Chitkara School of Pharmacy, Chitkara University, Solan, Himachal Pradesh, India.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
Neurochem Res. 2024 Jan;49(1):52-65. doi: 10.1007/s11064-023-04009-4. Epub 2023 Aug 19.
Increased oxidative stress and acetylcholinesterase (AChE) activity are key pathological characters contributing to the memory disorders. Thus, drugs targeting both oxidative stress and AChE are being explored for the management of cognitive dysfunction. Morus alba fruits (commonly consumed for its high nutritious value) are known to have antioxidant and AChE inhibitory effects. However, the role of Morus alba fruits in the management of memory disorders has not reported yet. This investigation was conducted to assess the antioxidant and AChE inhibitory potential of Morus alba fruit extracts in-vitro and to identify the components responsible for such effects. Further, the obtained bioactive component was studied for possible memory improvement effects against streptozotocin (STZ) induced dementia. To isolate the bioactive component in-vitro DPPH and AChE assays guided fractionation was performed. Memory functions in mice were determined using Morris Water Maze test while brain biochemical parameters were measured to understand the mechanism of action. In-vitro assays revealed strong AChE and DPPH inhibitory potential of methanol extract (ME), therefore, it was further fractionated. Among various fractions obtained, ethyl-acetate fraction (EAF) was found to possess marked AChE and DPPH inhibitory activities. On subsequent fractionation of EAF, bioactivity of obtained sub-fractions was found to be inferior to EAF. Further, both ME and EAF improved STZ (intracerebroventricular) induced cognitive dysfunction in animals by restoring endogenous antioxidant status (superoxide dismutase and reduced glutathione) and reducing thiobarbituric acid reactive species and nitric oxide levels along with brain AChE and myeloperoxidase activity. TLC densitometric studies showed appreciable levels of phenolic acids and quercetin in both EAF and ME. It can be concluded that Morus alba fruit extract has the ability to modulate cholinergic and oxidative system due to presence of phenolic and flavonoid compounds and hence, could aid in the management of memory disorders.
氧化应激和乙酰胆碱酯酶(AChE)活性的增加是导致记忆障碍的关键病理特征。因此,针对氧化应激和 AChE 的药物正被探索用于认知功能障碍的管理。桑椹(因其高营养价值而被广泛食用)具有抗氧化和 AChE 抑制作用。然而,桑椹在记忆障碍管理中的作用尚未报道。本研究旨在评估桑椹提取物的体外抗氧化和 AChE 抑制潜力,并确定负责这种作用的成分。此外,还研究了获得的生物活性成分对链脲佐菌素(STZ)诱导的痴呆的可能改善记忆作用。为了在体外分离生物活性成分,进行了 DPPH 和 AChE 测定指导的分级分离。使用 Morris 水迷宫测试来确定小鼠的记忆功能,同时测量大脑生化参数以了解作用机制。体外测定显示甲醇提取物(ME)具有很强的 AChE 和 DPPH 抑制潜力,因此进一步进行了分级分离。在获得的各种馏分中,发现乙基-乙酸乙酯馏分(EAF)具有显著的 AChE 和 DPPH 抑制活性。在随后对 EAF 的分级分离中,获得的亚馏分的生物活性发现不如 EAF。此外,ME 和 EAF 通过恢复内源性抗氧化状态(超氧化物歧化酶和还原型谷胱甘肽)以及降低硫代巴比妥酸反应性物质和一氧化氮水平,同时降低大脑 AChE 和髓过氧化物酶活性,改善了 STZ(侧脑室)诱导的动物认知功能障碍。TLC 密度测定研究表明,EAF 和 ME 中均含有相当水平的酚酸和槲皮素。可以得出结论,由于存在酚类和类黄酮化合物,桑椹提取物具有调节胆碱能和氧化系统的能力,因此有助于记忆障碍的管理。