人参皂苷C-K通过调节小胶质细胞-神经元相互作用抑制Aβ寡聚物诱导的阿尔茨海默病病理进展

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-05-21 DOI:10.1016/j.ibneur.2025.05.007

Chenghu Xie , Cunxin Zhang , Kefeng Zhang , Shanshan Zhang

{"title":"人参皂苷C-K通过调节小胶质细胞-神经元相互作用抑制Aβ寡聚物诱导的阿尔茨海默病病理进展","authors":"Chenghu Xie , Cunxin Zhang , Kefeng Zhang , Shanshan Zhang","doi":"10.1016/j.ibneur.2025.05.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease is a progressive neurodegenerative disorder. Current therapeutic agents primarily focus on symptom alleviation and fail to effectively halt disease progression. Therefore, there is a need to develop novel therapeutic strategies, particularly those involving natural active compounds with multi-target actions.</div></div><div><h3>Objective</h3><div>To investigate the intervention effects and multi-target regulatory mechanisms of Ginsenoside C-K (GCK) on β-amyloid (Aβ) oligomer-induced Alzheimer's disease (AD) pathological progression.</div></div><div><h3>Methods</h3><div>BV2 microglia and HT22 neurons were used as in vitro models. Cell viability was measured via CCK-8 assay, cell migration ability assessed by scratch assay, and apoptosis rate analyzed using Annexin V/PI dual staining. A conditioned medium (CM) strategy was employed to validate microglia-neuron interactions. Western blot was performed to detect key NF-κB signaling pathway proteins (p-IκBα, p-p65) and inflammatory cytokines (TNF-α, IL-1β).</div></div><div><h3>Results</h3><div>GCK pretreatment significantly ameliorated Aβ₁₋₄₂ oligomer-induced BV2 cell dysfunction (viability recovery rate >80 %, p < 0.01), suppressed pro-inflammatory cytokine secretion (TNF-α reduced by 62.3 %, IL-1β by 57.8 %), and inhibited NF-κB pathway activation (p-IκBα/p-p65 expression downregulated >50 %). In HT22 neurons, GCK directly counteracted Aβ toxicity (apoptosis rate decreased from 38.7 % to 15.2 %) and exerted indirect neuroprotection by modulating microglia-derived conditioned medium (CM2 group showed a 2.1-fold increase in neuronal viability compared to CM1).</div></div><div><h3>Conclusion</h3><div>GCK mitigates AD pathology through dual mechanisms-direct inhibition of Aβ neurotoxicity and indirect regulation of microglial homeostasis-with NF-κB signaling suppression as a core mechanism. This study provides new experimental evidence for natural product-based multi-target AD therapies, though further animal studies are required to validate its in vivo efficacy and safety.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 783-793"},"PeriodicalIF":2.9000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ginsenoside C-K inhibits Aβ oligomer-induced Alzheimer's disease pathology progression by regulating microglia-neuron interactions\",\"authors\":\"Chenghu Xie , Cunxin Zhang , Kefeng Zhang , Shanshan Zhang\",\"doi\":\"10.1016/j.ibneur.2025.05.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Alzheimer’s disease is a progressive neurodegenerative disorder. Current therapeutic agents primarily focus on symptom alleviation and fail to effectively halt disease progression. Therefore, there is a need to develop novel therapeutic strategies, particularly those involving natural active compounds with multi-target actions.</div></div><div><h3>Objective</h3><div>To investigate the intervention effects and multi-target regulatory mechanisms of Ginsenoside C-K (GCK) on β-amyloid (Aβ) oligomer-induced Alzheimer's disease (AD) pathological progression.</div></div><div><h3>Methods</h3><div>BV2 microglia and HT22 neurons were used as in vitro models. Cell viability was measured via CCK-8 assay, cell migration ability assessed by scratch assay, and apoptosis rate analyzed using Annexin V/PI dual staining. A conditioned medium (CM) strategy was employed to validate microglia-neuron interactions. Western blot was performed to detect key NF-κB signaling pathway proteins (p-IκBα, p-p65) and inflammatory cytokines (TNF-α, IL-1β).</div></div><div><h3>Results</h3><div>GCK pretreatment significantly ameliorated Aβ₁₋₄₂ oligomer-induced BV2 cell dysfunction (viability recovery rate >80 %, p < 0.01), suppressed pro-inflammatory cytokine secretion (TNF-α reduced by 62.3 %, IL-1β by 57.8 %), and inhibited NF-κB pathway activation (p-IκBα/p-p65 expression downregulated >50 %). In HT22 neurons, GCK directly counteracted Aβ toxicity (apoptosis rate decreased from 38.7 % to 15.2 %) and exerted indirect neuroprotection by modulating microglia-derived conditioned medium (CM2 group showed a 2.1-fold increase in neuronal viability compared to CM1).</div></div><div><h3>Conclusion</h3><div>GCK mitigates AD pathology through dual mechanisms-direct inhibition of Aβ neurotoxicity and indirect regulation of microglial homeostasis-with NF-κB signaling suppression as a core mechanism. This study provides new experimental evidence for natural product-based multi-target AD therapies, though further animal studies are required to validate its in vivo efficacy and safety.</div></div>\",\"PeriodicalId\":13195,\"journal\":{\"name\":\"IBRO Neuroscience Reports\",\"volume\":\"18 \",\"pages\":\"Pages 783-793\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-05-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IBRO Neuroscience Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667242125000740\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"IBRO Neuroscience Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667242125000740","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

阿尔茨海默病是一种进行性神经退行性疾病。目前的治疗药物主要集中在缓解症状，不能有效地阻止疾病进展。因此，有必要开发新的治疗策略，特别是涉及具有多靶点作用的天然活性化合物的治疗策略。目的探讨人参皂苷C-K （GCK）对β-淀粉样蛋白（Aβ）寡聚物诱导的阿尔茨海默病（AD）病理进展的干预作用及多靶点调控机制。方法采用sbv2小胶质细胞和HT22神经元作为体外模型。CCK-8法检测细胞活力，划痕法检测细胞迁移能力，Annexin V/PI双染色检测细胞凋亡率。采用条件培养基（CM）策略验证小胶质细胞与神经元的相互作用。Western blot检测NF-κB信号通路关键蛋白（p -κB α、p-p65）和炎症因子（TNF-α、IL-1β）。结果gck预处理显著改善Aβ₁₄₂寡聚物诱导的BV2细胞功能障碍（活力恢复率>；80 %,p <； 0.01），抑制促炎细胞因子分泌（TNF-α减少62.3 %，IL-1β减少57.8 %），抑制NF-κB通路激活（p -κB α/p-p65表达下调>；50 %）。在HT22神经元中，GCK直接抵消了a β毒性（细胞凋亡率从38.7 %下降到15.2 %），并通过调节小胶质细胞来源的条件培养基发挥间接神经保护作用（CM2组的神经元活力比CM1组增加了2.1倍）。结论ck通过直接抑制a β神经毒性和间接调节小胶质细胞稳态的双重机制减轻AD病理，其中NF-κB信号传导抑制是其核心机制。该研究为基于天然产物的多靶点阿尔茨海默病治疗提供了新的实验证据，但还需要进一步的动物实验来验证其体内有效性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Ginsenoside C-K inhibits Aβ oligomer-induced Alzheimer's disease pathology progression by regulating microglia-neuron interactions

Background

Alzheimer’s disease is a progressive neurodegenerative disorder. Current therapeutic agents primarily focus on symptom alleviation and fail to effectively halt disease progression. Therefore, there is a need to develop novel therapeutic strategies, particularly those involving natural active compounds with multi-target actions.

Objective

To investigate the intervention effects and multi-target regulatory mechanisms of Ginsenoside C-K (GCK) on β-amyloid (Aβ) oligomer-induced Alzheimer's disease (AD) pathological progression.

Methods

BV2 microglia and HT22 neurons were used as in vitro models. Cell viability was measured via CCK-8 assay, cell migration ability assessed by scratch assay, and apoptosis rate analyzed using Annexin V/PI dual staining. A conditioned medium (CM) strategy was employed to validate microglia-neuron interactions. Western blot was performed to detect key NF-κB signaling pathway proteins (p-IκBα, p-p65) and inflammatory cytokines (TNF-α, IL-1β).

Results

GCK pretreatment significantly ameliorated Aβ₁₋₄₂ oligomer-induced BV2 cell dysfunction (viability recovery rate >80 %, p < 0.01), suppressed pro-inflammatory cytokine secretion (TNF-α reduced by 62.3 %, IL-1β by 57.8 %), and inhibited NF-κB pathway activation (p-IκBα/p-p65 expression downregulated >50 %). In HT22 neurons, GCK directly counteracted Aβ toxicity (apoptosis rate decreased from 38.7 % to 15.2 %) and exerted indirect neuroprotection by modulating microglia-derived conditioned medium (CM2 group showed a 2.1-fold increase in neuronal viability compared to CM1).

Conclusion

GCK mitigates AD pathology through dual mechanisms-direct inhibition of Aβ neurotoxicity and indirect regulation of microglial homeostasis-with NF-κB signaling suppression as a core mechanism. This study provides new experimental evidence for natural product-based multi-target AD therapies, though further animal studies are required to validate its in vivo efficacy and safety.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊