Neuroprotective effects of berberine in animal models of Alzheimer's disease: a systematic review of pre-clinical studies

BMC Complement Altern Med. 2019 May 23;19(1):109. doi: 10.1186/s12906-019-2510-z.


Background: Berberine is an isoquinoline alkaloid extracted from various Berberis species which is widely used in East Asia for a wide range of symptoms. Recently, neuroprotective effects of berberine in Alzheimer's disease (AD) animal models are being extensively reported. So far, no clinical trial has been carried out on the neuroprotective effects of berberine. However, a review of the experimental data is needed before choosing berberine as a candidate drug for clinical experiments. We conducted a systematic review on AD rodent models to analyze the drug effects with minimal selection bias.

Methods: Five online literature databases were searched to find publications reporting studies of the effect of berberine treatment on animal models of AD. Up to March 2018, 15 papers were identified to describe the efficacy of berberine.

Results: The included 15 articles met our inclusion criteria with different quality ranging from 3 to 5. We analyzed data extracted from full texts with regard to pharmacological effects and potential anti-Alzheimer's properties. Our analysis revealed that in multiple memory defects animal models, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.

Conclusion: AD is likely to be a complex disease driven by multiple factors. Yet, many therapeutic strategies based on lowering β-amyloid have failed in clinical trials. This suggest that the threapy should not base on a single cause of Alzheimer's disease but rather a number of different pathways that lead to the disease. Overall we think that berberine can be a promising multipotent agent to combat Alzheimer's disease.

Keywords: Alzheimer’s disease; Animal models; Berberine; Dementia; Neuroprotection.

Publication types

  • Systematic Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / physiopathology
  • Animals
  • Berberine* / chemistry
  • Berberine* / pharmacology
  • Berberine* / therapeutic use
  • Disease Models, Animal
  • Mice
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Rats


  • Neuroprotective Agents
  • Berberine