Protective Effects of Caffeic Acid and the Alzheimer's Brain: An Update

Background: Caffeic acid (CA) and related phenylpropanoic acids are ubiquitous natural products of the shikimic acid pathway origin. Due to the presence of diorthohydroxyl aromatic (catecholic) moiety, CA is not only one of the most potent antioxidant phenyl propanoids but also displays numerous other pharmacological effects ranging from antiinflammatory to anticancer effects. Objective: Recent studies also demonstrated that CA both in its free form or conjugated with other groups such as quinic acid and sugars displays profound effects in the brain including protection from toxicity induced by a variety of agents and/or experimental models of Alzheimer's disease (AD). In this communication, the anti-AD therapeutic potential of CA and its two most common conjugated natural bioactive derivatives, chlorogenic acid (CGA) and caffeic acid phenethyl ester (CAPE), is scrutinised by reviewing literature in the past ten years. Besides the common global antioxidant effects, specific antiinflammatory mechanisms in the brain along with the various processes of beta-amyloid formation, aggregation and neurotoxicity targets are discussed. Conclusion: The mini-review also provides an insight into enhancing the therapeutic potential of existing anti-AD drugs by incorporating a CA structural moiety.