21st Century COE Program Human Nutritional Science on Stress Control
Research Aim
Dr. Takeda's Labo
Dr. Terao's Labo
Dr. Miyamoto's Labo
Dr. Nakaya's Labo
Dr. Rokutan's Labo
Dr. Chuman's Labo
Dr. Kaji's Labo
Dr. Ohmori's Labo
Dr. Sei's Labo
Dr. Terao's Labo
Prof. Junji Terao
Department of Food Science
http: //www.hosp.med.tokushima-u.ac.jp / university / servlet / index?&level=5&reference=0 / 10002 / 5 / 30010 / 20033 / 40728 Dr. Terao's Labo
Our research is concerned with the tertiary function of foods related to disease prevention and enhancing human health.
In particular, we are investigating bioavailability and physiological function of plant pigments involving flavonoids and carotenoids. Their role in oxidative stress control is studied using cellular and animal models, and human volunteers. In our COE program, we are conducting the evaluation of antidepressant-like effect of foodstuffs and their ingredients using forced swimming test (FST). Several plant and animal foodstuffs were found to be positive to FST and we expect they are promising as stress control foods. We also investigated plant polyphenols as biomodulators of cellular oxidative stress which relates to the disorder of cognitive function. Recent published works suggest that some polyphenols actually accumulate as their metabolites in the brain tissue. Therefore, we now focus on the behavior and function of plant polyphenols in the central nervous system and hypothalamus-pituitary-adrenal cortex system.
Much attention has been paid on the prevention and treatment of depression and its related symptom, as depression is estimated to represent a major disease affecting 3-5 % of the world population. Chronic stress is definitively an essential factor for this disease. Our goal is to control daily stress and then to prevent the depression and other chronic stress-related diseases by the strategy of nutritional science.
The research subject of our group is to find foodstuffs and their ingredients acting as stress-control reagents in relation to anti-depressant activity. We introduced forced swimming test (FST) of rodents as a model to specify foodstuffs with antidepressant-like activity, as this model is frequently used for the screening of antidepressant drugs. Here we examined FST for a wide variety of foodstuffs and ingredients from plant and animal origin. Extracts from Ginkgo biloba leaves, beef extracts, extract of Panax Ginseng, and onion powder were found to possess antidepressant-like activity in this behavioral model. We also confirmed that quercetin, a typical polyphenol present in onion and other plant foods, is positive to FST as well as tail suspension test of mice, an alternative test for antidepressant-like activity. We are therefore interested in the effect of quercetin and other polyphenols from plant origin on brain function, as a lot of literatures suggest that the active components of mental herbs including anti-depressant one such as St John’s wort include quercetin and its structure-related polyphenols.
We recently succeeded in synthesizing an anti-quercetin metabolite antibody and applied it to the immunohistochemical analysis of quercetin metabolites which accumulate in the human vascular tissues. We discovered that the quercetin metabolites accumulate in atherosclerotic aorta, but not normal aorta. This methodology is undoubtedly useful to know the accumulation of dietary quercetin and other polypohenols in brain tissue and the target molecule in central nervous system.
atherosclerotic aorta & normal aorta
The transport system from blood stream to brain crossing the blood brain barrier is an unresolved subject. We started the research on the transport system of polyphenols using the cell culture model for blood brain barrier.
On the other hand, polyphenols are well known to act as powerful antioxidants. We already clarified that quercetin metabolites are able to protect PC12 cells, a model of nerve cell, from lipid hydroperoxide-induced cellular oxidative stress. In addition, polyphenols may also affect the nerve function by the activity different from antioxidants, that is, so-called “beyond the antioxidants”. Thus, we are focusing on the two points in a mechanism study for polyphenols in stress control research. One is that the modulation of neurotransmitters in brain tissues. The other one is the control of stress hormone in hypothalamus-pituitary-adrenal cortex (HPA) system. Recently, we are trying to elucidate the effect of dietary polyphenols on the generation of cortisol and its related stress hormones under the load of stress.
Finally, we are expecting to find foodstuffs and their gradients successfully used to overcome mental stress without side effect in near future.
  1. Sakakibara H, Ishida K, Izawa Y, Minami Y, Saito S, Kawai Y, Butterweck V, Tamaki T, Nakaya Y, Terao J. Effects of forced swimming stress on rat brain function. J. Med. Invest. 52 Suppl:300-301 (2005)
  2. Shirai M, Kawai Y, Yamanishi R, Terao J.Approach to novel functional foods for stress control 5. Antioxidant activity profiles of antidepressant herbs and their active components.J. Med. Invest. 52 Suppl:249-251 (2005)
  3. Shirai M., Kawai Y, Yamanishi R, Kinoshita T, Chuman H, Terao J Effect of conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroeproxide-dependent formation of reactive oxygen species in differentiated PC-12 cells. Free Radical. Res. 40,1047-1053 (2006)
  4. Sakakibara H, Ishida K, Grundman O, Nakajima-J, Seo S, Butterweck V, Minami Y, Saito S, Kawai Y, Nakaya and Terao J. Antidepressant effect of extracts from Ginkgo Biloba leaves in Behavioral models Biol. Pharm. Bull.29, 1767-1770 (2006)
  5. Kinoshita t, Lepp Z, Kawai Y, Terao J, Chuman H. An integrated database of flavonoids. Biofactors 26, 179-188 (2006)
  6. Kawai Y, Miyoshi M, Moon J-H, Terao J. Detection of cholesteryl ester hydroperoxide isomers using gas chromatography-mass spectrometry blotting Anal. Biochem. (2007) 360, 130-137
  7. Kawai Y, Kiyokawa H, Kimura Y, Kato y, Tshuchiya K, Terao J. Hypochlorous acid-derived modification of phospholipids:characterization of aminophospholipids as regulatory molecules for lipid peroxidation Biochemistry 45:14201-14211 (2006)
  8. Kawai Y, Takeda S, Terao J. Lipidomic analysis for lipid peroxidation-derived aldehydes using gas chromatography-mass spectrometry Chem. Res Toxicol (2007)20, 99-107.
  9. Minami Y., Yokoi S, Setoyama M., BandoN., Takeda S., Kawai Y ,Terao J. combination of TLC blotting and gas chromatography-mass spectrometryfor analysis of peroxidized cholesterol Lipids (2007) in Press.
  10. Sakakibara H., Yoshino S., Kawai Y., Terao J., Antidepressant-like effect of onion (allium capa L) in a rat behavioral model of depression Biosci. Biotecnol. Biochem (2007) in press.

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