Screening of β-secretase and acetylcholinesterase inhibitors from plant resources

J Nat Med. 2015 Jan;69(1):123-9. doi: 10.1007/s11418-014-0859-3. Epub 2014 Aug 15.

Abstract

The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of β-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.

MeSH terms

  • Acetylcholinesterase
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Benzodioxoles / chemistry
  • Benzodioxoles / isolation & purification
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Curcuma / chemistry
  • Curcumin / analogs & derivatives
  • Curcumin / chemistry
  • Curcumin / isolation & purification
  • Diarylheptanoids
  • Murraya / chemistry
  • Piper nigrum / chemistry
  • Piperidines / chemistry
  • Piperidines / isolation & purification
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Polycyclic Sesquiterpenes
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / isolation & purification
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification

Substances

  • Alkaloids
  • Benzodioxoles
  • Cholinesterase Inhibitors
  • Diarylheptanoids
  • Piperidines
  • Plant Extracts
  • Polycyclic Sesquiterpenes
  • Polyunsaturated Alkamides
  • Sesquiterpenes
  • bisdemethoxycurcumin
  • turmeric extract
  • caryophyllene
  • Acetylcholinesterase
  • Amyloid Precursor Protein Secretases
  • Curcumin
  • caryophyllene oxide
  • piperine
  • demethoxycurcumin