A New Alkylamide with Odd-Chain Fatty Acid from Pericarps of Japanese Pepper (Zanthoxylum piperitum (L.) DC.)

Neural stem cells (NSCs) are pluripotent stem cells that can differentiate into neurons and glia cells. They continue to supply these cells throughout life in the adult central nervous system. However, it is revealed that differentiation capacity of NSCs has been to decrease with aging and mental stress. The decreasing capacity suspected to be associated with the development of neurodegenerative diseases and depression. Therefore, compounds that regulate the differentiation of NSCs into astrocytes may provide a good clue to understanding the role of astrocytes in maintaining brain function. In this study, the extracts of the pericarps of Japanese pepper (Zanthoxylum piperitum (L.) DC.), which has long been popular as a spice in Japanese cuisine, were subjected to solvent fractionation, purification and spectral analysis. As a result, an alkylamide with an unusual odd-chain fatty acid moiety, (2E)-N-isobutyltridec-2-enamide (1), was isolated along with three known alkylamides (2–4). All these alkylamides were evaluated for their promoting activity in the differentiation of mouse neural stem cells (mNSCs) into astrocyte. As the result, compounds 2 and 4 increased numbers of glial fibrillary acidic protein (GFAP)-positive cells in in vitro differentiation assays using mNSCs. These findings suggest the potential for new uses of Japanese pepper as a functional food that could be applied to the prevention and treatment of neurodegenerative diseases and depression.