School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan; Department of Psychiatry, Cathay General Hospital, Taipei 106438, Taiwan.
Int Immunopharmacol. 2024 Oct 25;140:112842. doi: 10.1016/j.intimp.2024.112842. Epub 2024 Aug 1.
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.
台湾清冠一号（NRICM101）是一种用于治疗 2019 年冠状病毒病的中药方剂，但它对癫痫的影响尚未被揭示。因此，本研究评估了口服 NRICM101 对大鼠海人酸（KA）诱导的癫痫发作的抗癫痫作用，并探讨了其可能的作用机制。SD 大鼠连续 7 天经口灌胃 NRICM101（300mg/kg），然后腹腔注射 KA（15mg/kg）。NRICM101 可显著减轻 KA 诱导的大鼠癫痫发作行为和脑电图癫痫发作。NRICM101 还可显著减少神经元丢失和谷氨酸增加，并增加 KA 处理大鼠皮质和海马中的 GLAST、GLT-1、GAD67、GDH 和 GS 水平。此外，NRICM101 可显著抑制星形胶质细胞增生（由 GFAP 表达减少确定）；神经炎症信号（由 HMGB1、TLR-4、IL-1β、IL-1R、IL-6、p-JAK2、p-STAT3、TNF-α、TNFR1 和 p-IκB 水平降低和胞质 p65-NFκB 水平升高确定）；以及 KA 处理大鼠皮质和海马中的坏死性凋亡（由 p-RIPK3 和 p-MLKL 水平降低确定）。NRICM101 的作用与卡马西平相似，卡马西平是一种公认的抗癫痫药物。此外，在 NRICM101 处理的大鼠中未观察到 NRICM101 对肝脏和肾脏的毒性作用。结果表明，NRICM101 通过抑制与谷氨酸水平调节相关的炎症线索（HMGB1/TLR4、IL-1β/IL-1R1、IL-6/p-JAK2/p-STAT3 和 TNF-α/TNFR1/NF-κB）和坏死性凋亡信号通路（TNF-α/TNFR1/RIP3/MLKL），具有抗癫痫和神经保护作用，且无毒。我们的研究结果强调了 NRICM101 在癫痫管理中的有前途的作用。
