Shakeel Sheeba, Rehman Muneeb U, Tabassum Nahida, Amin Umar, Mir Manzoor Ur Rahman
Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar, Jammu and Kashmir, India.
Molecular Biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Sheri Kashmir University of Agricultural Science and Technology-Kashmir (SKUAST-K), Srinagar, Jammu and Kashmir, India.
Pharmacogn Mag. 2017 Jan;13(Suppl 1):S154-S160. doi: 10.4103/0973-1296.203977. Epub 2017 Apr 7.
Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favourably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the effects of naringenin in pilocarpine-induced epilepsy in mice. Naringenin, one of the most frequently occurring flavanone in citrus fruits, was evaluated for its shielding effect against the pilocarpine induced behavioural, oxidative and histopathological alterations in rodent model of epilepsy.
Epilepsy was induced by giving pilocarpine (300mg/kg) and sodium valproate (300mg/kg) was given as standard anti-epileptic drug Pilocarpine was administered (300 mg /kg body weight) intraperitoneally to the mice on 15th day while naringenin was administered orally (20 and 40 mg/kg body weight) for 15 days prior to administration of pilocarpine.
The intraperitoneal administration of pilocarpine enhanced lipid peroxidation, caused reduction in antioxidant enzymes, viz., catalase, superoxide dismutase and glutathione reductase. Treatment of mice orally with naringenin (20 mg/kg body weight and 40 mg/kg body weight) resulted in a significant decrease in lipid peroxidation. There was significant recovery of glutathione content and all the antioxidant enzymes studied. Also in case of behavioural parameters studied, naringenin showed decrease in seizure severity. All these changes were supported by histological observations, which revealed excellent improvement in neuronal damage.
The higher dose of naringenin was more potent in our study and was comparable to the standard drug (sodium valproate) in effectiveness.
Naringenin ameliorated the development of ROS formation in hippocamus.Naringenin helped in recovery of antioxidant enzymes.Naringenin decreased seizure severity.Naringenin treatment reduced lipid peroxidation. 6-OHDA: 6-hydroxydopamine, AED: Anti epileptic drugs, AIDS: Acquired immune deficiency syndrome, ANOVA: Analysis of variance, ATP: Adenosine triphosphate, CA: Cornu ammonis, CAT: Catalase, DG: Dentate gyrus, EDTA: Ethylenediamine tetra acetic acid, GR: Glutathione reductase, GSH: Glutathione reduced, HCl: Hydrochloric acid, IL-1β: Interleukin 1 beta, LPO: Lipid peroxidation, MDA: Malondialdehyde, NADPH: Nicotinamide adenine dinucleotide phosphate, PMS: post mitochondrial supernatant, SE: Status epilepticus, SEM: Standard error of the mean, SOD Superoxide dismutase, TBA: Thiobarbituric acid, TBARS: Thiobarbituric acid reactive substance, TLE: Temporal lobe epilepsy, TNF-α: Tumor necrosis factor alpha.
癫痫是一种中枢神经系统疾病,其特征为反复发作的癫痫发作。它是一种非常常见的疾病,约30%的患者对抗惊厥药物治疗反应不佳。氧化应激与癫痫发作引起的神经元损伤有关。本研究调查了柚皮素对毛果芸香碱诱导的小鼠癫痫的影响。柚皮素是柑橘类水果中最常见的黄酮之一,评估了其对癫痫啮齿动物模型中毛果芸香碱诱导的行为、氧化和组织病理学改变的保护作用。
通过给予毛果芸香碱(300mg/kg)诱导癫痫,丙戊酸钠(300mg/kg)作为标准抗癫痫药物。在第15天给小鼠腹腔注射毛果芸香碱(300mg/kg体重),而在注射毛果芸香碱前15天给小鼠口服柚皮素(20mg/kg和40mg/kg体重)。
腹腔注射毛果芸香碱增强了脂质过氧化,导致抗氧化酶(即过氧化氢酶、超氧化物歧化酶和谷胱甘肽还原酶)减少。用柚皮素(20mg/kg体重和40mg/kg体重)口服治疗小鼠导致脂质过氧化显著降低。谷胱甘肽含量和所有研究的抗氧化酶有显著恢复。在研究的行为参数方面,柚皮素也显示癫痫严重程度降低。所有这些变化都得到了组织学观察的支持,组织学观察显示神经元损伤有明显改善。
在我们的研究中,较高剂量的柚皮素更有效,并且在有效性上与标准药物(丙戊酸钠)相当。
柚皮素改善了海马体中活性氧形成的发展。柚皮素有助于抗氧化酶的恢复。柚皮素降低癫痫严重程度。柚皮素治疗减少脂质过氧化。6-OHDA:6-羟基多巴胺,AED:抗癫痫药物,AIDS:获得性免疫缺陷综合征,ANOVA:方差分析,ATP:三磷酸腺苷,CA:海马,CAT:过氧化氢酶;DG:齿状回,EDTA:乙二胺四乙酸,GR:谷胱甘肽还原酶,GSH:还原型谷胱甘肽,HCl:盐酸,IL-1β:白细胞介素1β,LPO:脂质过氧化,MDA:丙二醛,NADPH:烟酰胺腺嘌呤二核苷酸磷酸,PMS:线粒体后上清液,SE:癫痫持续状态,SEM:均值标准误差,SOD:超氧化物歧化酶,TBA:硫代巴比妥酸,TBARS:硫代巴比妥酸反应性物质,TLE:颞叶癫痫,TNF-α:肿瘤坏死因子α。