Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system

Abstract

Abstract Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague‒Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1β, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1β/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.