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Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β. We developed mnemoPQQ

Background Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. Objective This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to Methods 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). Results A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. Conclusions Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

Prevalence of osteoarthritis (OA) is increasing alarmingly worldwide. Slowing down the progression of OA and diverse locomotive organ disorders is gaining interest in improving the quality of life (QOL) and extending healthy life-span. In a pilot study, intake of a small amount of undenatured type II collagen exhibited suppression of damage to the articular cartilage via oral immune tolerance. It also demonstrated improvement of knee and joint flexibility and mobility with continued intake of undenatured type II collagen (NEXT-II®) derived from chicken sternum cartilage. This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of 12 weeks of regular intake of NEXT-IISixty-four participants were randomized to receive either NEXT-IIFifty-eight participants (placebo = 28; NEXT-IIResults demonstrate that undenatured type II collagen is safe and efficacious in improving knee flexibility and mobility, reducing knee and lower back pain, and enhancing motor function.

Introduction: Undenatured type II collagen, derived from chicken sternum cartilage, is a novel functional ingredient, which has been demonstrated to improve joint health, flexibility and mobility, and enhancing motor functions. Undenatured type II collagen has been commercially available as functional dietary supplement worldwide for many years. Research studies demonstrated its broad-spectrum safety and clinical efficacy. Undenatured type II collagen requires very small amount to exhibit clinical efficacy and hence can be easily consumed over a long period of time as compared to the other joint care functional ingredients such as glucosamine and chondroitin. Since undenatured type II collagen is effective in relatively small amount, its accurate measurement in various dosage forms such as tablets and capsules become crucial to provide consumers optimal cost and joint-health benefits. Objective: In the present study, we modified the previously used Enzyme-Linked Immunosorbent Assay (ELISA) method to determine the active constituents precisely and accurately in formulations to affirm broad spectrum safety and clinical efficacy. Methods: Improved precision ELISA methodology was utilized to determine the amount of undenatured type II collagen extracted from chicken sternum cartilage. A commercially available Chondrex Collagen Detection Kit was used to determine the number of epitope (antigenic determinant) sites on the three-dimensional tightly-folded structured collagen. Time and temperature were set at ≥16 h or preferably within the range of 16 h to 24 h and at room temperatureResults: The results obtained from this improved ELISA method strongly supported the accuracy and validity, which correlates very well with the results of our earlier clinical studies, revealing the efficacy of undenatured type II collagen concentrations used. Furthermore, the modified ELISA method, designed by our team, revealed consistent and reproducible results on the basis of counting the epitope sites in undenatured type II collagen (NEXT-II®) of commercial batchesConclusion: Using this precisely modified ELISA method gave 8% of undenatured type II collagen in NEXT-II®, resulting in 3.2 mg in 40.0 mg of NEXT-II®. It also confirmed that administration of 3.2 mg of undenatured type II collagen a day, both in open-label and randomized clinical trials, was safe and efficacious for joint pain, flexibility and mobility, and motor function. Keywords: Undenatured type II collagen, NEXT-II®, ELISA method, Pepsin

Background: In advancing age population worldwide, joint discomfort and poor locomotive functions are symptoms, which are often detected. Aggravation of such symptoms potentially develops into osteoarthritis (OA) as characterized by the loss of articular cartilage in the joints of the hand, spine, knee, foot, and hip. For joint health complications, selected functional foods are frequently supplemented orally to alleviate such symptoms. In Japan, Foods with Function Claims (FFC) regulatory system is now positioned within the framework of “so-called health foods” allowing to make functional claims such as brain health and weight control claims. Moreover, a wide variety of knee joint care FFC products are presently available in the marketplace and have attracted much attention of the elderly people, expecting improvements in joint locomotive functions such as walking, sitting, standing, and climbing the stairs for the quality of life (QOL). Supplementation of undenatured type II collagen powder (NEXT-II®) in hard capsules has been clinically proven to improve such joint functions fulfilling part of the FFC rigorous guidelines, while ensuring adequate safety as foods is a crucial prerequisite for filing FFC product dossier.Methods: Twenty-two healthy male and female volunteers (age = 20-74 years) participated in this pilot open-label overdose clinical trial over a period of 4 consecutive weeks. All subjects were also monitored and assessed additional 2 weeks after the completion of the NEXT-II® supplementation period as washout or supplement-free period. Subjects took a 10-fold (10-X) dose of NEXT-II® (400 mg NEXT-II/day containing 32 mg of undenatured type II collagen/day). Daily recommended dose of NEXT-II® is 40 mg/day (containing 3.2 mg of undenatured type II collagen/day) after breakfast. Physical health examination, hematological analysis, blood ,biochemistry examination, and urinalysis were performed. All subjects completed the supplementation of NEXT-II® for 4 weeks and had additional 2 weeks of washout or supplement-free period. All subjects recorded daily diaries. Results: Results demonstrated no significant differences at 0 week (baseline), 2 weeks, and 4 weeks of NEXT-II®supplementation. Furthermore, no significant differences were observed even after 2 weeks of the washout period. No adverse events were observed.Conclusions: Supplementation of 10-fold dose of NEXT-II® to the volunteers was well-tolerated and exhibited the broad-spectrum safety without observing any adverse effects in healthy Japanese subjects.Keywords: Undenatured type II collagen, NEXT-II®, Safety, Overdose supplementation, Clinical study, Foods with Function Claims (FFC)

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.

Supplementation of beta-hydroxy-beta-methylbutyric acid (HMB), a metabolite of the branched chain amino acid leucine, has been examined in light of improving muscle loss. This chapter describes a systematic review, in which HMB is shown to improve muscle mass and strength during exercise. MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov databases were used to search from the earliest possible year to July 2017. Participants were healthy subjects of all ages using HMB without any cosupplement. Two review authors working independently reviewed all randomized double-blinded trials on chronic (≥4 weeks) dosing. Nine studies met the inclusion criteria resulting in 360 subjects. Overall quality of all included trials was low risk or unclear of bias, and quality of reported information was high. From the review of the results, this systematic review revealed that HMB has the potential to increase muscle mass and strength during exercise.

A new function claim system within the framework of health foods, Foods With Function Claims (FFC), was added in Apr. 2015 into preexisting health claim systems such as Foods With Specified Health Uses (FOSHU) and Foods With Nutrient Function Claims, while so-called health foods continued to be a large part of health foods. A striking difference between FFC and FOSHU in the categorization is that FFC adopts a registration or notification system. Consequently, the safety and efficacy (function claims) of any FFC product should have scientifically evidence for which applicants (sellers) take responsibilities in documenting, whereas FOSHU is performed within a government approval system. The Consumer Affair Agency's major aims of implementing FFC are to provide consumers with an opportunity to select foods with function/health claims and vitalize the health foods market, allowing small to medium-size enterprises to capitalize on FFC.

Background: Oral administration of a novel water-soluble undenatured type II collagen (NEXT-II®) has been demonstrated to ameliorate the signs and symptoms of rheumatoid arthritis (RA) in animal models. In the present investigation, we conducted a pilot study to examine the efficacy and safety of NEXT-II® in borderline subjects defined as healthy and non-diseased state, but with potential risks in knee joint health. Method: We employed Western Ontario McMaster Index (WOMAC) score and Visual Analog Scale (VAS) scores to assess the extent of improvement in the knee joints in these volunteers following supplementation of 40 mg NEXT-II® (10 mg as undenatured type II collagen) over a period of 12 weeks. Result: The results demonstrated that NEXT-II® treatment significantly reduced WOMAC and VAS scores compared to subjects at baseline. Specifically, in the evaluation using VAS, the borderline subjects at resting, walking, and going up and down the stairs revealed significant improvement when compared to the baseline. Conclusion: The results of the studies demonstrated that NEXT-II® might be an ingredient which is safe and effective in the application of dietary supplement in ameliorating joint pain and symptoms of the borderline subjects without any adverse events.

Background: Nutraceuticals and functional foods are increasingly being used to help manage hypertension. Treatment with either pumpkin or onion can significantly lower systolic and diastolic blood pressure in animal studies. Traditionally, pumpkin has been used to support healthy blood pressure, glucose tolerance and lipid levels. Onion contains high levels of flavonoids, including quercetin, which decreases blood pressure and promotes restoration of healthy endothelial function. However, human trials on these food sources are limited, and the combined effects of pumpkin and onion have not been examined yet.Objective: We performed an open-label clinical study to evaluate the effects of a proprietary onion-pumpkin extract (OPtain120) on systolic and diastolic blood pressure.Methods: Healthy adults with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the elevated range of 140-159 and 80-90 mmHg, respectively, were enrolled in this study. Subjects consumed one capsule of onion-pumpkin extract twice daily for 12 weeks. Daily Home Blood Pressure Measurement (HBPM) was taken upon waking and before bed. Office Blood Pressure Measurement (OBPM) was taken in-clinic at Week 0, 6, and 12.Results: 52 subjects were screened and 12 were enrolled in the study, with a total of 10 subjects completing the study. Systolic HBPM taken before bed demonstrated a statistically significant reduction from baseline (147.23 mmHg) to Week 12 (138.14 mmHg), representing a reduction of 9.09 mmHg (6.17%, p=0.021). Diastolic HBPM taken before bed demonstrated a decrease of 4.06 mmHg (4.46%, p=0.085), a significant reduction from baseline (91.07 mmHg) at Week 12 (87.02 mmHg). Non-statistically significant reductions were seen in the early morning Systolic (3.14%) and Diastolic (2.57%) HBPM and in the Systolic (1.36%) OBPM.Conclusion: OPtain120 was safely consumed over a 12-week period. OPtain120 appears to be effective in lowering Systolic Blood Pressure at bedtime in healthy individuals with slightly elevated blood pressure. This study suggests that onion-pumpkin extract may aid individuals who manage their cardiovascular risk factors with diet and lifestyle.Key Words: pumpkin, onion, extract, blood pressure

Background: Fatigue is attributable to physical and psychological stress. Fatigue is also a common symptom which occurs in both sick and healthy individuals. Although its mechanism of cause is complex, fatigue from stress is known to affect the existing equilibrium of the immune system. However, nutrition, such as beta-1,3/1,6 glucan, has been reported to play an important role in regulating stress and fatigue states, via modulating a weakened immune system. In this study, a popular and healthy beverage in Okinawa, Japan, containing a soluble baker’s yeast in black koji vinegar (Moromisu), was provided to healthy subjects with a non-strenuous daily lifestyle.Results: By performing statistical analysis on the results of the Profile of Mood States (POMS) survey, we observed that overall study results (n=14) demonstrated significant differences in fatigue and confusion in the POMS factors.Conclusions: In this study we confirmed that beta-1,3/1,6 glucan improved some of the factors related to stress and fatigue, as indicated by evaluation of POMS survey results.Key Words: Beta-1,3/1,6-glucan, vinegar, POMS, stress

Japanese, on average, live longer according to the demographic data of Ministry of Internal Affairs and Communications, as shown in the population pyramid changes over 100 years. For example, aged adults frequently visit clinics or hospitals even for slight illness or as regular health examinations because their medical costs are in part reimbursed by the government. The reimbursement system worked well supporting the aged adults, which potentially prevented them from degenerative diseases. Royal jelly (RJ) is a secretion material of the cephalic glands of nurse bees. Its role has attracted academia, because it possesses unique and important biological features and health benefits. RJ is enriched with minerals, vitamins, and many other nutritional as well as functional components. Although many functional ingredients are yet to be isolated and identified for their functions, such ingredients for health benefits were previously reported and used as drug and functional food ingredient.

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-Freund's 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.

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.

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.

The role of green coffee bean (GCB) in human health is of emerging interest to the nutraceutical field, especially given its role in improving metabolic syndrome, including weight management, hypertension, diabetes, and neuroprotection. GCB extract contains a novel antioxidant known as chlorogenic acid (also caffeoylquinic acid), which has been shown to positively affect blood pressure, brain health, diabetes, and weight management. This book provides information on the diverse health benefits of green coffee bean extract, molecular mechanisms and signaling pathways, safety of GCB, dosage, and recommended usage. It focuses on the chemistry, biochemistry, pharmacology, and safety of GCB extract. GCB extract has brought a remarkable revolution in the nutraceutical marketplace. However, some controversies have been demonstrated recently. This book presents the state-of-the-art research studies from eminent scientists around the world on the potential and diversified health benefits of GCB extracts, with particular emphasis placed on the importance to standardize the appropriate extraction technology, quality control and assurance, and broad spectrum safety studies and human clinical studies to substantiate the regulatory claims and position the product in the marketplace.

Overview and Pathophysiology An Overview on Rheumatologic Disorders, S. Kumar and R. Gupta Pathogenesis of Osteoarthritis, A.P. Anandarajah Biomarkers in Osteoarthritis, M. Ishijima, H. Kurosawa, H. Kaneko, and K. Kaneko Rheumatoid Arthritis: Disease Pathophysiology, A. Saxena, S.K. Raychaudhuri, and S.P. Raychaudhuri Osteoclasts and Interleukin-17-Producing Helper T Cells in Rheumatoid Arthritis, K. Okamoto and H. Takayanagi WNT/ss-Catenin Signaling Modulating Osteoarthritis, M. Corr Psoriatic Arthritis: Epidemiology, Risk Factors, and Quality of Life, A.R. Setty Consequences Arthritis, Obesity, Increased Cardiovascular Risk, and Disability, S. Chatterjee Antiarthritic Drugs An Overview: Use of Traditional Antiarthritic Drugs and Update on Drug Development, G. Schmajuk and M.G. Lyon Nonsteroidal Anti-Infl ammatory Drugs, A. Lal and S. Sharma Biologics: Target-Specifi c Treatment of Systemic and Cutaneous Autoimmune Diseases, S.P. Raychaudhuri and S.K. Raychaudhuri Topical Applications for Pain and Arthritic Diseases, N. Tanida, K. Maekawa, and M. Nakanishi Hyaluronic Acid and Arthritis: A Review, M. Abate Hyaluronan for the Treatment of Osteoarthritis and Rheumatoid Arthritis, T. Nakano and Y. Takahashi Natural Therapeutic Interventions Immunomodulatory Activities of Japanese Traditional Medicines in Rheumatoid Arthritis, T. Kogure An Overview on Natural Therapeutic Interventions, S. Naguwa Potential Health Benefi ts from Nutrition and Dietary Supplements in the Prevention of Osteoarthritis and Rheumatoid Arthritis, C.C. Rosenbaum Antiarthritic Potential of Glucosamine and Chondroitin: An Overview, M.W. Orth and P.S. Chan An Overview on N-Acetylglucosamine and Arthritis, D. Kubomura, U. Naoaki, and Y. Matahira Hexosamine Flux and the Efficacy and Safety of Glucosamine in the Treatment of Osteoarthritis, A. Afshan A.W. Salminen, and J.E. Leakey Safety and Efficacy of a Unique Undenatured Type II Collagen in the Treatment of Arthritis, S.P. Raychaudhuri, R.C. Gupta, H. Moriyama, M. Bagchi, F.C. Lau, and D. Bagchi Targeting Inflammatory Pathways by Nutraceuticals for Prevention and Treatment of Arthritis, B. Sung, G. Sethi, K.S. Ahn, M.K. Pandey, A.B. Kunnumakkara, and B.B. Aggarwal Boswellia serrata for Arthritis Relief: A Journey from Frankincense to Aflapin and 5-Loxin, A.V. Krishnaraju, K. Sengupta, S.P. Raychaudhuri, and G. Trimurtulu Utilization of Marine Products in the Treatment and Prevention of Osteoarthritis, T. Tamai, A. Honmura, H. Yoshioka, T. Konishi, S. Kuninaga, H. Oda, A. Sakamoto, and T. Okada Benefits of Fish Oil for Rheumatoid Arthritis: A Review, C. Dawczynski and G. Jahreis Potential Health Benefits of n-3 and -6 Fatty Acids in Selected Plant Seed Oils in Rheumatoid Arthritis, H. Takeuchi, H. Moriyama, D. Bagchi, and S.P. Raychaudhuri Antiarthritic Potential of Bromelain from Ananas comosus and Its Combination, D. Ghosh Anti-Inflammatory Properties of Zingiber officinale var. Rubra (Red Ginger Extract), H. Shimoda Benefits of Radix Tripterygium wilfordii for Rheumatoid Arthritis, X. He, S. Xu, M. Jiang, N. Lin, and A. Lu Dehydroepiandrosterone (DHEA): A Review of Its Preclinical Use in the Management of Osteoarthritis, K. Huang, H.l. Cai, C. Zhang, X.-w. Zhang, L.d. Wu, L.f. Shen, and Q.f. Guo Antiarthritic Potential of Green-Lipped Mussel and Other Marine-Based Nutraceuticals, W. Pearson and M.I. Lindinger Antioxidant, Anti-Inflammatory, and Anticatabolic Potential of Rosmarinic Acid and High-Rosmarinic Acid Mint (Mentha Spicata) in Osteoarthritis, W. Pearson and M.I. Lindinger Potential Health Benefits of Orally Administered Hyaluronan in Alleviating Knee Joint Pain, T. Kanemitsu and A. Asari PycnogenolA Nutraceutical for Osteoarthritis, O.P. Gulati Orthopedic Approach Total Knee Arthroplasty for Osteoarthritis, S. Matsuda, H. Miura, and Y. Iwamoto Nonpharmacologic Interventions Physical Exercise for Osteoarthritis of the Knee: Main Modality of Treatment and Possible Use for Prevention, H. Kurosawa Acupuncture for the Treatment of Arthritis, H.J. Park and H. Lee Rehabilitative Strategies for Arthritis: Physical, Agents, Exercise, and Prosthesis Therapies, N. Kawate, M. Yoda, N. Yoshioka, and M. Mizuma Rehabilitation for Arthritis: Daily Life Guidelines, F. Kasai and M. Mizuma Commentary Arthritis, Aging Society, Exercise, Nutrition, and Other Precautionary Measures, S.P. Raychaudhuri, H. Moriyama, and D. Bagchi Index

Background: Mangoes are a popular fruit enjoyed worldwide. The mango is known for its pleasing aroma in addition to its refreshing and soothing taste. Researchers around the globe have demonstrated the diverse beneficial effects of Mangifera indica Linn in human health and disease prevention. Additionally, we should acknowledge how Ayurvedic medicine uses different parts of the mango tree. This branch of medicine has used the leaves, twigs, bark, seeds, flowers, raw and ripe fruits of mango to treat diverse degenerative diseases for thousands of years. Ethnobotany: The mango ( Mangifera indica ) originally came from India about 4,000 years ago. Since then, the mango has slowly spread across the world. The mango belongs to the family “Anacardiaceae” under the genus “ Mangifera ” and species “ indica ”. The mango is also referred to as “Asia’s King of Fruits” or a Royal fruit. The color of the mango fruit varies from green, yellowish green, yellow, yellowish red, orange red and red. The smell and taste of the mango fruit varies based on its state of maturity in addition to place of origin and climate. Different parts of a mango tree and mango fruit are rich in vitamins and antioxidants including vitamins B, C, E and beta-carotene, alkaloids, flavonoids, and polyphenolic compounds which include mangiferin, anthocyanins and anthocyanidins, micronutrients and essential minerals, structurally diverse carbohydrates, dietary fibers, fat, and protein. Health Benefits: Previous and current research demonstrate that the mango fruit and leaf extract, which is enriched in mangiferin and contains structurally diverse chemical constituents, are beneficial. The mango fruit and leaf extract have been shown to boost vitality, vigor, and endurance, leading to extensive application in exercise physiology. Furthermore, these constitutes ameliorate diverse degenerative disease related to metabolic syndrome, bacterial infections, gastrointestinal, and immunomodulatory disorders. Conclusions: Mango and mangiferin exhibit diverse health benefits including energy boosting, exercise performance, and human health. Keywords: Mango ( Mangifera indica) ; mangiferin; vitamins and anthocyanins; anti-inflammatory; endurance, energy homeostasis; exercise

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.

A particle-counting aggregometer employing laser-light scattering was used in systematic manners to screen and to detect inhibitor(s) of platelet aggregation from the extract of Malbranchea filamentosa (M. filamentosa) IFM41300. The inhibitor was determined as adenosine on the basis of the 13C- and 1H-NMR spectral data. Although adenosine was previously reported as an inhibitor of platelet aggregation, we isolated the compound from the fungus for the first time. Because the method was able to provide us with information on the developmental formation of platelet aggregates in different sizes with incubation time, we further elaborated the inhibitory behaviors of adenosine, as an example, at varied concentrations in different solvents such as dimethyl sulfoxide (DMSO) and saline. We found that DMSO could facilitate to dissolve less water soluble materials from herbs and fungi by using the present assay method.

Dihydroterrein (1) and terrein (2) were isolated from methanol extracts of the solid culture of Asperillus novofumigatus IFM 55215. Both 1 and 2 inhibited human platelet aggregation induced by collagen at a concentration of 5.0 × 102 μmol/L in vitro and they displayed slight inhibitory effects when platelet aggregation was induced by adenosine diphosphate (ADP). Inhibitory activity of dihydroterrein diacetate (3) and terrein diacetate (4) on platelet aggregation was also examined. Compound 4 was found to possess the highest inhibitory effect on both collagen- and ADP-induced platelet aggregation among 1 - 4.

Antiinflammatory activities of heat-treated Cassia alata leaf extract and kaempferol 3-O-gentiobioside(K3G) isolated from C. alata as an abundant flavonoid glycoside were studied by comparing their activities with the activities of sun-dried C. alata leaf extract. We observed strong inhibitory effects on Concanavalin A-induced histamine release from rat peritoneal exudate cells both in the extracts of heat-treated and sun-dried C. alata leaves. Furthermore, the heat-treated leaf extract exhibited stronger inhibitory effects than the effects of the sun-dried leaf extract at low concentrations in the studies of Concanavalin A-induced histamine release, 5-lipoxygenase inhibition, and also inhibition of cyclooxygenases (COX-1 and COX-2), whereas K3G showed weak inhibitory effects on Concanavalin A-induced histamine release, 5-lipoxygenase, and COX-1. No anti-hyaluronidase effect was detected in any of the materials tested.

Kaempferol-3-O-gentiobioside, the major flavonoid glycoside in Indonesian Cassia alata was quantified in various parts of the plant. The mature leaf was found to contain the highest content of this metabolite. A decrease of the flavonoid content in the juvenile leaf during the period of October through December was also observed. The contents ranged from 2.0 to 5.0% and 1.0 to 4.0% in mature and juvenile leaves, respectively. The other parts studied were flower (sepal and petal), rachis, stem and seed. Kaempferol-3-O-gentiobioside was not detected in the seed.

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.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.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.

Placenta is an important organ that connects the developing fetus to allow nutrient uptake, antibody provisions and gas exchange via the blood supply of the mother. We developed a novel, standardized, stable, water-soluble, peptide-enriched hydrolyzed, Horus fermented placenta powder (HFPEP) from healthy, pathogen-free, swine placenta. Earlier studies demonstrated that HFPEP significantly improves physical fatigue, hepatic functions and repair of muscle fibers. We examined the broad safety of HFPEP in various toxicology models in Good Laboratory Practices-approved laboratories. The acute oral toxicity study was conducted in female Sprague-Dawley rats, and the acute oral LD50 was found to be greater than 5000 mg/kg body weight. Ames' bacterial reverse mutation assay was conducted to determine the ability of HFPEP to induce reverse mutation at selected histidine loci in five tester strains of Salmonella typhimurium viz. TA1535, TA1537, TA98, TA100 and TA102 in the presence and absence of a metabolic activation system (S9) at the doses of 50, 15, 4.5, 1.35 and 0.41 mg/ml. No mutagenic potential was observed. Mutagenic potential was also evaluated using in vivo micronucleus test, and no mutagenic potential of HFPEP was observed. Repeated dose 28-d oral toxicity study was performed in male and female rats with 14-d recovery period at the dose levels of 250, 500 or 1000 mg/kg. No abnormal clinical signs or toxicity were detected. No observed adverse effect level of HFPEP was found to be greater than 1000 mg/kg body weight. These studies affirm that HFPEP has broad spectrum safety for human consumption.

Heat-treated leaves of Cassia alata were studied for any change in chemical constituents using sun dried leaves as the reference standard. A high concentration of a constituent was observed in the heat-treated leaves. Spectroscopic studies revealed the structure of the constituent as kaempferol 3-gentiobioside, which has not yet been detected in the Cassia species. In a stability study disappearance of kaempferol 3-gentiobioside was noted in the sun dried leaves while there was little or no change in the kaempferol 3-gentiobioside concentration in the heat-treated leaves when incubated in an aqueous solution, suggesting a possible presence of enzymatic activities in the sun dried leaves. Therefore, heat-treatment may be a good method to stabilize kaempferol 3-gentiobioside in Cassia alata leaves.

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.

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.

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.