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Fujiwara H.,Tohoku University | Kogure A.,Tohoku University | Sakamoto M.,Tohoku University | Yamakuni T.,Tohoku University | And 9 more authors.
Journal of Pharmacological Sciences | Year: 2011

To prove the pharmacological actions of honeybee royal jelly (RJ) on the nervous system, we examined the effects of RJ on CRE-mediated transcription. RJ increased CRE-mediated transcription in PC12D cells. Moreover, CRE-mediated transcriptional activity by RJ was enhanced by nobiletin. U0126, a MEK inhibitor, inhibited CRE-mediated transcription by combining RJ plus nobiletin without affecting transcription by RJ alone. These results suggest that RJ stimulates CRE-mediated transcription via an ERK-independent cascade, whereas the increasing CRE-mediated transcriptional effect by nobiletin is dependent on ERK phosphorylation. Combining RJ plus nobiletin may activate effectively neuronal functions via enhancement of CRE-mediated transcription. © The Japanese Pharmacological Society.

Fujiwara H.,Tohoku University | Fujiwara H.,University of Toyama | Kimura J.,University of Shizuoka | Sakamoto M.,Tohoku University | And 9 more authors.
Canadian Journal of Physiology and Pharmacology | Year: 2014

Neprilysin (NEP) is one of the candidate amyloid β protein (Aβ) degrading enzymes affecting brain Aβ clearance. This enzyme declines in the brain with age, which leads to the increased Aβ deposition in Alzheimer's disease (AD). Pharmacological activation of NEP during the aging process, therefore, represents a potential strategy to prevent the development of AD. To examine the influence of nobiletin on neprilysin activity, we measured cellular NEP activity in SK-N-SH cells. Moreover, NEP expression was examined by using reverse transcription - polymerase chain reaction and Western blotting. Measurement of cellular NEP activity showed that nobiletin stimulated this in a dose- and time-dependent manner in SK-N-SH cells. Moreover, nobiletin increased the expression of NEP mRNA, and then the levels of NEP protein, also in a dose- and time-dependent manner. Our findings showed that nobiletin promoted NEP gene and protein expression, resulting in enhancement of cellular NEP activity in SK-N-SH cells. This compound could be a novel Aβ-degrading compound for use in the development of disease-modifying drugs to prevent and (or) cure AD.

Li C.,University of Ryukyus | Mannoor M.K.,University of Ryukyus | Toma N.,The University of Okinawa | Taniguchi T.,Niigata University | And 5 more authors.
Biomedical Research | Year: 2011

Prolonged excessive ingestion or consumption of alcohol eventually results in hepatic insuffi-ciency; induces the aggravation of viral hepatitis and/or fatty liver. The long term ingestion of alcohol not only induces a decline in the immune function but also promotes the produc-tion of inflammatory cytokines by Kupffer cells activated by enterobacterial endotoxins. Royal Jelly has numerous functions, such as for the maintenance of health, immunopotentia-tion and age-retarding etc. Furthermore, Royal Jelly functions as a potent immunomodula-tor, such as Royal Jelly ameliorates stress-associated immune dysfunction. An alcoholic he-patic insufficiency mouse model was constructed by feeding it a liquid diet containing 5 % ethanol and features of the innate immune system were observed to assess whether Royal Jelly has any effect on alcohol-induced liver insufficiency. The data reveal that Royal Jelly administration (1) exhibits prophylactic effect on alcohol-induced hepatomegaly and (2) functions in restoration of transaminase levels caused by impaired hepatocytes. Royal Jelly-modulated important immune phenomena on alcoholic liver injury include (1) activation of liver natural killer cells and (2) control of the levels of IL-4, IL-5, and TNF-alpha in the se-rum. These findings provide evidence that Royal Jelly might have the capacity to restore the function of the immune system in individuals with alcoholic liver diseases.

Loading Japan Royal Jelly JRJ Co. collaborators
Loading Japan Royal Jelly JRJ Co. collaborators