@article{Wang2026, 
author = {Qi Wang and Xiaomeng Guo and Meijing Li and Nan Nan and Zekuan Zhang and Zhimin Song and Ziwei Zhou and Nan Zhang and Rui He and Jing Li and Hui Zhao and Renhui Liu and Miao Qu and Muxin Gong},
title = {Self-assembled nanoaggregates in Wuzhuyu decoction: formation, absorption, transport, and alleviation of chronic migraine},
year = {2026},
journal = {Chinese Journal of Natural Medicines},
volume = {24},
number = {8},
pages = {956-971},
keywords = {Nanoaggregates, Wuzhuyu decoction, Chronic migraine, Self-assemble, Absorption, IL-33/ST2/TRPA1},
url = {https://www.sciopen.com/article/10.1016/S1875-5364(26)61201-0},
doi = {10.1016/S1875-5364(26)61201-0},
abstract = {Self-assembled nanoaggregates (SANs) derived from herbal decoctions have emerged as promising natural nanomedicines. However, their formation patterns in multi-herb formulations and therapeutic roles in central nervous system disorders remain unclear. Wuzhuyu decoction (WZYD) is a classical formula for migraine treatment. Here, we reveal that SANs in WZYD (N-WZYDs) are formed through synergistic interactions among multiple herbal ingredients with Euodiae Fructus as the focus. N-WZYDs consisted mainly of proteoglycan scaffolds and small-molecule active components. In chronic migraine (CM) rat models, N-WZYDs significantly alleviated symptoms with efficacy comparable to that of WZYD, potentially via inhibition of the IL-33/ST2/TRPA1 signaling pathway. In Caco-2 cells, transport studies indicated that ginsenoside Rg1, dehydroevodiamine, and rutaevin were poorly absorbed, whereas evodiamine and 6-gingerol were moderately absorbed but significantly active in efflux, indicating the intestine as a key site of action. As an oral medication, intact N-WZYDs accumulated primarily in the intestines and could be internalized by Caco-2 and enterochromaffin cells. Crucially, N-WZYDs promoted serotonin release from enterochromaffin cells more effectively than free active molecules alone and increased peripheral serotonin levels, thereby alleviating CM. By investigating the formation patterns, anti-CM mechanisms, and absorption behaviors of N-WZYDs, this study elucidated their material basis and brain−intestine interactions in treating CM, supporting their further development as therapeutic agents or drug delivery systems.}
}