly modifies the brain functions by modulating the brain monoamines and behavioural as well as electrographic discharges. Results from this study suggest that AC functions by focal sensitization of monoamines mediated inhibitory mechanism and reflecting the inhibitory influence of AC in regulating the development and attenuation of epileptic states.

Monoaminergic correlates of penicillin-induced epilepsy

A neurochemical basis for many of the epilepsies has long been suspected to result from an imbalance between the various neurotransmitter mechanisms. The present study was undertaken to gain an understanding of the brain neurotransmitter involvement in experimental epilepsy. Adult male Holtzman strain rats were subjected to convulsions triggered by intracortical (somatosensory cortex) penicillin (PCN) administration (100 IU, 100 μl) and the regional brain levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed in epileptic rats. The results of the study revealed a decrease in the NE level in the cerebral cortex (cc), cerebellum (cb), caudate nuclei (cn) and midbrain (mb) except an increment in the chronic cortical NE. On the other hand DA level had increased significantly in the cc and mb though in the cb and cn the level had lowered. 5-HT levels were decreased in the cb, cn and mb while in the cc an enhanced level of 5-HT was observed. The results obtained clearly show that the nervous structures tested with PCN had a different neurotransmitter response pattern which significantly changed along the cortico-cerebellar axis.

Effect of Moringa oleifera root extract on penicillin-induced epileptic rats

Effect of chronic treatment of aqueous extract root extract of Moringa oleifera (350 mg/kg) on penicillin-induced convulsion and the changes of EEG pattern and brain serotonin (5-HT), dopamine (DA) and norepinephrine (NE) level were studied in Holtzman strain adult albino rats of both sexes. The results revealed that pretreatment with Moringa oleifera (MO) inhibited penicillin-induced seizure and decreased the number and duration of spike wave discharges. Moringa oleifera significantly increased the NE level in cerebral cortex (CC) and midbrain (MB) and decreased that in the cerebellum (CB). Similarly, dopamine level significantly increased in MB and CB and decreased in CC and caudate nucleus (CN) and 5-HT level significantly increased in all four brain regions. Thus Moringa oleifera suppresses penicillin-induced epileptic seizure by changing the electrical activity and by altering the 5-HT, norepinephrine and dopamine balance.