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Encouraging Production of Nerve Growth Factor Inside The Body

Ashitaba, Angelica Keiskei Koidzumi, is a unique celery-like vegetable of Angelica family, indigenous to the Island of Hachijo in Japan. The plant is locally referred to as the "longevity herb" and its diverse biological activities for healthy lives have been scientifically reported. Leaves, stems and roots of Ashitaba contain a large amount of yellow substances, polyphenols called chalcones.  The Biomedical Group has performed researches on biological activities of Ashitaba, and found that the plant could stimulate the production of Nerve Growth Factor (NGF) inside the body (in vivo). . Thus, scientists of the Group have added a novel insight to physiological activities of Ashitaba, which was previously reported to show activities such as an immune system stimulation, healthy function of stomach and intestines, and anti-viral and anti-bacterial actions. Ashitaba is one of the few plants to have the ability to stimulate NGF. Ashitaba is also one of the few plants to produce B vitamins, which are normally produced in organic animal bodies.

Nerve growth factor (NGF) is the prototype for the neurotrophin family of polypeptides which are essential in the developments and survival of certain sympathetic and sensory neurons in both the central and peripheral nervous systems. NGF was discovered when mouse sarcoma tissue transplants in chicken embryos caused an increase in the size of spinal ganglia. In the course of attempting to characterise the agent responsible for this action, snake venom, employed as a phosphodiesterase, was found to be a rich source of NGF. An homologous tissue, the submaxillary gland of adult male mice, has become the preferred source of NGF; other unusually large concentrations are found in the guinea pig prostate gland and in bovine seminal plasma. The physiological relevance of these sources is not established. 

The NGF is synthesized in minute amounts in all vertebrate tissues, plays an essential role in the differentiation and survival of several nerve cell populations in the peripheral and central nervous system. The discovery of the NGF was defined by the Nobel Foundation as a milestone in developmental neurobiology.


Nerve Growth Factor and Alzheimers
From: Emily Maxfield
Date: 1/15/01
 
 Article can be found at: http://www.nytimes.com/2001/01/15/health/AP-Brain-Exercises.html 

Nerve growth factor, a protein that helps neurons maintain connection with the brain, has potential to alleviate Alzheimers. 80 mice were used in a study, half of which had a gene that gives rise to nerve growth factor inserted into their hippocampuses. The gene was activated once the mice acheived adulthood. The mice were divided into three groups, one of which was was kept in their cages, the second were put in the same maze, the third which was put into a different maze every day for the two week study. The mice which had been fortified with nerve growth factor learned the new mazed faster than the control group, and the challange of learning a new maze aided in neuron growth. 

The researchers were trying to fortify the critical pathway for learning that leads from the basal forebrain to the hippocampus. Research with Nerve growth hormone has alrady been begun with human subjects. Based on the success and lack of adverse reaction in the mice, the use of gene manipulation to aide with diseases that lead to neuron degeneration, such as Parkinsons disease as well as Alzheimers, may become feasible. 

I find it interesting that nerver growth factor on its own was not enough to bring about much neuron growth, but an environment where learning was possible was necessary too. 


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



Nerve Growth Factor Treatment May Offer Hope For Diabetics

ST. PAUL, MN -- Sept. 21, 1998 -- Nerve growth factor, a protein that lengthens the survival of nerve cells, may reduce nerve damage in diabetes patients, according to an article in this month’s issue of the journal Neurology. 

This nerve damage, called neuropathy, is common in diabetes patients and often results in loss of sensation, primarily in the feet. Symptoms can include pain, numbness or burning and loss of co-ordination. Patients can lose the ability to feel heat, cold or pain and may not notice injuries to the feet. Infections can develop, and are sometimes serious enough to require amputation. 


"We hope this treatment will address the underlying problem and improve the condition of these nerves," said neurologist and study author Stuart Apfel, MD, of Albert Einstein College of Medicine in Bronx, N.Y. "Right now we can only treat the symptoms, we can't treat the neuropathy itself." 


The study involved 250 people with diabetic neuropathy, age 18 to 60, from 15 sites around the country. Of those, 82 people received a placebo and 168 received the drug, which is called recombinant human nerve growth factor. All received injections three times per week for six months. 


Those patients taking the drug were more responsive to heat, cold and other sensations compared to those receiving a placebo. When asked whether their symptoms had improved during the study, about 75 percent of those receiving the drug responded positively, compared to 49 percent of those on placebo. 


"Many patients said they had dramatic improvements in their levels of pain and discomfort," Apfel said. 


The most common side effect experienced was mild to moderate discomfort at the injection site. Because of this side effect, most people receiving the drug correctly guessed that they were receiving the drug and not the placebo and most of those examining the study participants correctly guessed whether a patient was receiving the drug or placebo. 


"This can be a criticism of the study, but we don't feel the results were compromised," Apfel said. "The results that showed the beneficial effect of the drug were objective measures. The more subjective measures did not show a beneficial effect." 


Researchers are now studying more than 1,000 patients for at least a year to see whether the drug again shows a benefit for patients. This time the placebo injection also gives patients mild discomfort at the injection site so patients and examiners won't know whether they're receiving placebo or the drug. 


Researchers aren't clear how nerve growth factor may restore function to these nerves. Diabetes may affect the body's ability to produce nerve growth factor, which occurs naturally. It may also affect the body's ability to transport the naturally occurring nerve growth factor from the skin tissue back to the nerve cells. 


"Injecting the nerve growth factor allows it to go directly to the nerve cells that need it," Apfel said. 


Half of all patients who have had diabetes for 20 years or more develop this type of nerve damage.



BOSTON LIFE SCIENCES' NERVE GROWTH FACTOR 
DEMONSTRATES POTENTIAL AS A NEW TREATMENT FOR GLAUCOMA

Boston, MA-December 11, 1998. Boston Life Sciences, Inc. (NASDAQ: BLSI) announced that results achieved in animal model experiments involving the Company's Central Nervous System (CNS) growth factor Axogenesis Factor 1 (AF1) demonstrated re-growth of severed axons within the optic nerve in mice. Since degenerative injury to the optic nerve produces the destruction of vision suffered in glaucoma, these preliminary successes suggest that AF1 could potentially be used as a treatment for this major cause of blindness in the developed countries, the Company said.

"To our knowledge, this is the first time that optic nerve regeneration has reportedly been achieved by intraocular injection of a single nerve growth factor. In these experiments, the optic nerves in mice were partially severed and the mice were then treated with one injection of AF1 administered into the posterior chamber of the eye. Treated animals showed histologic evidence of substantial optic nerve regeneration across the lesion, whereas control animals showed insignificant or no evidence of regeneration in their optic nerves.

Though much work needs to be done to confirm and elaborate these preliminary results as well as optimize drug delivery and dosing, these exciting data suggest that AF1 has the potential to be a totally novel approach to the treatment of glaucoma," stated Dr. Marc E. Lanser, MD, Chief Scientific Officer of BLSI. "This important in vivo activity of AF1 is consistent with both our prior in vitro data demonstrating the potent axon regenerative activity of AF1, and significantly complements our recently reported positive results in experimental spinal cord axonal regeneration.

The Company's CEO, David Hillson commented, "Coming on top of our previously reported positive results for Troponin as an anti-angiogenic approach to the treatment of macular degeneration and diabetic retinopathy, we will want to include our CNS program for consideration by potential ophthalmic partners. Given our assessment of the importance of both of these recent experimental successes, we now believe that the value of our CNS program could potentially achieve equal status with our more well-known technologies."

BLSI is developing novel treatments for cancer, autoimmune disease, and central nervous system disorders. Products awaiting FDA review, in clinical trials or in preclinical development by BLSI include THERAFECTIN for the treatment of Rheumatoid Arthritis; AF1 and other nerve growth factors for the potential treatment of stroke and spinal cord injury; Altropane, a radioimaging agent for the diagnosis of Parkinson's Disease; Troponin as an anti-angiogenic treatment for cancer, and transcription factors that may control the expression of molecules associated with autoimmune disease and allergies.

The foregoing contains forward-looking statements with regard to product development timelines, the implication of experimental results and eventual clinical indications, any of which may not result in approved products due to the uncertainties inherent in the research and development process.