Dual-targeted liposomes delivering ginsenoside CK attenuate cerebral ischemia-reperfusion injury by suppressing PANoptosis via O-GlcNAcylation of RIPK1/RIPK3

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2026-01-18 DOI:10.1016/j.jgr.2026.100978

Suping Li , Ping Ni , Haifeng Shao , Qiao Chen , Jing Fu , Fei Xu , Chaohui He , Gang Li

{"title":"Dual-targeted liposomes delivering ginsenoside CK attenuate cerebral ischemia-reperfusion injury by suppressing PANoptosis via O-GlcNAcylation of RIPK1/RIPK3","authors":"Suping Li , Ping Ni , Haifeng Shao , Qiao Chen , Jing Fu , Fei Xu , Chaohui He , Gang Li","doi":"10.1016/j.jgr.2026.100978","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke remains a major cause of mortality and disability worldwide, with limited treatment options. This study aimed to develop dual-targeted liposomes containing ginsenoside CK and evaluate their neuroprotective effects against cerebral ischemia-reperfusion injury.</div></div><div><h3>Methods</h3><div>Liposomes modified with transferrin, rabies virus glycoprotein, and ginsenoside CK were prepared and characterized. Their uptake and protective effects were assessed in neuronal and endothelial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). A rat model of transient middle cerebral artery occlusion was used to evaluate neuroprotection <em>in vivo</em>. Molecular docking, surface plasmon resonance, and co-immunoprecipitation were performed to investigate the mechanism. Western blot data were analyzed by densitometric quantification.</div></div><div><h3>Results</h3><div>The dual-targeted liposomes exhibited enhanced cellular uptake and brain accumulation. They protected against mitochondrial fission and PANoptosis <em>in vitro</em> and reduced infarct volume and neuronal death <em>in vivo</em>. Quantitative analysis revealed that the ginsenoside CK-containing liposomes significantly reversed OGD/R-induced changes in apoptotic, pyroptotic, and necroptotic markers. Mechanistically, ginsenoside CK bound to O-GlcNAcase with a K<sub>D</sub> = 3.89 μM and enhanced O-GlcNAcylation of RIPK1/RIPK3, disrupting PANoptosome formation.</div></div><div><h3>Conclusion</h3><div>Dual-targeted liposomes containing ginsenoside CK represent a promising therapeutic strategy for cerebral ischemia-reperfusion injury. This approach overcomes blood-brain barrier limitations through targeted delivery. Besides, ginsenoside CK as a liposome component inhibits PANoptosis via enhanced protein O-GlcNAcylation. Further optimization and safety studies are warranted to advance this strategy toward clinical application.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 3","pages":"Article 100978"},"PeriodicalIF":7.5000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ginseng Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1226845326000047","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Ischemic stroke remains a major cause of mortality and disability worldwide, with limited treatment options. This study aimed to develop dual-targeted liposomes containing ginsenoside CK and evaluate their neuroprotective effects against cerebral ischemia-reperfusion injury.

Methods

Liposomes modified with transferrin, rabies virus glycoprotein, and ginsenoside CK were prepared and characterized. Their uptake and protective effects were assessed in neuronal and endothelial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). A rat model of transient middle cerebral artery occlusion was used to evaluate neuroprotection in vivo. Molecular docking, surface plasmon resonance, and co-immunoprecipitation were performed to investigate the mechanism. Western blot data were analyzed by densitometric quantification.

Results

The dual-targeted liposomes exhibited enhanced cellular uptake and brain accumulation. They protected against mitochondrial fission and PANoptosis in vitro and reduced infarct volume and neuronal death in vivo. Quantitative analysis revealed that the ginsenoside CK-containing liposomes significantly reversed OGD/R-induced changes in apoptotic, pyroptotic, and necroptotic markers. Mechanistically, ginsenoside CK bound to O-GlcNAcase with a K_D = 3.89 μM and enhanced O-GlcNAcylation of RIPK1/RIPK3, disrupting PANoptosome formation.

Conclusion

Dual-targeted liposomes containing ginsenoside CK represent a promising therapeutic strategy for cerebral ischemia-reperfusion injury. This approach overcomes blood-brain barrier limitations through targeted delivery. Besides, ginsenoside CK as a liposome component inhibits PANoptosis via enhanced protein O-GlcNAcylation. Further optimization and safety studies are warranted to advance this strategy toward clinical application.

Abstract Image

查看原文本刊更多论文

传递人参皂苷CK的双靶向脂质体通过o - glcn酰化RIPK1/RIPK3抑制PANoptosis减轻脑缺血再灌注损伤

背景：在世界范围内，非化学性脑卒中仍然是导致死亡和残疾的主要原因，治疗选择有限。本研究旨在制备含人参皂苷CK的双靶向脂质体，并评价其对脑缺血再灌注损伤的神经保护作用。方法制备转铁蛋白、狂犬病毒糖蛋白和人参皂苷CK修饰的脂质体，并对其进行表征。在缺氧-葡萄糖剥夺/再氧化（OGD/R）的神经细胞和内皮细胞中评估了它们的摄取和保护作用。采用一过性大脑中动脉闭塞大鼠模型，在体内评价其神经保护作用。通过分子对接、表面等离子体共振和共免疫沉淀来研究其机制。Western blot数据采用密度定量分析。结果双靶向脂质体表现出增强的细胞摄取和脑蓄积。它们在体外对线粒体分裂和PANoptosis有保护作用，并在体内减少梗死体积和神经元死亡。定量分析显示，含人参皂苷ck脂质体可显著逆转OGD/ r诱导的凋亡、焦亡和坏死标志物的变化。机制上，人参皂苷CK以KD = 3.89 μM结合O-GlcNAcase，增强了RIPK1/RIPK3的o - glcn酰化，破坏了PANoptosome的形成。结论含人参皂苷CK的双靶向脂质体是治疗脑缺血再灌注损伤的有效方法。这种方法通过靶向递送克服了血脑屏障的限制。此外，人参皂苷CK作为脂质体组分通过增强蛋白o - glcn酰化抑制PANoptosis。进一步的优化和安全性研究是必要的，以推进该策略的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.