Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease

Abstract Plant-derived extracellular vesicles (EVs) show health benefits. Gardenia jasminoides Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) u...

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Main Authors: Wen Chen, Haobo Wang, Xiang Ye, Xingkai Hao, Fujie Yan, Jian Wu, Danyang Li, Yan Wang, Lizhou Xu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01044-6
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author Wen Chen
Haobo Wang
Xiang Ye
Xingkai Hao
Fujie Yan
Jian Wu
Danyang Li
Yan Wang
Lizhou Xu
author_facet Wen Chen
Haobo Wang
Xiang Ye
Xingkai Hao
Fujie Yan
Jian Wu
Danyang Li
Yan Wang
Lizhou Xu
author_sort Wen Chen
collection DOAJ
description Abstract Plant-derived extracellular vesicles (EVs) show health benefits. Gardenia jasminoides Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) using rotenone (Rot)-induced Parkinsonism models in dopaminergic PC12 neuron cells and Caenorhabditis elegans. PD features apoptosis in dopaminergic neurons, while GDEVs alleviate PD by mitigating mitochondrial-mediated apoptosis. Specifically, GDEVs improve Rot-induced mitochondrial dysfunction to reduce cytochrome C release and apoptosis. Consequently, GDEVs reduce the risk of PD by lowering α-synuclein levels and regulating dopamine release. RNA sequencing and subsequent studies showed that GDEVs reduce p38 MAPK and p53 phosphorylation levels, and increase the Bcl-2/Bax ratio to prevent apoptosis in PC12 cells. In Caenorhabditis elegans, we verified that GDEVs reduce PD progression by increasing dopaminergic neurons using BZ555 mutants, and enhance dopamine release and motility. This study highlights the therapeutic potential of GDEVs in preventing neurodegenerative diseases.
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issn 2373-8057
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series npj Parkinson's Disease
spelling doaj-art-0adf84b65bde4231b6f84cd9776bbc6b2025-08-20T03:03:32ZengNature Portfolionpj Parkinson's Disease2373-80572025-07-0111111610.1038/s41531-025-01044-6Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s diseaseWen Chen0Haobo Wang1Xiang Ye2Xingkai Hao3Fujie Yan4Jian Wu5Danyang Li6Yan Wang7Lizhou Xu8College of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityCollege of Food and Health, Zhejiang Agriculture and Forestry UniversityCollege of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityCollege of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityCollege of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityCollege of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityResearch Center, The Seventh Affiliated Hospital, Sun Yat-sen University; Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational ResearchCollege of Food and Health, Zhejiang Agriculture and Forestry UniversityCollege of Biosystems Engineering and Food Science & ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang UniversityAbstract Plant-derived extracellular vesicles (EVs) show health benefits. Gardenia jasminoides Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) using rotenone (Rot)-induced Parkinsonism models in dopaminergic PC12 neuron cells and Caenorhabditis elegans. PD features apoptosis in dopaminergic neurons, while GDEVs alleviate PD by mitigating mitochondrial-mediated apoptosis. Specifically, GDEVs improve Rot-induced mitochondrial dysfunction to reduce cytochrome C release and apoptosis. Consequently, GDEVs reduce the risk of PD by lowering α-synuclein levels and regulating dopamine release. RNA sequencing and subsequent studies showed that GDEVs reduce p38 MAPK and p53 phosphorylation levels, and increase the Bcl-2/Bax ratio to prevent apoptosis in PC12 cells. In Caenorhabditis elegans, we verified that GDEVs reduce PD progression by increasing dopaminergic neurons using BZ555 mutants, and enhance dopamine release and motility. This study highlights the therapeutic potential of GDEVs in preventing neurodegenerative diseases.https://doi.org/10.1038/s41531-025-01044-6
spellingShingle Wen Chen
Haobo Wang
Xiang Ye
Xingkai Hao
Fujie Yan
Jian Wu
Danyang Li
Yan Wang
Lizhou Xu
Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
npj Parkinson's Disease
title Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
title_full Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
title_fullStr Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
title_full_unstemmed Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
title_short Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease
title_sort gardenia derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis mediated parkinson s disease
url https://doi.org/10.1038/s41531-025-01044-6
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