Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, 45 Changchun Street, Beijing, China.
Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, 45 Changchun Street, Beijing, China; Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China; Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China; Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China.
Biochem Biophys Res Commun. 2022 Jan 29;590:14-19. doi: 10.1016/j.bbrc.2021.12.071. Epub 2021 Dec 21.
Alzheimer's disease (AD), has caused a mass of disability and mortality in elder populations, which increases global health burden. There are still limited effective disease-modifying drugs. Alleviating microglia-evoked neuroinflammation has become a promising treatment strategy for AD. Ginsenoside Compound K has been demonstrated to exhibit anti-inflammatory and neuroprotective benefits. Here we measured the effects of Ginsenoside Compound K in inhibiting amyloid-induced microglia inflammation and the possible molecular mechanisms and target of action in vitro.
The cytotoxicity of all chemical reagents on BV2 cells were evaluated using the MTT assay. qRT-PCR and ELISA were carried out to detect the inflammatory cytokines levels. Western blot was utilized to determine the effect of Ginsenoside Compound K on the nuclear factor-κB (NF-κB) p65 nuclear translocation. Antagonist Receptor Associated Protein (RAP) was used to verify the engagement of low-density lipoprotein receptor-related protein 1(LRP1).
Ginsenoside Compound K diminished inflammatory cytokine production and reversed NF-κB p65 nuclear translocation induced by Aβ oligomers. LRP1 expression was up-regulated by Ginsenoside Compound K. When LRP1 was blocked by antagonist RAP, the protective effect of Ginsenoside Compound K was massively eliminated.
These observations provide evidence for anti-inflammatory effect of Ginsenoside Compound K through NF-κB pathway via LRP1 activation, and support further evaluation of Ginsenoside Compound K as a potential effective modulator for AD.
阿尔茨海默病（AD）在老年人群中导致大量残疾和死亡，增加了全球健康负担。目前仍然缺乏有效的疾病修饰药物。减轻小胶质细胞引发的神经炎症已成为治疗 AD 的一种有前途的策略。人参皂苷化合物 K 已被证明具有抗炎和神经保护作用。在这里，我们测量了人参皂苷化合物 K 在抑制淀粉样蛋白诱导的小胶质细胞炎症中的作用及其在体外的可能作用机制和作用靶点。
使用 MTT 测定法评估所有化学试剂对 BV2 细胞的细胞毒性。qRT-PCR 和 ELISA 用于检测炎症细胞因子水平。Western blot 用于确定人参皂苷化合物 K 对核因子-κB（NF-κB）p65核易位的影响。使用受体相关蛋白（RAP）来验证低密度脂蛋白受体相关蛋白 1（LRP1）的参与。
人参皂苷化合物 K 可减少炎症细胞因子的产生，并逆转 Aβ 寡聚体诱导的 NF-κB p65 核易位。人参皂苷化合物 K 上调了 LRP1 的表达。当 LRP1 被拮抗剂 RAP 阻断时，人参皂苷化合物 K 的保护作用大大消除。
这些观察结果为通过 LRP1 激活 NF-κB 途径提供了人参皂苷化合物 K 的抗炎作用的证据，并支持进一步评估人参皂苷化合物 K 作为 AD 的潜在有效调节剂。
