Curcuminoids and Novel Opportunities for the Treatment of Alzheimer's Disease: Which Molecules are Actually Effective?

Curr Mol Pharmacol. 2019;12(1):12-26. doi: 10.2174/1874467211666181012150847.

Abstract

Background: Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular, curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD. These controversies, including conflicting results of clinical trials, are thought to be related to bioavailability of curcuminoids, which is low unless it is enhanced by developing a special formulation. However, there is growing evidence suggesting that other reasons may be of even greater importance, but these avenues are less explored.

Objective: Review relevant literature, and analyze potential reasons for the controversial results.

Methodology: Recent in vitro and preclinical studies; clinical trials (without a limiting period) were searched in PubMed and Google Scholar.

Results: While recent in vitro and preclinical studies confirm the therapeutic potential of curcuminoids in the treatment of AD and cognitive dysfunctions, results of corresponding clinical trials remain rather controversial.

Conclusion: The controversial results obtained in the clinical trials may be in part due to particularities of the curcuminoid formulations other than bioavailability. Namely, it seems likely that the various formulations differ in terms of their minor turmeric constituent(s). We hypothesize that these distinctions may be of key importance for efficacy of the particular formulation in clinical trials. A testable approach addressing this hypothesis is suggested.

Keywords: Alzheimer disease; TRP channels; clinical trials; curcuminoids; ferulic acid; turmeric..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid Sensing Ion Channels / chemistry
  • Acid Sensing Ion Channels / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cholinesterases / chemistry
  • Cholinesterases / metabolism
  • Clinical Trials as Topic
  • Curcumin / metabolism
  • Curcumin / therapeutic use*
  • Humans
  • Insulin / metabolism
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / metabolism

Substances

  • Acid Sensing Ion Channels
  • Amyloid beta-Peptides
  • Insulin
  • Transient Receptor Potential Channels
  • Cholinesterases
  • Curcumin