STZ is a glucosamine-nitrosourea compound, causes dysfunctioning of insulin receptors in the brain and disrupts glucose metabolism, produces cognitive decline and AD-like symptoms. ICV injection of STZ causes accumulation of Aβ and cognitive dysfunctions. Andrographolide (ANDRO) is a major bioactive constituent of Andrographis paniculata, has various biological activities such as antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties. The study aimed to evaluate the neuroprotective effect of ANDRO against ICV-STZ induced AD-like symptoms in rats. To conduct the study, the Wistar rat received two injections of STZ (3 mg/kg) through the ICV route. Rats were treated with three different doses of ANDRO (15, 30, and 60 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 14 days. The behavioral impairments were analyzed on weekly basis. Subsequently, rats were sacrificed for the assessment of biochemical (MDA, Nitrite, GSH, SOD, Catalase and AChE), neuroinflammatory markers (IL-1β, IL-16, and TNF-α), neurotransmitters (glutamate and GABA), level of Aβ_1–42 and p tau in the hippocampus on day 21st. Our result indicated that ANDRO treatment provided a protective effect against STZ induced behavioral deficits and changes in the biochemical, neuroinflammatory mediators, and neurotransmitters of the hippocampus. Further, ANDRO also reduced the level of Aβ_1–42 and p tau in the rat hippocampus. These findings suggested that the antioxidant, anti-inflammatory, anti-cholinesterase potential of ANDRO contributed to its neuroprotective effect as well as promising therapeutic candidate for the treatment of cognitive impairment and AD-like symptoms.

STZ 是一种氨基葡萄糖-亚硝基脲化合物，会导致大脑中胰岛素受体功能障碍并扰乱葡萄糖代谢，导致认知能力下降和 AD 样症状。ICV 注射 STZ 导致 Aβ 积累和认知功能障碍。穿心莲内酯 (ANDRO) 是穿心莲的主要生物活性成分, 具有抗氧化、抗炎、抗胆碱酯酶和神经保护等多种生物活性。该研究旨在评估 ANDRO 对 ICV-STZ 诱导的大鼠 AD 样症状的神经保护作用。为了进行这项研究，Wistar 大鼠通过 ICV 途径接受了两次 STZ (3 mg/kg) 注射。大鼠用三种不同剂量的 ANDRO（15、30 和 60 mg/kg，po）和多奈哌齐（5 mg/kg，po）处理 14 天。每周分析行为障碍。随后，处死大鼠以评估生化指标（MDA、亚硝酸盐、GSH、SOD、过氧化氢酶和 AChE）、神经炎症标志物（IL-1β、IL-16 和 TNF-α）、神经递质（谷氨酸和 GABA）、 Aβ _1–42和p第 21 天海马体中的 tau 蛋白。我们的结果表明，ANDRO 治疗对 STZ 诱导的行为缺陷和海马体生化、神经炎症介质和神经递质的变化具有保护作用。此外，ANDRO 还降低了大鼠海马体中Aβ _1-42和ptau的水平。这些发现表明 ANDRO 的抗氧化、抗炎、抗胆碱酯酶潜力有助于其神经保护作用以及治疗认知障碍和 AD 样症状的有前途的治疗候选药物。