Department of Research and Development, Saveetha University, Chennai, 602 105, India.
Department of Neurology, University of Medicine Rostock, Rostock, Germany.
J Chem Neuroanat. 2018 Dec;94:75-85. doi: 10.1016/j.jchemneu.2018.09.002. Epub 2018 Sep 29.
Ischemic brain injury is one of the leading causes of death and disability, where lack of disease modifying treatment strategies make us rely on symptomatic relief. Treatment principles from traditional systems of medicine may fill this gap and its validation in modern medicine perspective is important to bring them to mainstream. Here, we evaluated the neuroprotective efficacy of Ayurvedic medicinal herb Pluchea lanceolata in treating ischemic hippocampal injury. Focal hippocampal ischemia was modeled in Wistar rats through stereotaxic intrahippocampal injection of endothelin-1 (ET-1). Post-surgery, hydroalcoholic extract of the rhizome of Pluchea lanceolata (HAPL) was administered orally, once in a day for 14 consecutive days to ischemic rats. There were two treatment groups based on the HAPL dosage; HAPL200 (200 mg/kg body weight) and HAPL400 (400 mg/kg body weight). Comparisons were made with the ET-1 ischemic rats which received only the vehicle, and the normal surgical control. Ischemic hippocampal injury led to severe cognitive deficits as evaluated by Morris water maze and open field test, along with locomotory dysfunction noted in actophotometer test. HAPL treatment significantly attenuated these behavioural deficits in a dose dependent manner. Loss of pyramidal cells and degenerative phenotype of shrunken hyperdensed soma with pyknotic nuclei in CA1 and CA3 hippocampal neurons in ischemia were reversed after HAPL treatment. We provide first evidence for loss of dendritic architecture in ET-1 induced focal ischemic hippocampal injury using Golgi impregnation, where HAPL could salvage the dendritic branching and intersections. Intriguingly, it enhanced the dentritic arborization beyond what is noted in normal rats. Ability of HAPL to reverse oxidative stress, especially through maintaining glutathione peroxidase levels and lipid peroxidation in ischemic condition evidences that it may exert neuroprotection through its antioxidant properties. Thus, Pluchea lanceolata and its constituents provide potential alternative/adjuvant treatment strategy for ischemic hippocampal stroke.
缺血性脑损伤是导致死亡和残疾的主要原因之一，由于缺乏疾病修饰治疗策略，我们只能依赖对症缓解。传统医学体系的治疗原则可能会填补这一空白，将其在现代医学视角下进行验证对于将其引入主流至关重要。在这里，我们评估了印度草药 Pluchea lanceolata 在治疗缺血性海马损伤中的神经保护作用。通过立体定向海马内注射内皮素-1 (ET-1) 在 Wistar 大鼠中建立局灶性海马缺血模型。手术后，通过口服给予 Pluchea lanceolata 根茎的水醇提取物（HAPL），每天一次，连续 14 天给予缺血大鼠。根据 HAPL 剂量，有两个治疗组；HAPL200（200mg/kg 体重）和 HAPL400（400mg/kg 体重）。与仅接受载体的 ET-1 缺血大鼠和正常手术对照组进行比较。水迷宫和旷场试验评估缺血性海马损伤导致严重的认知缺陷，并且在活动光度计试验中观察到运动功能障碍。HAPL 治疗以剂量依赖的方式显著减轻这些行为缺陷。HAPL 治疗后，CA1 和 CA3 海马神经元中缺血引起的锥体神经元丢失和皱缩超密体的退行性表型（核固缩）得到逆转。我们首次使用高尔基染色提供了 ET-1 诱导的局灶性缺血性海马损伤中树突结构丢失的证据，其中 HAPL 可以挽救树突分支和交点。有趣的是，它增强了树突分支超过正常大鼠的分支。HAPL 逆转氧化应激的能力，特别是通过维持缺血状态下谷胱甘肽过氧化物酶水平和脂质过氧化作用，证明它可能通过其抗氧化特性发挥神经保护作用。因此，Pluchea lanceolata 及其成分可能为缺血性海马卒中提供潜在的替代/辅助治疗策略。
