Mechanisms of Traditional Chinese Medicine-Derived Active Components in the Treatment of Alzheimer's Disease: A Comprehensive Review.

Authors

Yu Tian, Jiageng Guo, Xinyue Lin, Fan Zhang, Jinling Xie, Xiaotao Hou, Jiagang Deng, Erwei Hao, Zhengcai Du

Published in

Journal of ethnopharmacology. Pages 122574. Oct 26, 2026. Epub Oct 26, 2026.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and multifactorial pathology. Because AD involves interacting pathological processes, the limited efficacy of conventional single-target therapies has increased interest in traditional Chinese medicine (TCM) and other natural medicines with multi-target pharmacological actions. TCM-derived active components originate from medicinal materials used in traditional practice and are evaluated using modern pharmacological approaches. Their source medicines have diverse traditional-use backgrounds. Some have historical associations with memory or cognitive symptoms, whereas many others were traditionally used for broader deficiency, phlegm, blood-stasis, heat, or related syndromic patterns. These records provide ethnopharmacological context for the source medicines but should not be taken as historical evidence for the anti-AD activity of their isolated constituents.
This review synthesizes current evidence on the mechanisms of TCM-derived bioactive components in AD while incorporating relevant traditional-use information on their source medicines. Particular attention is given to their multi-target actions and emerging mechanisms involving ferroptosis, mitophagy, and the gut-brain axis.
Mechanistic literature published between January 2019 and November 2025 was retrieved from Ovid MEDLINE, PubMed, ScienceDirect, and Web of Science. Ovid MEDLINE and PubMed were searched separately to maximize retrieval across indexed and additional PubMed records, with overlapping records removed during deduplication. Traditional-use information was evaluated separately for the source medicines. A targeted search of PubMed and ClinicalTrials.gov was also conducted to assess human interventional evidence for compounds covered in the review, with trial-registration information updated through August 2026.
Current preclinical findings suggest that TCM active components may produce coordinated preclinical pharmacological effects through multiple pathways, including the inhibition of β-amyloid (Aβ) production and deposition, regulation of tau aggregation and phosphorylation, alleviation of neuroinflammation and oxidative stress, improvement of mitophagy and iron metabolism disorders, and modulation of gut microbiota homeostasis. Among these components, saponins show broad mechanistic coverage. Flavonoids, polysaccharides, and other bioactive substances have likewise shown anti-inflammatory and antioxidant activities, together with protective effects on synaptic function, in preclinical models. These mechanistic findings were derived predominantly from cellular and animal studies, with computational analyses providing mainly hypothesis-generating support. Human evidence was available for only a small subset of compounds and was not uniformly positive. Huperzine A has progressed to controlled clinical testing but has shown mixed efficacy findings; resveratrol demonstrated CNS exposure and biomarker activity without consistent cognitive benefit; curcumin did not show efficacy in a placebo-controlled AD trial; and favorable signals from ginseng studies were limited by open-label designs and the use of whole preparations rather than isolated ginsenosides.
The available evidence supports broad preclinical activity of TCM-derived components across several interconnected AD-related processes, but the strength of mechanistic support varies markedly among compounds and pathways. Human translation remains limited and inconsistent, and current clinical data do not establish disease-modifying efficacy for the compounds reviewed. Further development should therefore be guided by the main uncertainty surrounding each candidate-whether mechanistic causality, reproducibility, systemic or CNS exposure, preparation standardization, or clinical efficacy-rather than by a fixed sequence of technologies.

PMID:
42933739
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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