Tuberostemonine ameliorates Alzheimer's disease pathology by suppression of the p38 MAPK signaling pathway.

Authors

Yingzhou Li, Xiaoxia Xu, Ziyao Meng, Linjie Chen, Qin Yu, Ruya Wang, Yiyu Ren, Fan Chen, Guang Liang, Xia Zhao, Houming Yu, Jurui Wei

Published in

iScience. Volume 29. Issue 8. Pages 116887. Aug 21, 2026. Epub Jul 21, 2026.

Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with limited therapeutic options. Here, we report that tuberostemonine (Tub), an alkaloid from Stemona tuberosa, exerts neuroprotective effects in AD models. In Aβ_1-42-treated PC12 cells, Tub reduced cytotoxicity, apoptosis, and oxidative stress while restoring mitochondrial function. In APP/PS1 transgenic mice, Tub administration improved cognitive performance, reduced amyloid-β plaque deposition, attenuated microglial activation, and attenuated neuronal loss, with efficacy superior to donepezil. Mechanistically, Tub selectively inhibited p38 MAPK phosphorylation without affecting ERK or JNK pathways, as confirmed by pharmacological inhibition and activation experiments. These findings identify Tub as a promising multi-target natural compound for AD intervention through p38 MAPK pathway modulation.

PMID:
42495541
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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