In the 1980s, the authors developed the
enzyme immunoassay (EIA) system for mouse
nerve growth factor (
NGF) to clarify its important physiological roles. Our EIA system was a new and powerful tool for measurement of extremely low levels of
NGF in vitro and in vivo, and it contributed to investigation into the regulatory mechanism of
NGF synthesis. After that, we demonstrated that the compounds with a low molecular weight, such as
4-methylcatechol, which elicit stimulatory activity toward
NGF synthesis, were useful and practical for therapeutic purposes; as
NGF has potent activity on neuronal degeneration in both the central nervous system (CNS) and the peripheral nervous system. Since 2008, we have been searching for and isolating neuroprotective component(s) from citrus peels. As a result, our study revealed that 1) 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) has neuroprotective ability in the CNS by inducing
brain-derived neurotrophic factor (
BDNF) and by suppressing
inflammation; 2)
auraptene (AUR) also has neuroprotective ability in the CNS by suppressing
inflammation and by probably inducing
neurotrophic factor(s). As the content of AUR in the peels of Kawachi Bankan is exceptionally high, 1) we found this peel
powder to exert
neuroprotective effects in the brain of various pathological model mice; 2) some of the AUR transited from the peel to the juice during the squeezing process to obtain the juice. Therefore, K. Bankan juice, which is enriched in AUR by adding peel
paste to the raw juice, was shown to be practical for suppression of
cognitive dysfunction of aged healthy volunteers.