Intranasal Fritillaria taipaiensis nanovesicles alleviate acute lung injury via the lung-brain axis
- 1Chengdu University of Traditional Chinese Medicine
Abstract
Acute lung injury (ALI) is a severe inflammatory syndrome frequently complicated by brain injury, which worsens outcomes. Here, we explored whether regulation of the lung-brain axis represents a therapeutic strategy for the management of ALI. We show that intranasal administration of Fritillaria taipaiensis-derived exosome-like nanovesicles (Ft-ELNs) ameliorates LPS-induced ALI and ALI-associated hypothalamic inflammation in mice. Ft-ELNs preferentially accumulate in the lungs, inhibiting TRPV1 in both the lungs and the hypothalamus to establish the lung-brain axis. In parallel, Ft-ELNs primarily regulate systemic humoral immunity by inhibiting the VEGFR1/PI3K/AKT/NF?B signaling pathway. In vitro experiments further confirmed that Ft-ELNs are efficiently internalized by alveolar epithelial MLE-12 cells, exerting protective effects by suppressing VEGFR1 expression. Mechanistically, we identified Ft-miR1 of Ft-ELNs as the key functional effector that directly targets the Flt1 3'UTR to inhibit VEGFR1 expression. These data suggest that Ft-ELNs attenuate lung-brain axis inflammation by targeting VEGFR1 and may hold potential as novel therapeutic agents for the treatment of severe ALI.
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BibTeX
@misc{rao2026intranasal,
title = {{Intranasal Fritillaria taipaiensis nanovesicles alleviate acute lung injury via the lung-brain axis}},
author = {H. Rao and J. Pan and J. Guo and X. Song and S. Gong and T. Zhou and Q. Wu and Y. Huang and W. Nie and C. Peng and Z. Li and C. Ren and J. Pei},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749870},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749870v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Intranasal Fritillaria taipaiensis nanovesicles alleviate acute lung injury via the lung-brain axis
AU - H. Rao
AU - J. Pan
AU - J. Guo
AU - X. Song
AU - S. Gong
AU - T. Zhou
AU - Q. Wu
AU - Y. Huang
AU - W. Nie
AU - C. Peng
AU - Z. Li
AU - C. Ren
AU - J. Pei
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749870
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749870v1
AB - Acute lung injury (ALI) is a severe inflammatory syndrome frequently complicated by brain injury, which worsens outcomes. Here, we explored whether regulation of the lung-brain axis represents a therapeutic strategy for the management of ALI. We show that intranasal administration of Fritillaria taipaiensis-derived exosome-like nanovesicles (Ft-ELNs) ameliorates LPS-induced ALI and ALI-associated hypothalamic inflammation in mice. Ft-ELNs preferentially accumulate in the lungs, inhibiting TRPV1 in both the lungs and the hypothalamus to establish the lung-brain axis. In parallel, Ft-ELNs primarily regulate systemic humoral immunity by inhibiting the VEGFR1/PI3K/AKT/NF?B signaling pathway. In vitro experiments further confirmed that Ft-ELNs are efficiently internalized by alveolar epithelial MLE-12 cells, exerting protective effects by suppressing VEGFR1 expression. Mechanistically, we identified Ft-miR1 of Ft-ELNs as the key functional effector that directly targets the Flt1 3'UTR to inhibit VEGFR1 expression. These data suggest that Ft-ELNs attenuate lung-brain axis inflammation by targeting VEGFR1 and may hold potential as novel therapeutic agents for the treatment of severe ALI.
ER -