Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice

Pharm Biol. 2016;54(6):1052-64. doi: 10.3109/13880209.2015.1101476. Epub 2015 Oct 29.


Context: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet.

Objective: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice.

Materials and methods: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver.

Results: In extract, vanillic (632.093 μg/g) and chlorogenic acids (555.0 μg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p < 0.01), increased memory retention (p < 0.01), reduced MDA levels (p < 0.05), and elevated SOD, GPx, and CAT activities (p < 0.05) compared with the d-galactose group.

Discussion and conclusion: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.

Keywords: Antioxidant; learning; memory retention; phenolic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Behavior, Animal / drug effects
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism
  • DNA Damage / drug effects
  • Galactose / toxicity
  • Male
  • Maze Learning / drug effects
  • Mice, Inbred BALB C
  • Morus / chemistry*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Plasmids


  • Antioxidants
  • Plant Extracts
  • Galactose