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Ota H.,University of Tokyo | Akishita M.,University of Tokyo | Tani H.,Yamada Bee Company | Tatefuji T.,Yamada Bee Company | And 5 more authors.
Journal of Natural Products | Year: 2013

Gnetum gnemon is an arboreal dioecious plant that is cultivated in Indonesia. The seeds of this species mainly contain dimeric stilbenoid compounds [gnetin C (1), gnemonoside A (2), and gnemonoside D (3)] along with trans-resveratrol (4). trans-Resveratrol has been reported to have antiaging, anticancer, and antidiabetic effects, as well as being a calorie restriction mimetic. SIRT1 exerts a protective effect against vascular senescence. In this study, the effects of these four main stilbenoid derivatives of a G. gnemon seed endosperm ethanolic extract on endothelial senescence were investigated. In streptozotocin-induced diabetic mice, administration of the G. gnemon ethanolic extract increased SIRT1 and decreased endothelial senescence. The concentration of 1 in blood plasma was 6-fold higher than 4 in these mice. Next, the in vitro effects of the four main stilbenoid derivatives of G. gnemon seeds were investigated. Senescent human umbilical vein endothelial cells were induced by hydrogen peroxide. Endothelial senescence was inhibited by 4, which increased the expression of endothelial nitric oxide synthase and SIRT1, whereas 1-3 had no effect. These results indicated that the ethanolic extract of G. gnemon seeds inhibits endothelial senescence, suggesting that 4 plays a critical role in the prevention of endothelial senescence. © 2013 The American Chemical Society and American Society of Pharmacognosy.

Aoki M.,Gifu University | Ohkuma A.,Analysis Inc. | Fukushima S.,Yamada Bee Company | Tatefuji T.,Yamada Bee Company | Tatefuji T.,Analysis Inc.
Japanese Pharmacology and Therapeutics | Year: 2015

Objectives: Tinnitus interferes with the quality of life, however no drug has been effective in reducing the magnitude of tinnitus. We investigated whether lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine can provide a therapeutic effect for mild tinnitus. Methods: Sixty subjects with mild self-perceived tinnitus handicap participated in a doubleblind, placebo-controlled trial using lyophilized powder of enzymolyzed honeybee larvae combined with γ-aminobutyric acid, Riboflavin and Cyanocobalamin (honeybee larvae group) or placebo (placebo group). A visual analog scale (VAS) to rate the severity of tinnitus (loudness, duration and frequency), the Tinnitus Handicap Inventory (THI) and Chalder fatigue scale (CFS) were measured upon entry into the study and after 12 weeks of follow-up. Results: Total VAS score to rate the severity of self-perceived tinnitus (loudness, duration, frequency, and annoyance) was significantly improved by 12-week intervention in honeybee larvae group (P<0.05),and the score on the THI was reduced by 12-week intervention in both groups (P<0.05). The intervention with honeybee larvae tended to decrease total CFS score, especially physical component score of the CFS (P=0.06). The change ratio of the total VAS score by the intervention significantly correlated with the change ratio of the CFS in honeybee group (r=0.54, P<0.05). Conclusion: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represent an effective complementary medicine for subjects with mild self-perceived tinnitus handicap.

Disclosed are: a lactic acid bacterium belonging to

Tani H.,Yamada Bee Company | Hikami S.,Yamada Bee Company | Iizuna S.,Yamada Bee Company | Yoshimatsu M.,Yamada Bee Company | And 6 more authors.
Journal of Agricultural and Food Chemistry | Year: 2014

Fruits and seeds of melinjo (Gnetum gnemon L.) are resveratrol derivative-rich materials. Pharmacokinetics of resveratrol derivatives in healthy volunteers after oral administration of 1000 mg of melinjo seed extract (MSE) powder were assessed and compared with those after oral dosing of trans-resveratrol (tRV) powder containing 4.8 mg of tRV only, equivalent to the content in 1000 mg MSE powder. Plasma tRV concentrations with enzymatic hydrolysis were maintained over 24 h, with a tmax of 12 h and a mean residence time (MRT) of 14 h, 5 and 2 times higher than those for tRV powder intake, respectively. Gnetin C, a resveratrol dimer, with hydrolysis was maintained in plasma for >96 h with a 36 h MRT. With repeated doses once daily for 28 days, plasma tRV and gnetin C concentrations with hydrolysis were in good agreement with the theoretical curves. MSE powder was well tolerated up to the oral dosing of 5000 mg with no serious adverse events. © 2014 American Chemical Society.

Yamaki A.,Yamada Bee Company | Kimura Y.,Yamada Bee Company | Sado T.,Yamada Bee Company | Hashimoto K.,Yamada Bee Company | Kajimoto O.,Osaka City University
Japanese Pharmacology and Therapeutics | Year: 2015

Objective: The aim of this study was to evaluate the effect of bilberry, lutein and brazilian propolis contain diet (BLP) intake on eye fatigue in healthy adults. Methods: Six men, six women ranging in age from 32 to 57 with eye fatigue were participated in this randomized controlled trial for 2 weeks. They ingested three capsules containing 270 mg bilberry extract, 9 mg lutein, 75 mg brazilian propolis ethanol extract, or placebo every day. Before and after ingestion, and VDT operation, we conduct VAS (visual analogue scale) test, Jikaku-sho Shirabe, Schirmer test, and autonomic function by the acceleration pulse wave. Results: Eye fatigue symptoms such as "eye fatigue", "dry eye", "listlessness" were significantly improved in the active group after two weeks ingestion. And parasympathetic function (High Frequency: HF) was higher in active group than placebo group. Conclusions: The result of current study suggests that the BLP is suggested to improve eye fatigue and to alleviate disturbance in the balance of autonomic function.

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