Honokiol improves learning and memory impairments induced by scopolamine in mice

Eur J Pharmacol. 2015 Aug 5;760:88-95. doi: 10.1016/j.ejphar.2015.04.013. Epub 2015 Apr 23.


Honokiol, a lignan isolated from the bark of Magnolia officinalis, has been reported to ameliorate the learning and memory impairments in senesed (SAMP8) mice. However, whether honokiol could improve scopolamine (SCOP)-induced learning and memory deficits in mice is still unknown. In this study, we aimed to investigate whether honokiol could reverse the SCOP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. Mice were given daily intraperitoneal injection of honokiol (10 and 20mg/kg) for 21 consecutive days. The results showed that honokiol significantly improved spatial learning and memory function (as assessed by the Morris water maze test) in the SCOP-treated mice. In addition, treatment with honokiol significantly decreased the protein and mRNA levels of interleukin (IL)-1β and the activity of acetylcholinesterase (AChE), while significantly increased the protein and mRNA levels of IL-10, and the level of acetylcholine (Ach) in the brain of the SCOP-treated mice. Moreover, honokiol also significantly suppressed the production of prostaglandin E 2 (PGE2) and mRNA expression of cyclooxygenase-2 (COX-2) in the brain of the SCOP-treated mice. Mechanistic investigations revealed that honokiol could markedly reverse the amount of phosphorylated Akt and extracellular regulated kinases 1/2 (ERK1/2) changes in the brain of the SCOP-treated mice. These results amply demonstrated that honokiol could improve learning and memory impairments induced by SCOP in mice, and the protective action may be mediated, at least in part, by inhibition of AChE activity, and amelioration of the neuroinflammatory processes in the SCOP-treated mice.

Keywords: Acetylcholinesterase; Acetylthiocholine iodide (PubChem CID: 74629); Dithiobisnitrobenzoic acid (PubChem CID: 6254); Donepezil hydrochloride (PubChem CID: 5741); Ferric chloride (PubChem CID: 24380); Honokiol; Honokiol (PubChem CID: 72303); Hydrochloride acid (PubChem CID: 313); Hydroxylamine hydrochloride (PubChem CID: 443297); Indomethacin (PubChem CID: 3715); Learning and memory impairments; Mice; Neuroinflammation; Scopolamine; Scopolamine (PubChem CID: 5184); Sodium hydroxide (PubChem CID: 14798); Trichloroacetic acid (PubChem CID: 6421).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Memory Disorders / chemically induced*
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Mice
  • Mice, Inbred ICR
  • Scopolamine / toxicity*


  • Biphenyl Compounds
  • Cholinesterase Inhibitors
  • Drugs, Chinese Herbal
  • Lignans
  • honokiol
  • Scopolamine