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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03567-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 1477-3155 |