rohit kumar
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Introduction
Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model.
MethodsPTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mgkg, pergolide 2 mg/kg, C. paniculatus (250 mgkg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mgkg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed.
ResultsC. paniculatus (500 mg/kg) alone and in combination ( C. paniculatus (250 mgkg)+ pergolide (1 mg/kg) and C. paniculatus (250 mgkg)+ SVA (100 mg/kg)) significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in the MWM. However, no significant effect was seen in GPS. Biochemical analysis showed elevated antioxidant markers, namely GSH, CAT, and SOD, and also elevated dopamine levels. C. paniculatus and its combination also significantly (P<0.05) protected against neuronal loss in the hippocampus and frontal cortex evidenced by H&E staining
ConclusionC. paniculatus alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits
Keywords: C. paniculatus, Hippocampus, Kindling, Oxidative stress, Pentylenetetrazole -
Currently available disease modifying anti-rheumatoid drugs have limitations like dose-dependent toxicity and tolerance.Dimethyl fumarate has demonstrated anti-inflammatory and immunomodulatory properties in various animal models. Thus, thepresent study aimed to evaluate the effects and mechanism of DMF in a murine model of adjuvant-induced arthritis.A total of 84 rats were divided into early treatment groups (n=48) and late treatment groups (n=36). There were 8 subgroupsand 6 subgroups (n=6 in each group) in the early and late treatment groups, respectively. Experimental rheumatoid arthritis(RA) was induced in Wistar rats by injecting complete Freund's adjuvant (CFA) intradermally at the base of the tail. Antirheumatic effects were evaluated by arthritis and histopathological scoring of ankle joints. To evaluate anti-oxidant properties,GSH, catalase, SOD, and lipid peroxidation were measured. ESR, WBC count, TNF-α and IL-6 levels were measured to evaluatethe immunomodulatory properties of DMF. DMF demonstrated anti-inflammatory effects by decreasing arthritis andhistopathological scores compared to the CFA control group, though the difference was not statistically significant. DMFexhibited immunomodulatory properties as decreases in TLC count, serum TNF-α, and plasma IL-6 levels were observed. In allthe above-mentioned parameters, the best response was achieved with the early combination therapy of DMF 30 mg/kg andmethotrexate [Mtx] 0.1 mg/kg. In the present study, DMF demonstrated antirheumatoid effects in a rat model of CFA-inducedarthritis. The best antirheumatoid effect was achieved with the early combination of DMF and Mtx.
Keywords: anti-inflammatory agents, Antioxidants arthritis, Dimethyl fumarate, Freund's adjuvant, Rheumatoid
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