Neurotrophic effect of citrus auraptene: neuritogenic activity in PC12 cells

• Published in: International journal of molecular sciences Vol. 13; no. 5; pp. 5338 - 5347
• Main Authors: Furukawa, Yoshiko, Watanabe, Sono, Okuyama, Satoshi, Nakajima, Mitsunari
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2012; Molecular Diversity Preservation International (MDPI)
• Subjects: Animals; auraptene; Axonogenesis; Cell proliferation; Cells, Cultured; Citrus - chemistry; Citrus fruits; Citrus grandis; Cortex; Coumarin; Coumarins - chemistry; Coumarins - pharmacology; Differentiation; Enzyme Activation - drug effects; ERK1/2; Extracellular signal-regulated kinase; Kinases; Learning; Long term memory; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Monoterpenes; n-Hexane; neurite outgrowth; Neurites - drug effects; Neurites - metabolism; Neurogenesis - drug effects; neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; PC12 Cells; Penicillin; Pheochromocytoma cells; Phosphorylation; Proteins; Rats; Rats, Wistar; Signal transduction; United States > US; Japan; Citrus grandis; auraptene; ERK1/2; neurite outgrowth; neurons; PC12 cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms13055338

The activation of extracellular signal-regulated kinases (ERK) leads to a number of cellular changes associated with the development of long-term memory. Using cultured cortical neurons, we previously showed that the n-hexane extract prepared from the peels of Citrus grandis (Kawachi bankan) induces the activation of ERK1/2 and that one of the compounds with this ability in the extract is 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), a Citrus polymethoxyflavone. In fact, we found that HMF has the ability to rescue mice from drug-induced learning impairment. This hexane extract contains auraptene (AUR), a coumarin derivative with a monoterpene unit, together with HMF. The present study was designed to investigate the effect of AUR in vitro. Our results show that 1) AUR had the ability to induce the activation of ERK1/2 in not only cortical neurons but also the rat pheochromocytoma cell line (PC12 cells), which is a model system for studies on neuronal proliferation and differentiation; and 2) AUR had the ability to promote neurite outgrowth from PC12 cells.