Neurite outgrowth of PC12 cells by 4'-O-ß-D-glucopyranosyl-3',4-dimethoxychalcone from Brassica rapa L. 'hidabeni' was enhanced by pretreatment with p38MAPK inhibitor.

ABSTRACT

The cellular effects of eleven compounds including chalcone glycosides isolated from Brassica rapa L. 'hidabeni' and their synthetic derivatives were studied in rat pheochromocytoma PC12 cells. Of the compounds tested, 4'-O-ß-D-glucopyranosyl-3',4-dimethoxychalcone (A2) significantly increased the levels of the phosphorylated forms of extracellular signal-regulated kinases 1/2 (ERK 1/2), p38 mitogen-activated protein kinase (p38MAPK), and stress-activated protein kinases/Jun amino-terminal kinases (JNK/SAPK), but it did not affect Akt. Nerve growth factor (NGF), a well-known neurotrophic factor, increased the levels of phosphorylated ERK1/2, JNK/SAPK, and Akt but not p38MAPK, which may mediate marked neurite outgrowth. Signals evoked by A2 shared common characteristics with those induced by NGF; therefore, we evaluated the neuritogenic activity of A2 and found it induced only weak neurite outgrowth. However, this effect was enhanced by pre-treatment with a p38MAPK inhibitor, suggesting that the phosphorylation of p38MAPK down-regulated neurite outgrowth. From the results of this study, it was found that A2 in combination with a p38MAPK inhibitor can induce NGF-like effects. Hence, a combination of chalcone glycosides containing A2 and a p38MAPK inhibitor increases the likelihood that chalcone glycosides could be put to practical use in the form of drugs or alternative medicines to maintain neural health.