Abstract: Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders. Among the samples tested, extracts prepared from the peels of Citrus grandis (Kawachi bankan) were found to have the greatest ability to activate ERK1/2. The active substances were isolated by chromatographic separation, and one of them was identified to be 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF). HMF significantly induced the phosphorylation of cAMP response element-binding protein (CREB), a downstream target of activated ERK1/2, which appears to be a critical step in the signaling cascade for the structural changes underlying the development of long-term potentiation (LTP). In addition, the administration of HMF into mice treated with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of spatial learning performance in the Morris mater-maze task. Taken together, these results suggest that HMF is a neurotrophic agent for treating patients with memory disorders.
Keywords: methoxyflavone; 3,5,6,7,8,3′,4′-heptamethoxyflavone; ERK1/2; Citrus grandis; Kawachi bankan; neurons; MK-801
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
MDPI and ACS Style
Furukawa, Y.; Okuyama, S.; Amakura, Y.; Watanabe, S.; Fukata, T.; Nakajima, M.; Yoshimura, M.; Yoshida, T. Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants. Int. J. Mol. Sci. 2012, 13, 1832-1845.
Furukawa Y, Okuyama S, Amakura Y, Watanabe S, Fukata T, Nakajima M, Yoshimura M, Yoshida T. Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants. International Journal of Molecular Sciences. 2012; 13(2):1832-1845.
Furukawa, Yoshiko; Okuyama, Satoshi; Amakura, Yoshiaki; Watanabe, Sono; Fukata, Takahiro; Nakajima, Mitsunari; Yoshimura, Morio; Yoshida, Takashi. 2012. "Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants." Int. J. Mol. Sci. 13, no. 2: 1832-1845.