Hussein Rehab A, Afifi Ahmed H, Soliman Ahmed A F, El Shahid Zeinab A, Zoheir Khairy M A, Mahmoud Khaled M
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, PO 12622, 33 El Bohouth St. (Former El Tahrir St.), Dokki, Giza, Egypt.
Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, PO 12622, 33 El Bohouth St. (Former El Tahrir St.), Dokki, Giza, Egypt.
Heliyon. 2020 Dec 14;6(12):e05678. doi: 10.1016/j.heliyon.2020.e05678. eCollection 2020 Dec.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders which affects the hippocampus and cortical neurons leading to impairment of cognitive ability. Treatment of AD depends mainly on acetylcholinesterase inhibitors, however, a novel therapeutic approach is introduced based on the maintenance of neuronal viability and functionality exerted through neurotrophic factors. In the current study, L. leaves alcoholic extract was investigated for its neuroprotective activity in AlCl-induced AD in rats. Rats were orally treated with AlCl (17 mg/kg) for 4 weeks followed by extract (150 mg/kg b.wt.) for another 6 weeks. Treatment of neuro-intoxicated rats with extract resulted in a significant regulation in neurotrophic factors; brain derived neurotrophic factor and transforming growth factor-β and pro-inflammatory cytokine; TNF. It also induced an elevation in serum levels of monoamine neurotransmitters; norepinephrine, dopamine and serotonin and a decline in brain acetlycholinesterase activity. extract also showed potent antioxidant activity as indicated by the declined malondialdehyde and elevated reduced glutathione, catalase and super oxide dismutase levels in AD rats' brains. Histological improvement was detected in the cerebral cortex, the hippocampus and striatum of the treated rats The phytochemical analysis of extract revealed high contents of flavonoids and phenolics and the major compounds were isolated and chemically characterized. Additionally, extract and the isolated compounds exerted a prominent activity in acetylcholinesterase inhibition assay with kaempferol-3-O-β-glucoside being the most potent compound showing IC of 29.03 ± 0.0155 μM. A molecular docking study indicated high affinity of kaempferol-3-O-β-robinobioside on acetylcholine esterase binding site with estimated binding free energy of -8.26 kcal/mol.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，它会影响海马体和皮质神经元，导致认知能力受损。AD的治疗主要依赖于乙酰胆碱酯酶抑制剂，然而，一种基于通过神经营养因子维持神经元活力和功能的新型治疗方法被引入。在当前的研究中，对L. leaves乙醇提取物在氯化铝诱导的大鼠AD模型中的神经保护活性进行了研究。大鼠口服氯化铝（17毫克/千克）4周，随后口服提取物（150毫克/千克体重）另外6周。用提取物治疗神经中毒大鼠导致神经营养因子（脑源性神经营养因子和转化生长因子-β）以及促炎细胞因子（肿瘤坏死因子）有显著调节。它还使血清中单胺类神经递质（去甲肾上腺素、多巴胺和5-羟色胺）水平升高，脑乙酰胆碱酯酶活性下降。提取物在AD大鼠脑中还表现出强大的抗氧化活性，表现为丙二醛水平下降，还原型谷胱甘肽、过氧化氢酶和超氧化物歧化酶水平升高。在治疗大鼠的大脑皮质、海马体和纹状体中检测到组织学改善。提取物的植物化学分析显示黄酮类和酚类含量高，并对主要化合物进行了分离和化学表征。此外，提取物和分离出的化合物在乙酰胆碱酯酶抑制试验中表现出显著活性，其中山奈酚-3-O-β-葡萄糖苷是最有效的化合物，其IC为29.03±0.0155微摩尔。分子对接研究表明山奈酚-3-O-β-刺槐二糖苷对乙酰胆碱酯酶结合位点具有高亲和力，估计结合自由能为-8.26千卡/摩尔。
