Neuroprotective Effect of Otostegia limbata Against PTZ-Induced Mice Model of Epilepsy by Attenuated Expression of p-NFκB and TNF-α

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures. Currently available antiepileptic drugs have severe side effects and do not offer complete cure. Herbal remedies have been used for centuries to treat many neurodegenerative disorders. Otostegia limbata L. belongs to the largest and medicinally important family Lamiaceae and is distributed in hilly areas of Pakistan. This study was designed to assess the antioxidant, anti-inflammatory, and anticonvulsant potential of O. limbata. The methanolic extract showed significant antioxidant activity assessed by (1,1-diphenyl 2-picrylhydrazyl) free-radical scavenging assay, nitric oxide scavenging, and iron chelation antioxidant assays. The methanolic extract was evaluated for its anticonvulsant effect, employing the pentylenetetrazole (PTZ)-induced mice model of epilepsy. Three different doses of O. limbata (100, 200, and 300 mg/kg) were administered orally 30 min before PTZ [50 mg/kg, intraperitoneal (i.p.)] injection, while diazepam was used as a positive control. The extract at 300 mg/kg significantly decreased the duration and increased the latency of the PTZ-induced seizures. The expression of inflammatory cytokines tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB), in the cortex and hippocampus of the brains of treated mice were analyzed through enzyme-linked immunosorbent assay and western blot analysis. The morphological changes and number of surviving neurons were recorded through hematoxylin and eosin staining. The seizure score and survival rate of the treated group showed considerable differences as compared to the PTZ group. TNF-α and p-NF-K b expression were downregulated as compared to the PTZ group. The anticonvulsant effect may be the outcome of the antioxidant potential and high levels of phenols and flavonoids detected in the methanolic plant extract through Fourier transform infrared spectrophotometer and gas chromatography–mass spectrometry analysis.

An investigation of the phytochemical richness of fresh Musa paradisiaca L. (plantain) stem juice and its anticonvulsant potential on pentylenetetrazole (PTZ)-challenged rats

“…The result of this nding corresponds with the work of Al-Sna (2015) which reported a delay of clonic convulsion onset in experimental rodents at low doses of chloroform and aqueous extracts of Calotropis procera. It also agreed with the increased latency of PTZ-induced clonic convulsions in albino mice observed after oral doses of Otostegia limbata L extracts (Amin et al, 2022). The observations of this result suggest that the fresh MP stem juice has a particular active compound (s) that confers on it, the ability to delay the onset of clonic seizure.…”

Analysis of the action mechanisms and targets of herbal anticonvulsants highlights opportunities for therapeutic engagement with refractory epilepsy

“…In the same model, the extracts of Artemisia increased the antioxidant capacity of the serum and brain tissue. These favorable outcomes correlate with the reduced frequency of spinning and jumping of epileptic mice [56] and the attenuation of their tonic seizures. Interestingly, the anticonvulsant effects of A. persica extracts can be enhanced by diazepam, while flumazenil has the opposite effect.…”

“…A recent analysis of the effects of methanolic extracts of Otostegia limbata on the expression of TNF-α and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) in the cortex and hippocampus of the PTZ-induced convulsion model showed significant anti-inflammatory effects associated with shorter duration and increased latency of seizures [ 56 ] (Fig. 2 , Table 1 ).…”

Sinapic Acid Mitigates Pentylenetetrazol-induced Acute Seizures By Modulating the NLRP3 Inflammasome and Regulating Calcium/calcineurin Signaling: In Vivo and In Silico Approaches

“…Notably, a blinded technician applied random animal distribution. A total of 48 mice were randomly divided into six groups (8 mice/group) as Group 1 (Normal control group); mice were injected with 1 ml/kg single dose of IP physiological saline, Group 2 (Acute seizure model; PTZ group); mice were injected with single dose of IP PTZ (50 mg/kg) [53], Group 3 (SA (20 mg) group) [54]; animals were given daily doses of oral SA solution (20 mg/kg) for 21 days, Group 4 (SA (20 mg) + PTZ group); mice were given daily oral doses of SA solution (20 mg/kg) for 21 days followed by single dose of IP PTZ (50 mg/kg), Group 5 (SA (40 mg) group) [54]; mice were given daily doses of oral SA solution (40 mg/kg) for 21 days and Group 6 (SA (40 mg) + PTZ group); animals were given daily oral doses of SA solution (40 mg/kg) for 21 days followed by single dose of IP PTZ (50 mg/kg). The PTZ-treated mice were then placed individually in a transparent acrylic plastic box to record their seizure behavior before being euthanized via cervical dislocation.…”