Apple Peel and Flesh Contain Pro-neurogenic Compounds

Research output: Contribution to journalResearch articleContributedpeer-review


  • Muhammad Ichwan - , Center for Regenerative Therapies Dresden (CRTD) (Author)
  • Tara L Walker - , University of Queensland (Author)
  • Zeina Nicola - , Center for Regenerative Therapies Dresden (Author)
  • Jutta Ludwig-Müller - , Chair of Plant Physiology (Author)
  • Christoph Böttcher - , Leibniz Institute of Plant Biochemistry (Author)
  • Rupert W Overall - , Center for Regenerative Therapies Dresden (CRTD) (Author)
  • Vijay S Adusumilli - , Center for Regenerative Therapies Dresden (Author)
  • Merve Bulut - , Center for Regenerative Therapies Dresden (CRTD) (Author)
  • Alex M Sykes - , Griffith University Queensland (Author)
  • Norbert Hübner - , Max Delbrück Center for Molecular Medicine (MDC) (Author)
  • Gerardo Ramirez-Rodriguez - , National Institute of Psychiatry "Ramon de laFuente Muñiz (Author)
  • Leonardo Ortiz-López - , National Institute of Psychiatry "Ramon de laFuente Muñiz (Author)
  • Enrique A Lugo-Hernández - , National Institute of Psychiatry "Ramon de laFuente Muñiz (Author)
  • Gerd Kempermann - , Center for Regenerative Therapies Dresden (Author)


As mammals evolved with exposure to particular diets, naturally abundant compounds may have become part of the set of environmental co-determinants that shaped brain structure and function. Here we investigated whether bioactive factors found in apples directly affect hippocampal neurogenesis in the adult mouse. We found that quercetin, the most abundant flavanol in apple peel, was anti-proliferative at high concentrations but pro-neurogenic at low concentrations. This was confirmed in vivo, with intraperitoneally delivered quercetin promoting survival and neuronal differentiation, without affecting proliferation. Using a bioassay-guided fractionation approach we also identified additional pro-neurogenic compounds in apple flesh that were not related to flavonoids. We found that 3,5-dihydroxybenzoic acid significantly increased neural precursor cell proliferation and neurogenesis. This work shows that both flavonoids and 3,5-dihydroxybenzoic acid are pro-neurogenic, not only by activating precursor cell proliferation but also by promoting cell-cycle exit, cellular survival, and neuronal differentiation.


Original languageEnglish
Pages (from-to)548-565
Number of pages18
JournalStem cell reports
Issue number3
Publication statusPublished - 9 Mar 2021

External IDs

PubMedCentral PMC7940132
Scopus 85101703528
ORCID /0000-0002-5304-4061/work/142238779



  • Animals, Antioxidants/pharmacology, Cell Cycle/drug effects, Cell Differentiation/drug effects, Cell Proliferation/drug effects, Cell Survival/drug effects, Female, Flavonoids/pharmacology, Fruit/chemistry, Hippocampus/drug effects, Hydroxybenzoates/pharmacology, Male, Malus/chemistry, Mice, Mice, Inbred C57BL, Neurogenesis/drug effects, Proto-Oncogene Proteins c-akt/metabolism, Quercetin/pharmacology, Receptors, G-Protein-Coupled/metabolism, Resorcinols/pharmacology, Signal Transduction