Hokkaido University　Graduate School of Agriculture

Isolational and Structure Elucidation of Bioactive Compounds from Natural Materials (Foods and Medicinal Plants)

Nature produces various interesting bioactive compounds that will work to improve our health. We are searching for those effective compounds from natural materials including foods and medicinal plants.

Search for natural materials and their bioactive compounds for prevention of "Disorders related to metabolic syndrome" (Obesity, Diabetes mellitus)

Metabolic syndrome is a condition that is thought to be the related to several lifestyle related diseases. We are expecially interested in studies related to diabetes mellitus and obesity, and are currently working on search for bioactive compounds against these diseases.

Alpha-glucosydase and alpha-amylase inhibitors

Alpha-glucosidases (amylase, maltase, sucrase, etc...) are an enzymes responsible for the digenstion of polysaccharide like starch. Since the resulting product, i.e. glucose, is concerned in the rapid elevation of blood glucose level, inhibition of these enzymes are helpful to control the blood glucose level of diabetes patients and is also to prevent development of diabetes.

Pancreatic lipase inhibitors

Lipase is a enzyme that hydrolyzes triglyceride to free fatty acids and monoacylglycerol. When we consume fat, which is usually triglyceride, large part of the fat is first hydrolyzed by lipase and the resulting fatty acids and monoacylglycerols are then absorbed from the intestine. If, the fat is kept away from this enzyme, triglycerides remains in their structure and large part of them escape from absorption. Therefore, inhibition of this enzyme will decrease the risk of overtaking energy source when one overeat fats.

Glucose uptake enhancers (insulin mimetics)

When our body detects elevation of blood glucose level, the peptide hormone INSULIN is secreted from beta-cell of pancreas. Insulin stimulates mainly muscle and adipose cell and enhances uptake of glucose from the blood vessel to inside the cell, thus decreasing the blood glucose level. In nature, there are some compounds that act like insulin. However not many of the bioactive compounds are reported.

PPAR agonists

When we develope diabetic condition, in some cases our body decreases the sensitivity to insulin, the blood glucose lowering hormone. In this case, the PPAR agonist which retreives the sensitivity to insulin is a way to treat the condition.

Search for natural materials and their bioactive compounds to prevent "Androgenetic alopecia; AGA"

Testosterone reductase inhibotor

AGA is the alopecia that is caused by accumulation of male hormone. Dihydrotestosterone is one of the male hormone known to have relationship with AGA. Since dihydrotestosterone is produced from testosterone by the action of testosterone 5alpha-reductase, the inhibitor of this enzyme is effective for prevention of this condition.

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Design and synthesis of bioactive compounds and mechanistic analysis of bioactive molecules

"Design and synthesis of alpha-amylase inhibitors"

We are searching for alpha-amylase inhibitors from natural materials as listed above. However, we had difficulty in finding this kind of bioactive molecules that is useful from the nature. Thus, we are also trying to develop the novel and efficient alpha-amylase inhibitor by ourself. Refering to the hydrolysis mechanism and sterical structure of alpha-amylase, novel alpha-amylase inhibitors are designed and is undergoing synthesis employing organic chemistry method.

Mechanistic study of 2-aminoresorcinol, a quite simple alpha-glucosidase inhibitor

2-aminoresorcinol is a quite unique and efficient intestinal glucosidase inhibitor. The most interesting point of this compound is that it shows uncompetitive inhibition against both intestinal maltase and sucrase. Uncompetitive inhibitors are known to bind to the enzyme-substrate complex. Thus, 2-aminoresorcinol should be binding to the enzyme at the site different from substrate binding site. We are employing chemical biology method to investigate the binding site of 2-aminoresorcinol and how it inhibits the enzymes.

Mechanistic study of glucose uptake enhancer (insulin mimetics)

As written above, we are searching for insulin mimetics from the natural products. During that research we have already identified few active compounds. However, although we are calling them "Insulin mimetics", we do not known if they really work as the same as insulin. By employing chemical and biological methods, we are working on this point.

Structural analysis of anti-oxidant activity of polyphenols

Polyphenols possess anti-oxidant activity. This is a quite well known benefits of the polyphenol.
However we do not know much about how these compounds exactly show this effecient activity. We are investing the antioxidant activity from the structural insight by using MS and NMR and other analytical methods to exactly understand this activity.

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