Food Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea.
Department of Food and Nutrition, Institute of Basic Science, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea.
Nutrients. 2024 Oct 31;16(21):3751. doi: 10.3390/nu16213751.
BACKGROUND/OBJECTIVES: Fructus (SCF) is a traditional medicinal herb containing lignans that improves glucose metabolism by mitigating insulin resistance. We aimed to investigate the therapeutic potential and action mechanism of SCF for Alzheimer's disease (AD) using a network pharmacology analysis, followed by experimental validation in an AD rat model.
The biological activities of SCF's bioactive compounds were assessed through a network pharmacology analysis. An AD rat model was generated by infusing amyloid-β peptide (Aβ) (25-35) into the hippocampus to induce Aβ accumulation. The AD rats were fed either 0.5% dextrin (AD-Con) or 0.5% SCF (AD-SCF group) in a high-fat diet for seven weeks. The rats in the normal/control group received an Aβ (35-25) infusion (no Aβ deposition) and were fed a control diet (Normal-C). Aβ deposition, memory function, inflammation, and glucose/lipid metabolism were evaluated.
The network analysis revealed significant intersections between AD-related targets and bioactive SCF compounds, like gomisin A, schisandrin, and longikaurin A. Key AD genes prostaglandin-endoperoxide synthase-2 (, cyclooxygenase-2) and acetylcholinesterase () were linked to SCF compounds. In the rats with AD induced by bilaterally infusing amyloid-β (25-35) into the hippocampus, the 0.5% SCF intake mitigated hippocampal amyloid-β deposition, neuroinflammation, memory deficits, and dysregulated glucose and lipid metabolism versus the AD controls. SCF reduced hippocampal AChE activity, inflammatory cytokine expression related to , and malondialdehyde contents and preserved neuronal cell survival-related factors such as brain-derived neurotrophic factor and ciliary neurotrophic factor similar to normal rats. The neuroprotective effects validated the network analysis findings.
SCF could be a potential AD therapeutic agent by activating the parasympathetic nervous system to reduce hippocampal oxidative stress and inflammation, warranting further clinical investigations of its efficacy.
背景/目的：五味子（SCF）是一种传统药用植物，含有木脂素，可通过减轻胰岛素抵抗改善葡萄糖代谢。我们旨在通过网络药理学分析研究 SCF 对阿尔茨海默病（AD）的治疗潜力和作用机制，然后在 AD 大鼠模型中进行实验验证。
通过网络药理学分析评估 SCF 生物活性化合物的生物活性。通过将淀粉样β肽（Aβ）（25-35）注入海马诱导 Aβ 积累来生成 AD 大鼠模型。AD 大鼠在高脂肪饮食中分别喂食 0.5%糊精（AD-Con）或 0.5% SCF（AD-SCF 组）七周。正常/对照组大鼠接受 Aβ（35-25）输注（无 Aβ 沉积）并喂食对照饮食（正常-C）。评估 Aβ 沉积、记忆功能、炎症和葡萄糖/脂质代谢。
网络分析显示 AD 相关靶标与生物活性 SCF 化合物之间存在显著交集，如戈米辛 A、五味子素和长梗冬青 A。关键的 AD 基因前列腺素内过氧化物合酶-2（COX-2）和乙酰胆碱酯酶（AchE）与 SCF 化合物有关。在双侧将淀粉样β（25-35）注入海马诱导的 AD 大鼠中，与 AD 对照组相比，摄入 0.5% SCF 可减轻海马 Aβ 沉积、神经炎症、记忆缺陷和葡萄糖/脂质代谢紊乱。SCF 降低了海马 AChE 活性、与 COX-2 相关的炎症细胞因子表达和丙二醛含量，并保存了神经元细胞存活相关因子，如脑源性神经营养因子和睫状神经营养因子，与正常大鼠相似。神经保护作用验证了网络分析的结果。
SCF 可能是一种潜在的 AD 治疗药物，通过激活副交感神经系统来减轻海马氧化应激和炎症，值得进一步研究其疗效。
