Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Tamil Nadu, 608002, India.
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, Karnataka, 570015, India.
Neurotox Res. 2019 May;35(4):955-968. doi: 10.1007/s12640-019-9999-2. Epub 2019 Jan 22.
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 (AlCl)-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/GSK3β signaling pathway on AlCl-induced neurotoxicity in Wistar rats. AD-like pathology was induced by oral administration of AlCl (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/GSK3β pathway. Current results suggested that AA could be able to modulate various pathological features of AD and could hold promise in AD treatment.
积雪草酸（AA）是一种存在于积雪草中的三萜类化合物，具有穿过血脑屏障的能力，因其具有神经保护作用而受到广泛关注。我们已经报道了 AA 对氯化铝（AlCl）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）样模型大鼠炎症的益处。基于此，为了找到 AA 的确切作用机制，本研究旨在评估氧化应激、tau 病理、细胞凋亡和 Akt/GSK3β 信号通路对 Wistar 大鼠 AlCl 诱导的神经毒性的影响。通过口服 AlCl（100mg/kg b.w.）6 周诱导 AD 样病理学，结果表明空间记忆性能、焦虑和运动功能障碍显著降低，周期蛋白依赖性激酶 5（CDK5-参与 tau 蛋白磷酸化的酶）、pTau、氧化应激和细胞凋亡的表达减少，而口服 AA（75mg/kg b.w.）7 周可减轻上述指标，这可能是通过激活 Akt/GSK3β 通路实现的。目前的结果表明，AA 可能能够调节 AD 的各种病理特征，并有望用于 AD 的治疗。
