Combined Treatment with Two Water Extracts of Eleutherococcus senticosus Leaf and Rhizome of Drynaria fortunei Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind Study in Healthy Adults

Nutrients. 2020 Jan 23;12(2):303. doi: 10.3390/nu12020303.


We previously found that the water extract of Eleutherococcus senticosus leaves (ES extract) enhanced cognitive function in normal mice. Our study also revealed that the water extract of rhizomes of Drynaria fortunei (DR extract) enhanced memory function in Alzheimer's disease model mice. In addition, our previous experiments suggested that a combined treatment of ES and DR extracts synergistically improved memory and anti-stress response in mice. Although those two botanical extracts are expected to be beneficial for neuropsychological function, no clinical data has ever been reported. Therefore, we performed a placebo-controlled, randomized, double-blind study to evaluate cognitive enhancement and anti-stress effects by the intake of a combined extract in healthy volunteers. The intake period was 12 weeks. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment. The combined treatment of ES and DR extracts significantly increased the figure recall subscore of RBANS (p = 0.045) in an intergroup comparison. Potentiation of language domain ((p = 0.040), semantic fluency (p = 0.021) and figure recall (p = 0.052) was shown by the extracts (in intragroup comparison). In anti-stress response, the anxiety/uncertainly score was improved by the extract in an intragroup comparison (p = 0.022). No adverse effects were observed. The combined treatment of ES and DR extracts appear to safely enhance a part of cognitive function in healthy adults.

Keywords: Drynaria fortunei rhozomes; Eleutherococcus senticosus leaves; Healthy subject; anti-stress; cognitive function.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cognition / drug effects*
  • Double-Blind Method
  • Eleutherococcus* / chemistry
  • Female
  • Healthy Volunteers
  • Humans
  • Japan
  • Male
  • Mental Recall / drug effects
  • Middle Aged
  • Nootropic Agents / administration & dosage*
  • Nootropic Agents / isolation & purification
  • Plant Extracts / administration & dosage*
  • Plant Extracts / isolation & purification
  • Plant Leaves
  • Polypodiaceae* / chemistry
  • Rhizome
  • Solvents / chemistry
  • Water / chemistry


  • Nootropic Agents
  • Plant Extracts
  • Solvents
  • Water