Skip to main content
Log in

Oroxylin A, a Flavonoid, Stimulates Adult Neurogenesis in the Hippocampal Dentate Gyrus Region of Mice

  • ORIGINAL PAPER
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Previously, we reported the cognitive enhancing effects of oroxylin A in unimpaired mice and its memory ameliorating activity in various memory impaired mice. To elucidate the mechanism mediating the cognitive effects of oroxylin A, this study examined the consequences of oroxylin A administration on neurogenesis in the hippocampal dentate gyrus using immunostaining for 5-bromo-2-deoxyuridine (BrdU) incorporation. In addition, we determined whether the new cells adopted a neuronal or glial fate by examining the co-localization of BrdU staining with neuronal or glial markers. Administration of oroxylin A in a dose-dependent and time-dependent manner increased the number of BrdU-incorporating cells. Moreover, the percentage of BrdU-incorporating cells co-localized with neuronal markers, neuronal nuclei, was significantly increased by the oroxylin A administration. These results suggest that the increased neurogenesis induced by the administration of oroxylin A could be, at least in part, associated with its positive effects on cognitive processing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Altman J (1962) Are new neurons formed in the brains of adult mammals? Science 135:1127–1128

    Article  CAS  PubMed  Google Scholar 

  2. Goings GE, Sahni V, Szele FG (2004) Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 996:213–226

    Article  CAS  PubMed  Google Scholar 

  3. Doetsch F (2003) The glial identity of neural stem cells. Nat Neurosci 6:1127–1134

    Article  CAS  PubMed  Google Scholar 

  4. Hagg T (2005) Molecular regulation of adult CNS neurogenesis: an integrated view. Trends Neurosci 28:589–595

    Article  CAS  PubMed  Google Scholar 

  5. Tomimori T, Miyaichi Y, Kizu H (1982) On the flavonoid constituents from the roots of Scutellaria baicalensis Georgi. I. Yakugaku Zasshi 102:388–391

    CAS  PubMed  Google Scholar 

  6. Go WJ, Ryu JH, Qiang F et al (2009) Evaluation of the flavonoid oroxylin A as an inhibitor of P-glycoprotein-mediated cellular efflux. J Nat Prod 72:1616–1619

    Article  CAS  PubMed  Google Scholar 

  7. Li HN, Nie FF, Liu W et al (2008) Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. Toxicology 257:80–85

    Article  PubMed  Google Scholar 

  8. Kim DH, Jeon SJ, Son KH et al (2006) Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice. Pharmacol Biochem Behav 85:658–668

    Article  CAS  PubMed  Google Scholar 

  9. Kim DH, Jeon SJ, Son KH et al (2007) The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice. Neurobiol Learn Mem 87:536–546

    Article  CAS  PubMed  Google Scholar 

  10. Kim DH, Kim S, Jeon SJ et al (2008) The effects of acute and repeated oroxylin A treatments on Ab(25–35)-induced memory impairment in mice. Neuropharmacology 55:639–647

    Article  CAS  PubMed  Google Scholar 

  11. Morgan D (2007) Amyloid, memory and neurogenesis. Exp Neurol 205:330–335

    Article  CAS  PubMed  Google Scholar 

  12. Gilbert ME, Kelly ME, Samsam TE et al (2005) Chronic developmental lead exposure reduces neurogenesis in adult rat hippocampus but does not impair spatial learning. Toxicol Sci 86:365–374

    Article  CAS  PubMed  Google Scholar 

  13. Sairanen M, Lucas G, Ernfors P et al (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25:1089–1094

    Article  CAS  PubMed  Google Scholar 

  14. Kronenberg G, Reuter K, Steiner B et al (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463

    Article  PubMed  Google Scholar 

  15. Lee S, Kim DH, Yoon SH et al (2009) Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus. Neurosci Lett 467:111–116

    Article  CAS  PubMed  Google Scholar 

  16. Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, San Diego, pp 74–118

    Google Scholar 

  17. West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497

    Article  CAS  PubMed  Google Scholar 

  18. Lee J, Seroogy KB, Mattson MP (2002) Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem 80:539–547

    Article  CAS  PubMed  Google Scholar 

  19. Kempermann G, Gast D, Kronenberg G et al (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130:391–399

    Article  CAS  PubMed  Google Scholar 

  20. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  CAS  PubMed  Google Scholar 

  21. Drew MR, Hen R (2007) Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurol Disord Drug Targets 6:205–218

    Article  CAS  PubMed  Google Scholar 

  22. Luo C, Xu H, Li XM (2005) Quetiapine reverses the suppression of hippocampal neurogenesis caused by repeated restraint stress. Brain Res 1063:32–39

    Article  CAS  PubMed  Google Scholar 

  23. Tchantchou F, Lacor PN, Cao Z et al (2009) Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis 18:787–793

    CAS  PubMed  Google Scholar 

  24. Ajmone-Cat MA, Iosif RE, Ekdahl CT et al (2006) Prostaglandin E2 and BDNF levels in rat hippocampus are negatively correlated with status epilepticus severity: no impact on survival of seizure-generated neurons. Neurobiol Dis 23:23–35

    Article  CAS  PubMed  Google Scholar 

  25. Nakagawa S, Kim JE, Lee R et al (2002) Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein. J Neurosci 22:3673–3682

    CAS  PubMed  Google Scholar 

  26. Walton M, Woodgate AM, Muravlev A et al (1999) CREB phosphorylation promotes nerve cell survival. J Neurochem 73:1836–1842

    CAS  PubMed  Google Scholar 

  27. Nakamichi N, Takarada T, Yoneda Y (2009) Neurogenesis mediated by g-aminobutyric acid and glutamate signaling. J Pharmacol Sci 110:133–149

    Article  CAS  PubMed  Google Scholar 

  28. Keller EA, Zamparini A, Borodinsky LN et al (2004) Role of allopregnanolone on cerebellar granule cells neurogenesis. Dev Brain Res 153:13–17

    Article  CAS  Google Scholar 

  29. Mayo W, Lemaire V, Malaterre J et al (2005) Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus. Neurobiol Aging 26:103–114

    Article  CAS  PubMed  Google Scholar 

  30. Tozuka Y, Fukuda S, Namba T et al (2005) GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 47:803–815

    Article  CAS  PubMed  Google Scholar 

  31. Nilsson M, Perfilieva E, Johansson U et al (1999) Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol 39:569–578

    Article  CAS  PubMed  Google Scholar 

  32. Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375

    Article  CAS  PubMed  Google Scholar 

  33. Clelland CD, Choi M, Romberg C et al (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213

    Article  CAS  PubMed  Google Scholar 

  34. Neri M, Maderna C, Ferrari D et al (2010) Robust generation of oligodendrocyte progenitors from human neural stem cells and engraftment in experimental demyelination models in mice. PLoS One 5:e10145

    Article  PubMed  Google Scholar 

  35. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494

    Article  CAS  PubMed  Google Scholar 

  36. Eriksson PS, Wallin L (2004) Functional consequences of stress-related suppression of adult hippocampal neurogenesis—a novel hypothesis on the neurobiology of burnout. Acta Neurol Scand 110:275–280

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a grant funded by Korean Food and Drug Administration (2005; L-05-03-2-CHM-628-B).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jong Hoon Ryu.

Additional information

Present name: The name of Seungjoo Lee was legally changed into Seungheon Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, S., Kim, D.H., Lee, D.H. et al. Oroxylin A, a Flavonoid, Stimulates Adult Neurogenesis in the Hippocampal Dentate Gyrus Region of Mice. Neurochem Res 35, 1725–1732 (2010). https://doi.org/10.1007/s11064-010-0235-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-010-0235-y

Keywords

Navigation