, Bangalore, India.
Shadan College of Pharmacy. (SCOP) Peerancheru, Hyderabad, 500086, India.
Neurotox Res. 2020 Dec;38(4):1010-1023. doi: 10.1007/s12640-020-00267-0. Epub 2020 Aug 17.
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 GABA 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.
本研究旨在评估毛蕊花糖苷的抗惊厥活性，并探讨其作用机制。首先，在最大电休克（MES）和戊四氮（PTZ）诱导的惊厥模型中评价毛蕊花糖苷的作用，然后在瑞士白化小鼠中评价其对 N-甲基-D-天冬氨酸（NMDA）诱导的死亡率的作用。基于这些模型中的反应，进一步进行评估以探讨作用机制。结果显示，毛蕊花糖苷（10、25 和 50mg/kg）在 PTZ 模型中表现出显著的抗惊厥活性（所有剂量均 p<0.01）；然而，在 MES 和 NMDA 模型中未观察到保护作用。因此，在 PTZ 模型中进行了进一步的基于机制的研究，结果表明，PTZ 处理动物的皮质和海马区中 GABA（p<0.01 用于两个区域）显著减少，谷氨酸显著增加（p<0.01 用于两个区域）。此外，抗氧化剂水平（SOD、过氧化氢酶、GPx、GR、GSH、LPO）发生显著变化（所有参数均 p<0.01），与正常对照组相比，PTZ 对照组的 GABA mRNA 水平降低（p<0.01）。有趣的是，与 PTZ 对照组相比，毛蕊花糖苷（25mg/kg）（所有参数均 p<0.01）的共给药恢复了所有由 PTZ 诱导的变化。此外，在氟马西尼存在下，毛蕊花糖苷的抗 PTZ 作用完全被阻断，从而证实了毛蕊花糖苷抗惊厥活性背后的 GABA 能机制。此外，actophotometer 和转棒试验证实毛蕊花糖苷无中枢副作用，如运动不协调和运动缺陷。
