{"title":"紫苏细胞外囊泡的抗炎和抗氧化作用:来自斑马鱼模型的见解","authors":"Jinghong Huang , Linxin Chen , Wenhua Li , Chih-Jung Chang","doi":"10.1016/j.molimm.2025.04.008","DOIUrl":null,"url":null,"abstract":"<div><div>Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of <em>Perilla frutescens</em>-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. <em>In vivo</em> studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the <em>mpx</em> and <em>lcp1</em> genes via <em>in situ</em> hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to H<sub>2</sub>O<sub>2</sub>-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 126-138"},"PeriodicalIF":3.2000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-inflammatory and antioxidative effects of Perilla frutescens-derived extracellular vesicles: Insights from Zebrafish models\",\"authors\":\"Jinghong Huang , Linxin Chen , Wenhua Li , Chih-Jung Chang\",\"doi\":\"10.1016/j.molimm.2025.04.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of <em>Perilla frutescens</em>-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. <em>In vivo</em> studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the <em>mpx</em> and <em>lcp1</em> genes via <em>in situ</em> hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to H<sub>2</sub>O<sub>2</sub>-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.</div></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":\"182 \",\"pages\":\"Pages 126-138\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-04-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0161589025001051\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589025001051","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Anti-inflammatory and antioxidative effects of Perilla frutescens-derived extracellular vesicles: Insights from Zebrafish models
Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of Perilla frutescens-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. In vivo studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the mpx and lcp1 genes via in situ hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to H2O2-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.