Potentiation of nerve growth factor-action by picrosides I and II, natural iridoids, in PC12D cells

Ping Li, Kimihiro Matsunaga, Tohru Yamakuni, Yasushi Ohizumi

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


Natural iridoid, picroside I (β-D-glucopyranoside, 1a,1b,2,5a,6,6a- hexahydro-6-hydroxy-1a-(hydroxymethyl)oxireno[4,5]cyclopenta[1,2-c]pyran-2- yl, 6-(3-phenyl-2-propenoate)) or II (β-D-glucopyranoside, 1a,1b,2,5a,6,6a- hexahydro-6-[(4-hydroxy-3-methoxybenzoyl)oxy]-1a- (hydroxymethyl)oxireno[4,5]cyclopenta[1,2-c]pyran-2-yl) alone did not exhibit neuritogenic activity, but caused a concentration-dependent (>0.1 μM) enhancement of nerve growth factor (NGF, 2 ng/ml)-induced neurite outgrowth from PC12D cells. The picroside-induced enhancing action of NGF was abolished by GF109203X (2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3- yl)maleimide) (0.1 μM), a protein kinase C inhibitor. Furthermore, PD98059 (2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one) (20 μM), a potent mitogen-activated protein (MAP) kinase kinase inhibitor, completely blocked the picroside-induced enhancement of neurite outgrowth in the presence of NGF (2 ng/ml), suggesting that picrosides activate the MAP kinase-dependent signaling pathway. Interestingly, no increase in the expression of phosphorylated MAP kinase was observed in picroside-treated (60 μM) PC12D cells in the presence of NGF (2 ng/ml). These results suggest that picroside I or II enhances NGF-induced neurite outgrowth from PC12D cells, probably by amplifying a down-stream step of MAP kinase in the NGF receptor-mediated intracellular MAP kinase-dependent signaling pathway. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number2
Publication statusPublished - 2000 Oct 13
Externally publishedYes


  • Mitogen-activated protein (MAP) kinase
  • Nerve growth factor (NGF)
  • Neurite outgrowth activity
  • PC12D cell
  • Picroside I
  • Picroside II

ASJC Scopus subject areas

  • Pharmacology


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