Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis Via AKT/GSK-3β Signaling Pathway in Wistar Rats
Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis Via AKT/GSK-3β Signaling Pathway in Wistar Rats
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DOI：
10.1007/s12640-019-9999-2
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发表时间：
2019-05-01
影响因子：
3.7
通讯作者：
Essa, Musthafa Mohamed
中科院分区：
文献类型：
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作者：
Rather, Mashoque Ahmad;Justin-Thenmozhi, Arokiasamy;Essa, Musthafa Mohamed
亚洲积雪草（Centella asiatica， AA）是一种存在于积雪草中的三萜，具有穿越血脑屏障的能力，其神经保护作用受到广泛关注。我们已经报道了AA对氯化铝（AlCl3）诱导的淀粉样蛋白病理、增强乙酰胆碱酯酶（AChE）活性和阿尔茨海默病（AD）模型大鼠炎症的益处。在此基础上，本研究通过氧化应激、tau病理、细胞凋亡、Akt/GSK3 β信号通路对alcl3诱导的Wistar大鼠神经毒性的影响，探讨AA的确切作用机制。口服AlCl3 （100 mg/kg体重）6周可诱导ad样病理，结果显示空间记忆表现、焦虑和运动功能障碍显著降低，细胞周期蛋白依赖性激酶5 （cdk5 -酶，与tau蛋白磷酸化有关）、pTau、氧化应激和细胞凋亡表达降低，而口服AA （75 mg/kg体重）7周可减弱上述指标。这可能是通过激活Akt/GSK3 β途径实现的。目前的研究结果表明，AA可以调节阿尔茨海默病的各种病理特征，并有望在阿尔茨海默病的治疗。
Asiatic acid (AA), a triterpenoid present in Centella asiatica, possesses the ability to cross blood brain barrier and received considerable attention for its neuroprotective role. We have reported the benefit of AA against aluminum chloride (AlCl3)-induced amyloid pathology, enhanced acetylcholine esterase (AChE) activity, and inflammation in Alzheimer's disease (AD) like model rats. Based on that, to find the exact mechanism of action of AA, the present study was designed to evaluate the oxidative stress, tau pathology, apoptosis, and Akt/GSK3 beta signaling pathway on AlCl3-induced neurotoxicity in Wistar rats. AD-like pathology was induced by oral administration of AlCl3 (100 mg/kg b.w.) for 6 weeks, which demonstrated a significant reduction in spatial memory performance, anxiety, and motor dysfunction and diminished the expression of cyclin-dependent kinase 5 (CDK 5-enzyme implicated in the phosphorylation of tau proteins), pTau, oxidative stress, and apoptosis, whereas oral ingestion of AA (75 mg/kg b.w.) for 7 weeks attenuated the above-said indices, which could be by activating Akt/GSK3 beta pathway. Current results suggested that AA could be able to modulate various pathological features of AD and could hold promise in AD treatment.