Sarangi Sudhir Chandra, Pattnaik Soumya Sucharita, Joshi Dipesh, Chandra P Prarthana, Kaleekal Thomas
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Center of Excellence Epilepsy, All India Institute of Medical Sciences, New Delhi, India.
Saudi Pharm J. 2020 Nov;28(11):1440-1450. doi: 10.1016/j.jsps.2020.09.010. Epub 2020 Sep 21.
This study assessed adjuvant potential of hydroalcoholic extract (OSHE) with antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT) in maximal electroshock seizure (MES) model in male Wistar rats.
Pharmacodynamic effect of OSHE (1000 mg/kg) was assessed through seizure protection potential, neurobehavioral tests and oxidative stress estimation in MES model after 14 days administration of OSHE alone or combination with maximal (M) and sub-maximal (SM) dose of CBZ or PHT. Pharmacokinetic interaction of OSHE with AEDs was also assessed after 14 days of drug treatment.
OSHE showed 50% protection against MES-induced seizures. Combination of OSHE with AEDs' SM dose enhanced its seizure protection potential. Significant reduction in duration of tonic hind limb extension was observed in CBZ-SM + OSHE as compared to control group (p = 0.006). Among neurobehavioral tests in Morris water maze test rats of CBZ-M + OSHE took significantly less time to reach the platform (p = 0.022) and spent more time in target quadrant (p = 0.016) as compared to other groups. Similarly, rats of PHT-SM + OSHE group spent significantly more time in the target quadrant (p = 0.013). In elevated plus maze test, CBZ-M + OSHE had significantly decreased transfer latency compared to other groups (p = 0.013). OSHE alone treated group had significantly lower oxidative stress as compared to other groups. No significant pharmacokinetic interaction was observed between OSHE and AEDs (CBZ, PHT).
Ocimum's potential of enhanced seizure protection and neuroprotection along with minimal drug interaction with AEDs substantiate its adjuvant role in the management of epilepsy.
本研究在雄性Wistar大鼠的最大电休克惊厥（MES）模型中评估了水醇提取物（OSHE）与抗癫痫药物（AEDs）卡马西平（CBZ）和苯妥英（PHT）联用的辅助潜力。
单独给予OSHE（1000 mg/kg）或与最大（M）和次最大（SM）剂量的CBZ或PHT联合给药14天后，通过MES模型中的惊厥保护潜力、神经行为测试和氧化应激评估来测定OSHE的药效学作用。药物治疗14天后还评估了OSHE与AEDs的药代动力学相互作用。
OSHE对MES诱导的惊厥显示出50%的保护作用。OSHE与AEDs的SM剂量联合使用可增强其惊厥保护潜力。与对照组相比，CBZ-SM + OSHE组的强直性后肢伸展持续时间显著缩短（p = 0.006）。在Morris水迷宫测试的神经行为测试中，与其他组相比，CBZ-M + OSHE组的大鼠到达平台的时间显著缩短（p = 0.022），并且在目标象限花费的时间更多（p = 0.016）。同样，PHT-SM + OSHE组的大鼠在目标象限花费的时间显著更多（p = 0.013）。在高架十字迷宫测试中，与其他组相比，CBZ-M + OSHE组的转换潜伏期显著缩短（p = 0.013）。与其他组相比，单独使用OSHE治疗的组氧化应激显著更低。未观察到OSHE与AEDs（CBZ、PHT）之间有显著的药代动力学相互作用。
罗勒增强惊厥保护和神经保护的潜力以及与AEDs的药物相互作用最小，证实了其在癫痫治疗中的辅助作用。
