Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats.
Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats.
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DOI：
10.1016/j.jep.2017.12.008
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发表时间：
2018-04
影响因子：
5.4
通讯作者：
Ritesh Kumar;R. Arora;A. Agarwal;Y. Gupta
中科院分区：
文献类型：
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作者：
Ritesh Kumar;R. Arora;A. Agarwal;Y. Gupta
Teminalia chebula（TC）传统上用于阿育吠陀医学系统，主要用于胃肠道疾病。其果实提取物也被用于治疗癫痫和其他CNS disorders.Aim的studyTo评估的效果，水乙醇水果提取物的诃子（HETC）对癫痫发作，癫痫引起的认知障碍和氧化应激rats.Materials和方法模型HETC体外抗氧化活性进行了评估，通过使用ABTS，NO和DPPH自由基清除试验。在体研究中，用戊四氮（PTZ）和最大电休克诱发Wistar大鼠（200-225 g）癫痫发作。（MES）。在癫痫发作模型中评价了HETC（250、500和1000 mg/kg，经口）的抗惊厥作用。还测定了丙戊酸盐和苯妥英的治疗剂量和亚治疗剂量。还分别在PTZ和MES癫痫发作模型中评价了HETC（500 mg/kg）与亚治疗剂量丙戊酸盐和苯妥英联合给药的潜在影响。使用高架十字迷宫（ESTA）和被动回避试验（PA）评估对认知的影响。结果HETC对ABTS、DPPH和NO自由基清除的IC_（50）分别为2.27 μg/ml、6.04 μg/ml和4.37 μg/ml;在实验研究中，与对照组相比，PTZ和MES治疗组表现出100%的癫痫发作，氧化应激（p < 0.001）和认知缺陷（p < 0.01）增加。HETC最高剂量（1000 mg/kg）对MES诱导的癫痫发作有83.33%（5/6）的保护作用，对PTZ诱导的癫痫发作有66.66%（4/6）的保护作用。然而，HETC（1000 mg/kg）和亚治疗剂量HETC与丙戊酸盐和苯妥英联合给药显示出完全保护作用。此外，本发明还提供了一种方法，它还减弱了癫痫引起的氧化应激和认知障碍，（p < 0.01），但不影响正常人的生活。与PTZ和MES治疗组相比，HETC和PA中的转运延迟改善。结论研究结果表明，HETC具有显著的抗惊厥活性，并且还增强了苯妥英钠和丙戊酸盐的亚治疗剂量，表明其作为抗癫痫药物的辅助治疗的有用性，预防认知障碍和氧化应激的优势。
Ethnopharmacological relevanceTeminalia chebula(TC) has been traditionally used in the Ayurvedic system of medicine primarily for gastrointestinal disorders. Its fruit extract has also been used to treat epilepsy and other CNS disorders.Aim of the studyTo evaluate the effect of hydroalcoholic fruit extract ofTerminalia chebula(HETC) on experimental models of seizures, seizure-induced cognitive impairment and oxidative stress in rats.Materials and methodsIn vitroantioxidant activity of HETC was evaluated by using ABTS, NO and DPPH radical scavenging assay. Forin-vivostudy, seizures were induced in Wistar rats (200–225 g) by pentylenetetrazole (PTZ) and maximal-electroshock. (MES). The anticonvulsant effect of the HETC (250, 500, and 1000 mg/kg, orally) was evaluated in seizure models. The therapeutic and sub-therapeutic dose of valproate and phenytoin were also assayed. The potential effect of co-administration of HETC (500 mg/kg) with sub-therapeutic dose of valproate and phenytoin were also evaluated in PTZ and MES seizures model respectively. Effect on cognition was assessed using elevated plus maze (EPM) and passive avoidance test (PA). Thein- vivooxidative stress parameters (malondialdehyde and glutathione) were assessed in the cerebral cortex and hippocampus part of rat brain.ResultsThe IC50 value of HETC inin vitroantioxidant assaysi.e.ABTS, DPPH and NO radical scavenging assay was found to be 2.27 μg/ml, 6.04 μg/ml and 4.37 μg/ml respectively. In experimental study, PTZ and MES treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000 mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000 mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in EPM and PA as compared to PTZ and MES treated group.ConclusionsThe findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.