Silymarin ameliorates memory deficits and neuropathological changes in mouse model of high-fat-diet-induced experimental dementia

Naunyn Schmiedebergs Arch Pharmacol. 2014 Aug;387(8):777-87. doi: 10.1007/s00210-014-0990-4. Epub 2014 May 28.


A huge body evidences suggest that obesity is the single great risk factor for the development of dementia. Recently, silymarin, a flavonoid, clinically in use as a hepatoprotectant, has been reported to prevent amyloid beta-induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, its potential in high-fat-diet (HFD)-induced dementia has not yet been investigated. Therefore, the present study is designed to explore the role of silymarin in HFD-induced experimental dementia in mice. Morris water maze test was employed to assess learning and memory. Various biochemical estimations including brain acetylcholinerstarse activity (AchE), thiobarbituric acid-reactive species (TBARS) level, reduced glutathione level (GSH), nirate/nitrite, and myeloperoxidase (MPO) activity were measured. Serum cholesterol level was also determined. HFD significantly impaired the cognitive abilities, along with increasing brain AchE, TBARS, MPO, nitrate/nitrite, and serum cholesterol levels. Marked reduction of brain GSH levels was observed. On the contrary, silymarin significantly reversed HFD-induced cognitive deficits and the biochemical changes. The present study indicates strong potential of silymarin in HFD-induced experimental dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Cholesterol / blood
  • Dementia / drug therapy*
  • Dementia / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Female
  • Glutathione / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Mice
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nitrates / metabolism
  • Nitrites / metabolism
  • Peroxidase / metabolism
  • Silymarin / pharmacology
  • Silymarin / therapeutic use*
  • Thiobarbituric Acid Reactive Substances / metabolism


  • Neuroprotective Agents
  • Nitrates
  • Nitrites
  • Silymarin
  • Thiobarbituric Acid Reactive Substances
  • Cholesterol
  • Peroxidase
  • Acetylcholinesterase
  • Glutathione