Acteoside Isolated from Colebrookea oppositifolia Smith Attenuates Epilepsy in Mice Via Modulation of Gamma-Aminobutyric Acid Pathways.

The present study was aimed to evaluate the anticonvulsant activity of acteoside and explore its mechanism of action. Initially, the acteoside was evaluated in maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions, and later it was evaluated against N-methyl-D-aspartic acid (NMDA)-induced mortality in Swiss albino mice. Based on the response in these models, further evaluations were performed to explore the mechanism of action. In the results, the acteoside (10, 25, and 50 mg/kg) has shown significant anticonvulsant activity in the PTZ model (p < 0.01 for all doses); however, there was no protection observed in MES and NMDA models. Therefore, further mechanism-based studies were performed on the PTZ model, and the outcomes have revealed that there was a significant reduction in GABA (p < 0.01 for both regions) and elevation of glutamate (p < 0.01 for both regions) in the cortex and hippocampus regions of PTZ-treated animals. Further, the antioxidant levels (SOD, catalase, GPx, GR, GSH, LPO) were altered significantly (p < 0.01 for all parameters), with reduced GABAA mRNA levels (p < 0.01) in the PTZ control compared with the normal control. Interestingly, co-administration of acteoside (25 mg/kg) (p < 0.01 for all parameters) has restored all the PTZ-induced alterations compared to PTZ-control. Moreover, the anti-PTZ action of acteoside was completely blocked in the presence of flumazenil, and thus confirmed the GABAergic mechanism behind the anticonvulsant activity of acteoside. Besides, actophotometer and rotarod tests have confirmed that the acteoside is free from central side effects like motor incoordination and locomotor deficits.

Correction to: Efficacy and safety of inhalation budesonide in the treatment of pediatric asthma in the emergency department: a systematic review and meta-analysis.

The original version of this article, published on 29 March 2020 unfortunately contains a mistake.

Efficacy and safety of inhalation budesonide in the treatment of pediatric asthma in the emergency department: a systematic review and meta-analysis.

BACKGROUND: This study was aimed to evaluate the beneficial role of inhalation budesonide(BUD) in improving the pulmonary functions, and reducing the hospital admission rate, worsening of asthma and commonly encountered adverse events in pediatric asthma. METHODS: The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases to identify the randomized control trials(RCTs). RESULTS: 21 RCTs involving 12,787 subjects were included. The meta-analysis revealed that the BUD has reduced the hospitalization rate (Mantel-Haenszel (M-H), random effects odd ratio (RE-OR) of 0.34, p = 0.003, I2 = 75%), and worsening of asthma (M-H, RE-OR 0.38, p = 0.001, I2 = 73%); significantly improved the pulmonary functions such as FEV1 (Inverse variance (IV): 1.05, p < 0.0001, I2 = 94%), PEFR (IV: 1.40, p < 0.0001, I2 = 87%), morning PEF (IV: 1.04, p < 0.0001, I2 = 91%), and evening PEF (IV: 1.29, p < 0.0001, I2 = 92%) compared to control. Further, the incidences of adverse events like Pharyngitis (M-H, RE-OR 0.88, at 95% CI, p = 0.69, I2 = 0%), Sinusitis (M-H, RE-OR 0.78, p = 0.79, I2 = 0%), Respiratory infections (M-H, RE-OR 0.96, p = 0.46, I2 = 0%), Otitis media (M-H, RE-OR 0.82, p = 0.32, I2 = 12%) and Fever (M-H, RE-OR 0.78, p = 0.64, I2 = 0%) were almost same between BUD and control. CONCLUSION: The outcomes of the meta-analysis suggest that high-dose inhalation BUD could benefit the pediatric patients in minimizing the worsening of asthma and hospitalization rate, along with improving the pulmonary functions, with negligible adverse drug reactions.

Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional system of Indian medicine, the whole plant and roots of Achyranthes aspera L have been extensively used to treat neurological conditions such as epilepsy and stroke by the various ethnic communities of India. AIM OF THE STUDY: The present study was aimed to evaluate the cerebroprotective potential of methanol extract of A. aspera aerial parts (MeAA). MATERIALS AND METHODS: Initially the MeAA was evaluated for total phenolic content and subjected to detailed liquid chromatography-mass spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines the effect of MeAA was evaluated on lipopolysaccharide-induced generation of reactive oxygen species, nitrite and tumor necrosis factor-α. Finally, the MeAA (400 and 800 mg/kg) was evaluated against ischemia-reperfusion (I/R)-induced brain injury in rats. In brief, male Wistar rats were allocated in to five groups (G-I to G-V, n = 10). G-I and G-II assigned as sham control and I/R control, and received only vehicle (carboxy methyl cellulose 0.5% w/v, 10 ml/kg, p.o.). G-III received quercetin (20 mg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800 mg/kg oral doses of MeAA, respectively. All the treatments were given orally for a period of seven days and the parameters such as functional (neurological, cognitive and motor), morphological (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation, cytokines), and histopathological evaluations of the brain tissue was performed. RESULTS: The MeAA exhibited 72.48 mg gallic acid equivalents/g of total phenolic content and the LC-MS/MS analysis showed acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA. In in vitro antioxidant assays, the MeAA showed good antioxidant activity with IC50 of 126.50 µg/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in FRAP and ORAC assays, respectively. Further, the MeAA significantly suppressed the generation of ROS, nitrite and TNF-α in LPS activated RAW 264.7 cell lines. Besides, sixty mins of global cerebral ischemia followed by 24 h of reperfusion produced considerable alterations in neurobehavioral functions in the I/R control group compared to sham control, with a significant reduction in catalase and superoxide dismutase enzyme activities. Moreover, there was a significant reduction in reduced glutathione levels with increased lipid peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the brain tissue revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeAA (800 mg/kg, p.o.) has offered significant protection against I/R-induced functional, morphological, biochemical and histopathological alterations in Wistar rats. CONCLUSIONS: These findings suggest that the MeAA possesses potent cerebroprotective action through its antioxidant and anti-inflammatory mechanisms.

Chemical characterization and cerebroprotective effect of methanolic root extract of Colebrookea oppositifolia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Colebrookea oppositifolia Smith is one of the extensively used plants to treat neurological conditions such as epilepsy by the various ethnic communities in sub-Himalayan regions of India such as Bhoxa, Tharu and nomadic Gujjars. AIM OF THE STUDY: This study was conducted to evaluate the cerebroprotective effect of C. oppositifolia methanolic root (MeCO) extract in Wistar rats. MATERIALS AND METHODS: The MeCO was characterized for total phenolic content and later subjected for detailed liquid chromatography-mass spectrometry analysis. Further, it was evaluated for in vitro antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power and oxygen radical absorbance capacity assays. In addition, the MeCO was investigated on generation of ROS, nitrite, and TNF-α in LPS-stimulated RAW 264.7 cell lines. Finally, the cerebroprotective effect of MeCO was examined against global ischemia and reperfusion (I/R)-induced brain injury in Wistar rats. Male Wistar rats were allocated in to five groups (G-I to G-V, n = 10). G-I and G-II served as sham control and I/R control, respectively, and received only vehicle (0.5% w/v carboxy methyl cellulose, 10 ml/kg, p.o.). G-III served as reference standard and received quercetin (20 mg/kg, p.o.). G-IV and G-V animals received 200 and 400 mg/kg oral doses of MeCO, respectively. All the treatments were given for a period of seven days and the parameters such as neurobehavioral (neurological, and cognitive), and motor functions, biochemical (enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, IL-10, ICAM-I), morphological (cerebral edema and infarct area) and histopathological evaluations were performed. RESULTS: The MeCO showed a total phenolic content of 137.28 mg gallic acid equivalents/g, and LC-MS/MS analysis of MeCO showed presence of acteoside, gossypin, quercetin and ferulic acid as major ingredients (6680.3, 1.55, 3.52 and 431.1 ng/mg). In in vitro antioxidant assays, the MeCO exhibited potent activity with IC50 of 49.10 µg/ml in DPPH assay; FRAP and ORAC values of 1180.5 and 2983.5 respectively. Furthermore, the MeCO significantly inhibited generation of ROS, nitrite and TNF-α in LPS-stimulated RAW 264.7 cell lines. Sixty min of global ischemia with 24 h reperfusion produced substantial alterations in neurobehavioral functions in the I/R control group compared to sham control. In addition, a significant reduction in catalase and superoxide dismutase activities was observed. Moreover, lipid peroxidation increased and reduced glutathione levels decreased significantly. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the rat brain revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeCO (200 and 400 mg/kg) alleviated all the I/R-induced perturbances (neurobehavioral, and motor functions, biochemical, morphological and histopathological) compared with the I/R control. CONCLUSIONS: The MeCO exhibit potent cerebroprotective activity through its potent antioxidant and anti-inflammatory mechanisms, and hence may be useful in the management of ischemic stroke and associated complications.

Ameliorative potential of Colebrookea oppositifolia methanolic root extract against experimental models of epilepsy: Possible role of GABA mediated mechanism.

BACKGROUND: Colebrookea oppositifolia Smith is one of the commonly used plants to treat epilepsy by various folk medicine communities like nomadic Gujjars, Tharu and Bhoxa in sub-Himalayan regions of India. PURPOSE: The present study was undertaken to evaluate the anticonvulsant activity of roots of Colebrookea oppositifolia using various experimental models of epilepsy in mice. METHODS: Petroleum ether extract of roots of C. Oppositifolia (PeCO), methanolic eCO (MeCO) and aqueous eCO (AeCO) was initially evaluated in six-hertz-seizure test in mice, the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on brain GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the possible locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. RESULTS: In six-hertz-seizure test the MeCO (25, 50, 100 and 200mg/kg) and AeCO (50, 100, 200, 400 and 800mg/kg) showed significant protection compared to control group, and MeCO was more potent than AeCO. Based on these outcomes, only MeCO was evaluated in MES and PTZ models. Notably, the MeCO (25, 50, 100 and 200mg/kg) has offered significant and dose- dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeCO (100 and 200mg/kg) showed a significant increase in GABA levels in the brain compared to control. In line with these findings, the anti-PTZ effect of MeCO (100mg/kg, p.o.) was blocked when co-administered with flumazenil (3mg/kg, i.p.),and in NMDA-induced mortality test, the MeCO has shown only 50% protection at 200mg/kg dose, thus confirmed the significant role of GABA pathway. Interestingly, the MeCO did not cause significant change in locomotor activity compared to before treatment. CONCLUSION: These findings suggest that MeCO possess significant anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanisms behind the anticonvulsant activity of MeCO.

Achyranthes aspera Attenuates epilepsy in experimental animals: possible involvement of GABAergic mechanism.

The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA.

Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice.

OBJECTIVES: This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. MATERIALS AND METHODS: Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. RESULTS: In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels (P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. CONCLUSION: These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain.