Hiroyoshi Moriyama

Bio-nanotechnology : a revolution in food, biomedical and health sciences

Bio-nanotechnology is the key functional technology of the 21st century. It is a fusion of biology and nanotechnology based on the principles and chemical pathways of living organisms, and refers to the functional applications of biomolecules in nanotechnology. It encompasses the study, creation, and illumination of the connections between structural molecular biology, nutrition and nanotechnology, since the development of techniques of nanotechnology might be guided by studying the structure and function of the natural nano-molecules found in living cells. Biology offers a window into the most sophisticated collection of functional nanostructures that exists.

Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.

Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freunds complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-β1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells.

Vasorelaxant effects of forsythide isolated from the leaves of Forsythia viridissima on NE-induced aortal contraction

Forsythide (F1) isolated from the leaves of Forsythia viridissima (Oleaceae) showed vasorelaxant effects on norepinephrine (NE)-induced contraction of rat aorta with or without endothelium. This compound did not affect contraction induced by high concentration potassium (60 mM K(+)) and phorbol 12,13-diacetate, but inhibited NE-induced contraction in the presence of nicardipine. These results demonstrated the inhibitory effects of F1 on NE-induced vasocontraction presumably due to decrease of calcium influx from extracellular area, which was induced by NE.

Safety and toxicological evaluation of a novel, water-soluble undenatured type II collagen

Abstract This study was conducted to determine the broad-spectrum safety of a novel, water-soluble undenatured type II collagen (NEXT-II) derived from chicken sternum cartilage. The presence of epitope in NEXT-II was confirmed by using a commercial kit. The acute oral LD50 of NEXT-II was found to be greater than 5000 mg/kg bw in rats, while the single-dose acute dermal LD50 was greater than 2000 mg/kg bw. The primary dermal irritation index (PDII) of NEXT-II was found to be 1.8 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score (MMTS) of NEXT-II was observed to be 7.3 and classified as minimally irritating to the eye. Long-term safety studies were conducted in dogs over a period of 150 d, and no significant changes were observed in body weight, heart rate, respiration rate and blood chemistry. NEXT-II does not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Furthermore, two experiments were conducted to assess the potential of NEXT-II to induce mutations with and without metabolic activation at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. No biologically relevant increase of mutants was observed. Also, no dose-dependent toxicity was observed. Furthermore, colony sizing showed no clastogenic effects induced by NEXT-II under the experimental conditions. These studies demonstrated the broad spectrum of safety of NEXT-II.

Chapter 17 – Health Foods and Foods with Health Claims in Japan

Publisher Summary The presence of the four distinct seasons with appropriate temperature and humidity in Japan surrounded by sea fostered the Japanese food eating habit and created a distinctive Japanese food culture. The term “health foods” (HF) is commonly used in Japan to describe what may be called “functional foods” (FF) or “dietary or food supplements” in the USA and other countries. This chapter serves to enhance understanding of HF in relation to various regulatory systems and safety concerns in consumers. The “Foods with Specified Health Uses” (FOSHU) concept is described as it evolved from FF which was first developed and published for the health benefits of foods in our country in 1984. In 1991, the Ministry of Health and Welfare (MHW), now known as the Ministry of Health, Labor and Welfare (MHLW), officially presented the FOSHU system as a basis for making the functional claims of foods (FD). It was in reference to the increase in the occurrence of lifestyle-related diseases (LSRD) that include diabetes mellitus, high blood pressure, cerebro- and cardiovascular diseases and cancer. In 2001, a new regulatory system, “Foods with Health Claims” (FHC) was established and consisted of a new concept of “Foods with Nutrient Function Claims” (FNFC) and innovated FOSHU. In 2005, the MHLW additionally changed the existing FOSHU system. Such change includes the new subsystems of FOSHU: standardized FOSHU, qualified FOSHU and disease risk reduction claims. Lastly, issues directed to the safety and quality of raw materials and HF products are also discussed with the focus on two guidelines that require good manufacturing practice (GMP) and self-investigating systems for safety of raw materials.

An Overview of a Novel, Water-Soluble Undenatured Type II Collagen (NEXT-II)

Background: Osteoarthritis, the most common form of arthritis, is a crippling, chronic debilitating bone disease that commonly affects humans, dogs, and horses. Inflammation and inflammatory responses are key factors for causing swelling, redness, pain, and loss of movement in arthritic animals and humans. Methods and Results: We developed a novel, water-soluble, undenatured type II collagen (NEXT-II) for osteoarthritis. NEXT-II demonstrated broad-spectrum safety and nonmutagenicity. NEXT-II exhibited significant efficacy in ameliorating pain and inflammation in collagen-induced arthritis in mice. NEXT-II enhanced the proportion of CD4+CD25+T cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cell such as forkhead box p3, transforming growth factor-β1, and CD25. Furthermore, NEXT-II was assessed in moderately arthritic dogs receiving either placebo or 10 mg NEXT-II over a period of 150 days. NEXT-II exhibited a significant reduction in overall pain, pain after limb manipulation, and pain after physical exertion compared to the control dogs. Physical health and serum chemistry (alanine aminotransferase, blood urea nitrogen, and creatine kinase) were not altered when these arthritic dogs were treated over a period of 150 days. Conclusions: These results demonstrate the broad-spectrum safety and efficacy of NEXT-II in ameliorating the symptoms of arthritis. Key Teaching Points: •A novel, water-soluble, undenatured type II collagen (NEXT-II) was developed for osteoarthritis. •The safety studies including acute oral and dermal toxicity, primary dermal and primary eye irritation, Ames’ bacterial reverse mutation assay, mouse lymphoma assay, and 150-day long-term safety studies were conducted. •NEXT-II exhibited significant efficacy in ameliorating pain and inflammation in collagen-induced arthritis in mice. •NEXT-II exhibited a significant reduction in overall pain in moderately arthritic dogs without changing physical parameters.

Safety of oligonol, a highly bioavailable lychee-derived polyphenolic antioxidant, on liver, kidney and heart function in rats.

Oligonol (OLG), derived from lychee fruit, is a novel compound produced from the oligomerization of polyphenols. In this study, the acute effect of OLG treatment was investigated on heart, liver and kidney in rats. OLG treatment at two different doses (15 or 30 mg/kg body weight) and two different time points (1 day or 7 days of treatment) demonstrated that no toxic effects were observed on heart, liver and renal functions. Moreover, OLG did not induce any DNA damage or oxidative stress as measured by 8-hydroxy-2′-deoxyguanosine levels in plasma. OLG supplementation increased the phosphorylation of myocardial endothelial nitric oxide (NO) level (p-eNOS) in both the treatment groups. Even the low dose OLG treatment (15mg/kg b.w) demonstrated an increase in p-eNOS/eNOS ratio after normalization of p-eNOS values with eNOS on day 1 (1.5-fold) and day 7 (2.2-fold) groups as compared to control. The above results suggest that OLG treatment increases endothelial NO levels and may play a role in NO-mediated vasodilatory effects without adverse side effects on cardiovascular function. This endothelial NO production may underlie the beneficial effect of OLG in cardiovascular health.

Royal Jelly in Medicinal to Functional Energy Drinks

Abstract Royal jelly (RJ), which is secreted by the hydropharyngeal gland of worker bees, has a broad spectrum of beneficial physiological properties. It is primarily used to nourish worker bees as well as queen bees. The antioxidant properties of RJ are attributed to proteins and/or peptides, which are potentially associated with the amelioration of fatigue. Muscle-enhancing performance can also be increased with the supply of oxygen in conjunction with RJ. RJ has also been demonstrated to improve erythropoiesis. These results have been confirmed in clinical trial results. However more clinical evidence is required to confirm its efficacy. Overall, RJ is safe and efficacious in a variety of functional beverages to boost energy and performance.

Salient Features for Designing a Functional Beverage Formulation to Boost Energy

A growing body of evidence indicates that energy drinks, energy shots, and energy drink instant mixes and sachets are becoming increasingly popular worldwide and their consumption and popularity are rapidly increasing. These energy beverages promise to provide consumers an additional energy boost. However, most energy beverages available on the market are loaded with sugar, caffeine, and excess calories. It has been demonstrated that caffeine interacts antagonistically with many foods and drugs, so extensive research studies should be conducted before introducing a high amount of caffeine into the beverage formulations. The right dose of caffeine should be determined meticulously. This review discusses important criteria for designing novel functional beverages to boost energy and critically evaluates them for their health benefits, safety, and stability.

Nutritional Interventions to Reduce Immune Suppression Post Marathon

In elite level athletes it is commonly believed that there is a link between high-intensity exercise and increased incidence of upper respiratory tract infections (URTI). Physiological changes associated with exercise are well documented on various components of the immune system, including: changes in number of circulating immune cells and their responsiveness, changes in cytokines and chemokines, and changes in mucosal IgA levels. This chapter uses the example of long-distance running to review what is known about the link between intense exercise and URTI incidence, and changes in various immune system parameters after intense exercise. Finally, the ability of nutritional interventions to rebalance the immune system parameters affected by strenuous exercise are reviewed with an emphasis on the ability of yeast beta glucan to mitigate the negative impact of exercise on the immune system.