Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation
Abstract Edible plant derived extracellular vesicle-like particles (EVLPs) have garnered attention as potential therapeutic agents for chronic inflammatory diseases. Prunus mume (PM) is a functional fruit known for its gastrointestinal benefits, yet the detail material basis and potential mechanism...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03567-9 |
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| author | Qi Lv Hongqiong Yang Ying Xie Xinjie Huang Zhiqi Yan Yingshan Lv Yifan Cui Lihong Hu Hongzhi Qiao |
| author_facet | Qi Lv Hongqiong Yang Ying Xie Xinjie Huang Zhiqi Yan Yingshan Lv Yifan Cui Lihong Hu Hongzhi Qiao |
| author_sort | Qi Lv |
| collection | DOAJ |
| description | Abstract Edible plant derived extracellular vesicle-like particles (EVLPs) have garnered attention as potential therapeutic agents for chronic inflammatory diseases. Prunus mume (PM) is a functional fruit known for its gastrointestinal benefits, yet the detail material basis and potential mechanism remain unclear. Here, we reported that oral administration of prunus mume derived EVLPs (PM-EVLPs) substantially mitigated experimental colitis in mice. The in vivo bio-distribution analysis revealed that PM-EVLPs specifically targeted inflamed colon of colitis mice. Further in vitro studies demonstrated that PM-EVLPs were predominantly internalized by macrophages. The combined treatment with clodronate liposomes confirmed that macrophage was the target cell for PM-EVLPs-mediated anti-colitis activity. Mechanistically, PM-EVLPs selectively inhibited caspase-1 auto-cleavage and IL-1β secretion caused by NLRP3 inflammasome activation, while exerting minimal impact on AIM2, NLRP1 or NLRC4 inflammasome activation. Excluding the effects on mitochondrial ROS generation, K+ efflux or Ca2+ influx, PM-EVLPs disrupted the NEK7-NLRP3 interaction, thereby preventing NLRP3 inflammasome assembly. Notably, the inhibitory activity was attributed to RNAs rather than lipids or proteins within PM-EVLPs. Deep RNA sequencing, coupled with the application of miRNA mimics/inhibitors identified miR159 as the material basis for PM-EVLPs’ inhibition of NLRP3 inflammasome activation and anti-colitis efficacy. Collectively, these findings suggest that PM-EVLPs represent a promising nanomedicine with potential as a novel therapeutic strategy for colitis and deserves further investigation and development. |
| format | Article |
| id | doaj-art-cf61e972274442a4bea29e20772f992d |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-cf61e972274442a4bea29e20772f992d2025-08-20T03:42:57ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123111910.1186/s12951-025-03567-9Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activationQi Lv0Hongqiong Yang1Ying Xie2Xinjie Huang3Zhiqi Yan4Yingshan Lv5Yifan Cui6Lihong Hu7Hongzhi Qiao8Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese MedicineAbstract Edible plant derived extracellular vesicle-like particles (EVLPs) have garnered attention as potential therapeutic agents for chronic inflammatory diseases. Prunus mume (PM) is a functional fruit known for its gastrointestinal benefits, yet the detail material basis and potential mechanism remain unclear. Here, we reported that oral administration of prunus mume derived EVLPs (PM-EVLPs) substantially mitigated experimental colitis in mice. The in vivo bio-distribution analysis revealed that PM-EVLPs specifically targeted inflamed colon of colitis mice. Further in vitro studies demonstrated that PM-EVLPs were predominantly internalized by macrophages. The combined treatment with clodronate liposomes confirmed that macrophage was the target cell for PM-EVLPs-mediated anti-colitis activity. Mechanistically, PM-EVLPs selectively inhibited caspase-1 auto-cleavage and IL-1β secretion caused by NLRP3 inflammasome activation, while exerting minimal impact on AIM2, NLRP1 or NLRC4 inflammasome activation. Excluding the effects on mitochondrial ROS generation, K+ efflux or Ca2+ influx, PM-EVLPs disrupted the NEK7-NLRP3 interaction, thereby preventing NLRP3 inflammasome assembly. Notably, the inhibitory activity was attributed to RNAs rather than lipids or proteins within PM-EVLPs. Deep RNA sequencing, coupled with the application of miRNA mimics/inhibitors identified miR159 as the material basis for PM-EVLPs’ inhibition of NLRP3 inflammasome activation and anti-colitis efficacy. Collectively, these findings suggest that PM-EVLPs represent a promising nanomedicine with potential as a novel therapeutic strategy for colitis and deserves further investigation and development.https://doi.org/10.1186/s12951-025-03567-9PM-EVLPsUlcerative colitisNLRP3 inflammasomeNEK7-NLRP3 interactionmiR159 |
| spellingShingle | Qi Lv Hongqiong Yang Ying Xie Xinjie Huang Zhiqi Yan Yingshan Lv Yifan Cui Lihong Hu Hongzhi Qiao Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation Journal of Nanobiotechnology PM-EVLPs Ulcerative colitis NLRP3 inflammasome NEK7-NLRP3 interaction miR159 |
| title | Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation |
| title_full | Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation |
| title_fullStr | Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation |
| title_full_unstemmed | Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation |
| title_short | Prunus mume derived extracellular vesicle-like particles alleviate experimental colitis via disrupting NEK7-NLRP3 interaction and inflammasome activation |
| title_sort | prunus mume derived extracellular vesicle like particles alleviate experimental colitis via disrupting nek7 nlrp3 interaction and inflammasome activation |
| topic | PM-EVLPs Ulcerative colitis NLRP3 inflammasome NEK7-NLRP3 interaction miR159 |
| url | https://doi.org/10.1186/s12951-025-03567-9 |
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