Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai, 201203, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai, 201203, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117106. doi: 10.1016/j.jep.2023.117106. Epub 2023 Aug 29.
Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported.
The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action.
C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated.
Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-α, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity.
EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.
阿尔茨海默病（AD）是一种进行性发展的神经退行性疾病，主要发生在老年期。记忆障碍是 AD 的重要表现。研究表明，炎症和氧化应激是 AD 发展和进展的重要介质。党参（CR）已有长期食用历史，具有许多有益的健康功效，包括抗衰老、抗氧化和抗炎作用。然而，关于党参对东莨菪碱诱导的健忘症的影响的研究很少有报道。
本研究旨在探讨党参大分子部分（多糖，POL）和小分子部分（富含苯丙素-多炔的精细提取物，EPP）对改善东莨菪碱诱导的记忆障碍的改善作用，并阐明其潜在的作用机制。
C57BL/6 小鼠经灌胃预处理 EPP（0.2、0.4 和 0.6 g/kg）、POL（0.3、0.6 和 0.9 g/kg）和多奈哌齐（5 mg/kg）7 天，然后腹腔注射东莨菪碱（1 mg/kg）诱导记忆障碍。进行 16S rRNA 基因测序、组织病理学、western blot 和生化分析（与胆碱能系统、氧化应激和神经炎症相关的各种生化标志物和蛋白表达），以进一步阐明作用机制。此外，还评估了 POL、EPP 及其主要化合物党参皂苷 I、芦丁、芦丁醇和芦丁因的乙酰胆碱酯酶（AChE）抑制活性。
实验证实，党参的 POL 和 EPP 均可改善东莨菪碱诱导的空间学习记忆障碍。它们都可以通过抑制 AChE 和激活胆碱乙酰转移酶（ChAT）活性来调节胆碱能功能。它们还可以通过增加超氧化物歧化酶和谷胱甘肽过氧化物酶的活性来增强抗氧化防御功能，并通过抑制炎症因子（一氧化氮、TNF-α 和 IL-6）和调节肠道菌群来增强抗炎功能。此外，体外实验表明，四种单体化合物和 EPP（除 POL 外）均表现出抑制 AChE 活性。
党参的 EPP 和 POL 对东莨菪碱诱导的记忆障碍小鼠的学习和记忆过程有有益的影响。党参可能是预防和改善学习记忆的有前途的药物。
