News
17 July, 2001
TAKARA's scientists discover compounds enhancing in vivo production of Nerve Growth Factor

Scientists at the Biomedical Group of TAKARA Shuzo Co Ltd have discovered that in vivo production of Nerve Growth Factor (NGF) is enhanced by several compounds which are contained in edible, perennial plants such as Ashitaba (Angelica keiskei Koidzumi), hops (Humulus luplus), edible flowers of chrysanthemum, and Gajutsu (Curcuma zedoaria Roscoe, one strain of turmeric). The Biomedical Group has already filed patents for these discovery and compounds, and these research results will be presented at scientific meetings held in August and the fall.

NGF is a biological substance which is essential in the development and survival of certain neurons in both the central and peripheral nervous systems. So, this protein is expected to be effective in preventing and treating Alzheimer-type dementia and diabetic peripheral neuropathy. However, it is difficult to use NGF itself as a therapeutic agent, due to the high molecular. Consequently, pharmaceutical and biotechnology companies seek NGF-production enhancers which can pass through the blood-brain barrier to work in the brain of concern. Until now, a variety of small molecular enhancers have been found, but there is no compound to be developed as a drug because of their cytotoxic effect or narrow range of effective doses.

Eight compounds with activity to enhance NGF production
Extracts of the edible plants were assayed for the biological activity to stimulate NGF production by measuring amounts of NGF produced by a mouse fibroblast cell line. Using this assay system, the scientists found that extracts of Ashitaba, hops, edible flowers of chrysanthemum, and Gajutsu showed the high activity in enhancement of NGF production. Further, active constituents were isolated from the extracts and then their molecular structures were determined. Four coumarin compounds including two novel ones and one chroman compound were identified in the extract from Ashitaba. A xanthohumol compound, one of chalcones, was identified in the extract of hops. Furthermore, two sesquiterpenoid compounds were also identified in edible flowers of chrysanthemum.

Although beer contains hops as an ingredient, most of xanthohumol in hops is converted into iso-xanthohumol, that is inactive in enhancement of NGF production, during brewing. The compounds TAKARA found show the activity in a wide range of doses, indicating a superior property to compounds previously reported.

Enhancement of NGF production by orally taken substances
In vivo activity of xanthohumol from hops and dry powders of Ashitaba was examined in rats by oral administration. Contents of NGF in the submandibular gland, the brain and/or the gastrocnemial muscle were compared after four days of oral administration.

Xanthohumol was orally given once daily for four days at the dose of 3 mg/kg of body weight. NGF content in the gland was more than 80-fold higher in the treated group than in the control. Furthermore, the scientists observed as high as 20% increase of NGF contents in the brain of rats orally given xanthohumol.

Rats were fed by diet containing 1% Ashitaba dry powders (estimated dose: 750 mg/kg/day) for four days. The rats showed as high as about 20% increase of NGF concentration in the gastrocnemial muscle compared to animals given a normal diet.

As mentioned above, the scientists have demonstrated the possibility that dementia and peripheral neuropathy can be prevented by daily taking the medicinal food such as Ashitaba and hops. Especially, it seems to be of greater interest that NGF content in the brain was increased by oral administration of xanthohumol. The Biomedical Group has already filed patents for these discovery and compounds.

Development of medicinal foods by the Biomedical Group
Both improvement of QOL (quality of life) and reduction of health care costs are major concerns in an aging society. Especially, longevity with healthier lives is most important. TAKARA Biomedical Group has a clear conception that "Let your food be your medicine" (by Hippocrates, the Father of Medicine), and has been establishing substantial R & D pipelines of medicinal foods, showing biological activities to keep healthier lives. For example, researches on oligosaccharides from seaweed have been performed to discover their medicinal activities for 12 years. Until now, kombu-fucoidan and agaro-oligosaccharide from agar are originally developed as a medicinal diet upon many research findings. Present results will generate another dietary product, in near future, which may promote healthier lives without any neuronal defects.

This article is translated from the press release in Japanese for your convenience.


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