Berberine in Alzheimer’s disease: from TCM pharmacology to translational barriers and multi-target therapeutic development
Year: 2026
Type: article
Abstract: Background Alzheimer's disease (AD) remains the most common cause of dementia and constitutes a major therapeutic challenge, since the current treatment methods offer minimal symptom relief and the available disease-modifying therapies have only moderate effects on certain patients and necessitate proper patient selection and monitoring. Growing awareness of AD as a multifactorial network disease involving accumulation of amyloid-β peptides, neurofibrillary tangles, neuroinflammation, oxidative stress, mitochondrial dysfunction, metabolic disorders, vascular pathology, and disturbances in the gut-brain axis has resulted in a growing interest in multi-target therapy approaches. Among natural drugs, berberine, a protoberberine alkaloid extracted mainly from Coptis chinensis, Phellodendron amurense, and Berberis plants, has become one of the most studied due to its rich pharmacological properties and traditional use in Traditional Chinese Medicine (TCM). Objective The review presents an integrated account of berberine from its historical use in classical Chinese medicine to its current development as a potential multi-target drug for AD. Methods We conducted a critical literature review in PubMed, Scopus, and Web of Science on the historical, pharmacological, mechanistic, preclinical, computational, and translational aspects of berberine and AD. Key Findings This review evaluates mechanistic, computational, pharmacokinetic, preclinical, pharmaceutical, and clinical evidence, paying particular attention to the relationship between target validation, drug exposure, and clinical translation. This review highlights translational challenges, including poor oral absorption, limited blood-brain barrier permeability, drug development hurdles, nanomedicine limitations, biomarker-driven clinical gaps, and regulatory barriers. Overall, evidence supports biological plausibility and preclinical activity, although its clinical effectiveness remains unproven. Conclusion Future efforts should focus on standardizing formulations, optimizing PK/PD, validating targets based on achievable exposure levels, conducting biomarker-driven clinical trials, and ensuring appropriate regulation. This review provides an evidence-based framework that integrates traditional wisdom and pharmacological knowledge into translational neuroscience to advance berberine as a potential multi-target therapy for AD.
Authors: Vikrant Verma, Charu Saxena
Institution: Swami Vivekanand Subharti University
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,550
OpenAlex ID: W7221779787