2. Academic Validation
  3. Da-Bu-Yin-Wan rescues cognitive deficits in aging and Alzheimer's disease models by Wnt/β-catenin-dependent restoration of lysosomal acidification

Da-Bu-Yin-Wan rescues cognitive deficits in aging and Alzheimer's disease models by Wnt/β-catenin-dependent restoration of lysosomal acidification

  • Phytomedicine. 2026 Apr:153:157916. doi: 10.1016/j.phymed.2026.157916.
Haijun Zhang 1,  Hao Zhang 1,  Meihuan Zhao 1,  Wenjun Luo 1,  Simin Chen 1,  Ping Wang 2,  Xiao Liu 3,  Shijun Xu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 2 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: [email protected].
PMID: 41662806 DOI: 10.1016/j.phymed.2026.157916
Abstract

Background: Lysosomal acidification deficits are increasingly recognized as a convergent pathological mechanism driving both age-related cognitive decline (ARCD) and early Alzheimer's disease (AD) progression, creating a self-reinforcing cycle of cellular aging and Aβ dyshomeostasis. Despite demonstrated neuroprotective effects of Da-Bu-Yin-Wan (DBYW) in Parkinson's disease models, its therapeutic potential for lysosomal dysfunction in ARCD and AD remains an uncharted area of investigation.

Purpose: This present work aimed to elucidate the mechanistic basis by which DBYW mitigates both ARCD and AD pathology through functionally rescuing impaired lysosomal acidification.

Methods: Cell-based D-galactose and Aβ-induced in BV2 cells to study lysosomal acidification. Molecular analyses combined immunofluorescence localization studies with quantitative immunoblotting of lysosomal and Wnt signaling proteins. In vivo, DBYW treatment effects were systematically evaluated in both D-gal-induced and APP/PS1 transgenic models using cognitive behavioral followed by immunohistochemical and biochemical assessment of brain tissues lysosomal parameters and Wnt signaling activity.

Results: DBYW attenuated the mechanistic basis of ARCD and AD pathology by functionally rescuing impaired lysosomal acidification. Overexpression of β-catenin could modulate D-galactose or Aβ-induced dysregulation of the Wnt/β-catenin pathway and restore lysosomes with abnormal acidification, while DBYW could regulate lysosomal function by promoting Wnt/β-catenin signaling. In addition, in D-gal-induced aging and AD model mice, DBYW treatment activated Wnt/β-catenin signaling to restore lysosomal acidification, while spatial memory deficits in ARCD and AD models were improved, and pathology in mouse attenuation and APP/PS1 mouse brain tissue was inhibited.

Conclusion: DBYW shows a potential dual efficacy in improving cognitive decline in ARCD and AD models. It makes DBYW a promising disease-modifying intervention targeting the shared lysosomal pathophysiology of aging-associated neurodegeneration.

Keywords

Age-related cognitive decline; Alzheimer’s disease; Da-Bu-Yin-Wan; Lysosomal acidification; Wnt/β-catenin signaling.

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