Houttuynia cordata-derived nanoparticles stabilize mitochondrial dynamics to alleviate ulcerative colitis via the Nrf2/Ho-1 pathways.

BACKGROUND

Ulcerative colitis (UC), a chronic inflammatory bowel disease, faces limited treatment efficacy and safety concerns. Extracellular vesicles (EVs) offer a promising nanoplatform for targeted therapy.

PURPOSE: This study aimed to isolate and characterize houttuynia cordata-derived nanoparticles (HDNPs) and evaluate their therapeutic potential in UC by targeting dual pathological axes: mitochondrial dynamics dysregulation and oxidative-inflammatory cascades, aiming to address unmet needs in current UC therapies.

METHODS

In vitro studies using LPS-stimulated Caco-2 cells (modeling inflamed intestinal epithelia) to evaluate mitochondrial dynamics, Nrf2/Ho-1 activation, oxidative stress. In vivo validation was performed in a DSS-induced murine UC model, assessing clinical parameters, histopathology and molecular markers.

RESULTS

HDNPs administration significantly attenuated DSS-induced weight loss and elevated disease activity index, while preserving intestinal mucosal integrity. In vitro, HDNPs markedly reduced intracellular oxidative markers, activated Nrf2 signaling, and upregulated Ho-1 synthesis. Notably, Nrf2 inhibition abolished HDNPs' protective effects, confirming the critical role of this pathway in mediating therapeutic outcomes.

CONCLUSION

HDNPs stabilize mitochondrial dynamics to restore epithelial energy homeostasis and activating the Nrf2/Ho-1 axis to suppress oxidative-inflammatory cascades, addressing critical limitations of conventional UC therapies and offering translational potential for clinical application.