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1.
Nutrients ; 16(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38931190

ABSTRACT

In the present study, we conducted a placebo-controlled, double-blind, parallel-group comparison trial in which an extract of Cordyceps militaris (CM) mycelium was administered to long-distance runners for 16 weeks during the pre-season training period and blood test markers for anemia were investigated. The results indicated that the change rates of serum ferritin levels were moderately increased in the CM group (n = 11) but decreased in the placebo group (n = 11) during the study period, and the levels were significantly increased in the CM group compared with those in the placebo group at 4 weeks and 8 weeks after the test food intake (p < 0.05). Moreover, the change rates of hemoglobin and hematocrit were significantly increased in the CM group compared with those in the placebo group at 8 weeks after the test food intake (p < 0.05). These observations suggest that the intake of test food containing Cordyceps militaris mycelium extract is expected to effectively maintain the hemoglobin and hematocrit levels in long-distance runners, possibly via the suppression of the decrease in iron storage, which is reflected by serum ferritin, during pre-season training. Furthermore, the levels of creatine kinase were increased above the normal range in both the placebo and CM groups at registration. Interestingly, the creatine kinase levels were significantly decreased in the CM group compared with those in the placebo group at 16 weeks after the test food intake (p < 0.05). These results suggest that Cordyceps militaris mycelium extract exhibits a protective action on the muscle damage observed in long-distance runners and may suppress muscle injury. Together, these observations suggest that Cordyceps militaris mycelium extract exhibits an improving effect on the markers for not only anemia, but also muscle injury in long-distance runners during pre-season training.


Subject(s)
Biomarkers , Cordyceps , Hemoglobins , Mycelium , Running , Humans , Cordyceps/chemistry , Double-Blind Method , Male , Biomarkers/blood , Adult , Hemoglobins/analysis , Hemoglobins/metabolism , Hematocrit , Ferritins/blood , Anemia/blood , Anemia/drug therapy , Creatine Kinase/blood , Athletes
2.
Int J Mol Sci ; 25(4)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38396804

ABSTRACT

Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.


Subject(s)
Cholecalciferol , Tumor Necrosis Factor-alpha , Humans , Cholecalciferol/pharmacology , Aging , Flavonoids , Inflammation/prevention & control , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Vitamin D/pharmacology
3.
Article in English | MEDLINE | ID: mdl-38343059

ABSTRACT

BACKGROUND: The Mediterranean diet, listed as the intangible cultural heritage of humanity by UNESCO, is known as healthy and consumed worldwide. The Japanese diet is also listed and considered healthy. This narrative review compares the Mediterranean diet with its Japanese counterpart. DISCUSSION: Research has reported that people in Mediterranean regions, such as Italy and Greece, have one-third of the mortality ratio from cardiovascular diseases compared to people in the United States and Northern Europe because of the difference in eating habits. Therefore, Mediterranean diets are considered as healthy. A typical Western diet containing high amounts of fat, sugar, and calories is responsible for several diseases like metabolic syndrome and obesity, which are induced by chronic inflammation. In contrast, Mediterranean and Japanese diets contain them only less. The similarity between Mediterranean and Japanese diets is the substantial intake of vegetables, beans, and fish. On the other hand, the Mediterranean diet consumes large amounts of olive oil, especially polyphenol-rich extra virgin olive oil and dairy products, but meat consumption is relatively small. In contrast, the Japanese diet does not use oil and fat, contains abundant fermented foods, and consumes seaweed. Japan is known for its longevity, and people think that a well-balanced diet daily is good for preventing and curing illness. In this regard, finding non-disease conditions, so-called "ME-BYO," and curing them before the manifestation of diseases is becoming more common. In this review, we discuss the healthy eating habit, "The Mediterranean-styled Japanese diet," which prevents ME-BYO condition and reduces the risk of various diseases. CONCLUSION: The Mediterranean-styled Japanese diet, a hybrid of Mediterranean and Japanese diets, reduces the risk of various diseases by suppressing chronic inflammation. This nutritional intervention prevents ME-BYO and is beneficial for healthy longevity. Hence, a Mediterraneanstyled Japanese diet might be helpful for healthy longevity in Japan and around the world.

4.
Int J Mol Sci ; 24(15)2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37569540

ABSTRACT

A variety of phytocompounds contained in medical plants have been used as medication, including Kampo (traditional Japanese) medicine. Phytochemicals are one category of the chemical compounds mainly known as antioxidants, and recently, their anti-inflammatory effects in preventing chronic inflammation have received much attention. Here, we present a narrative review of the health-promotion and disease-prevention effects of phytochemicals, including polyphenols, the latter of which are abundant in onions, oranges, tea, soybeans, turmeric, cacao, and grapes, along with the synergetic effects of vitamin D. A phenomenon currently gaining popularity in Japan is finding non-disease conditions, so-called ME-BYO (mibyou) and treating them before they develop into illnesses. In addition to lifestyle-related diseases such as metabolic syndrome and obesity, dementia and frailty, commonly found in the elderly, are included as underlying conditions. These conditions are typically induced by chronic inflammation and might result in multiple organ failure or cancer if left untreated. Maintaining gut microbiota is important for suppressing (recently increasing) intestinal disorders and for upregulating immunity. During the COVID-19 pandemic, the interest in phytochemicals and vitamin D for disease prevention increased, as viral and bacterial infection to the lung causes fatal inflammation, and chronic inflammation induces pulmonary fibrosis. Furthermore, sepsis is a disorder inducing severe organ failure by the infection of microbes, with a high mortality ratio in non-coronary ICUs. However, antimicrobial peptides (AMPs) working using natural immunity suppress sepsis at the early stage. The intake of phytochemicals and vitamin D enhances anti-inflammatory effects, upregulates immunity, and reduces the risk of chronic disorders by means of keeping healthy gut microbiota. Evidence acquired during the COVID-19 pandemic revealed that daily improvement and prevention of underlying conditions, in terms of lifestyle-related diseases, is very important because they increase the risk of infectious diseases. This narrative review discusses the importance of the intake of phytochemicals and vitamin D for a healthy lifestyle and the prevention of ME-BYO, non-disease conditions.


Subject(s)
COVID-19 , Vitamin D , Humans , Aged , Vitamin D/therapeutic use , Pandemics , COVID-19/prevention & control , Vitamins/pharmacology , Inflammation/drug therapy , Anti-Inflammatory Agents , Phytochemicals/pharmacology , Phytochemicals/therapeutic use
5.
Int J Mol Sci ; 24(3)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36768946

ABSTRACT

In recent years, attention has focused on the roles of phytochemicals in fruits and vegetables in maintaining and improving the intestinal environment and preventing metabolic syndrome. A high-fat and high-sugar diet, lack of exercise, and excess energy accumulation in the body can cause metabolic syndrome and induce obesity, diabetes, and disorders of the circulatory system and liver. Therefore, the prevention of metabolic syndrome is important. The current review shows that the simultaneous intake of phytochemicals contained in citruses and grapes together with vitamin D improves the state of gut microbiota and immunity, preventing metabolic syndrome and related diseases. Phytochemicals contained in citruses include polyphenols such as hesperidin, rutin, and naringin; those in grapes include quercetin, procyanidin, and oleanolic acid. The intake of these phytochemicals and vitamin D, along with prebiotics and probiotics, nurture good gut microbiota. In general, Firmicutes are obese-prone gut microbiota and Bacteroidetes are lean-prone gut microbiota; good gut microbiota nurture regulatory T cells, which suppress inflammatory responses and upregulate immunity. Maintaining good gut microbiota suppresses TNF-α, an inflammatory cytokine that is also considered to be a pathogenic contributor adipokine, and prevents chronic inflammation, thereby helping to prevent metabolic syndrome. Maintaining good gut microbiota also enhances adiponectin, a protector adipokine that prevents metabolic syndrome. For the prevention of metabolic syndrome and the reduction of various disease risks, the intake of phytochemicals and vitamin D will be important for human health in the future.


Subject(s)
Metabolic Syndrome , Humans , Metabolic Syndrome/prevention & control , Vitamin D , Intestines , Obesity/metabolism , Prebiotics , Vitamins , Phytochemicals/pharmacology , Phytochemicals/therapeutic use
6.
Article in English | MEDLINE | ID: mdl-31142251

ABSTRACT

BACKGROUND: Grape phytochemicals prevent intestine-related and subsequent other inflammatory diseases. Phytochemicals and vitamin D are useful for the regulation of inflammatory responses. Phytochemicals is the generic name for terpenoids, carotenoids, and flavonoids that consist of a variety of chemicals contained in vegetables and fruits. There are a variety of grape cultivars that contain many kinds of phytochemicals in their skin and seeds. Grape phytochemicals including Grape Seed Extracts (GSE) have already been used to maintain healthy condition through manipulating inflammatory responses by decreasing the expression of inflammation-related factors. DISCUSSION: Grape phytochemicals mainly consist of a variety of chemicals that include terpenoid (oleanolic acid), carotenoids (ß-carotene, lutein), and flavonoids: flavon-3-ols (quercetin), flavan-3-ols (catechins), anthocyanins, oligomers and polymers (tannins and proanthocyanidins), and resveratrol. Phytochemicals improve the dysbiosis (gut microbiota complication) induced by metabolic syndrome and regulate inflammatory diseases induced by TNF-α production. Once absorbed, flavonoids change into glucuronide-form, move into the bloodstream and reach the inflammatory sites including liver, lung, and sites of arteriosclerosis, where they become active. Furthermore, oleanolic acid acts on TGR5 - the cholic acid receptor, as an agonist of cholic acid. These anti-inflammatory effects of phytochemicals have been proven by the experimental animal studies and the clinical trials. CONCLUSION: It is expected the new health food products will be created from grape skins and seeds since grape phytochemicals participate in the prevention of inflammatory diseases like intestine-related inflammatory diseases.


Subject(s)
Inflammation/prevention & control , Intestinal Diseases/prevention & control , Intestines/drug effects , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Vitis/chemistry , Animals , Fruit/chemistry , Gastrointestinal Microbiome/drug effects , Humans , Intestines/microbiology , Intestines/physiopathology , Seeds/chemistry
7.
Article in English | MEDLINE | ID: mdl-30727927

ABSTRACT

BACKGROUND: Production of tumor necrosis factor (TNF)-α by inflammatory cells in lesions is the hallmark of the pathogenesis of rheumatoid arthritis (RA). Regulation of inflammatory responses in knee joints of patients with RA is critical for improving severe symptoms. Flavonoids have inhibitory effects on the acute and chronic inflammatory responses caused by TNF-α. The flavonoid quercetin (QUER) is one of the most prominent dietary antioxidants. OBJECTIVE: The present study investigated the preventive and therapeutic effects of QUER on inflammatory responses in collagen-induced arthritis (CIA) in mice. METHODS: Mice with CIA, a mouse model for RA, were treated with QUER orally three times a week either from the second immunization with collagen (day 21) or day 28 when symptoms of CIA had developed midway. RESULTS: In both cases, inflammation-related clinical scores of knee joints were significantly reduced by treatment with QUER. Histological analyses showed that the representative characteristics of RA, such as damage to interchondral joints, infiltration of inflammatory cells, and pannus formation, were significantly reduced by QUER treatment. Oral administration of QUER significantly decreases lipopolysaccharide (LPS)-induced TNF-α production in a dose-dependent manner. Expression of TNF- α mRNA in knee joints was decreased in QUER-treated mice, compared with those of CIA controls. CONCLUSION: These results suggest that oral administration of QUER might effectively improve symptoms of RA.


Subject(s)
Antioxidants/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Experimental/metabolism , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Quercetin/therapeutic use , Animals , Antioxidants/pharmacology , Arthritis, Experimental/pathology , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred DBA , Quercetin/pharmacology
8.
Article in English | MEDLINE | ID: mdl-27697072

ABSTRACT

BACKGROUND: Our recent findings have demonstrated that electromagnetic radiations (EMR) (1.8 GHz radiofrequency) are able to in vitro induce morphometrical and morphological modifications of human leukocytes from normal donors. METHODS: In view of the evidence that polyphenols exert many beneficial effects on plants, animals and humans, leukocytes from human peripheral blood were pre-treated for 1 h with two polyphenol preparations from red grape before EMR exposure (1.8 GHz). RESULTS: Our data will show that polyphenol pre-treatment reverts to normality the morphology of irradiated leukocytes in comparison to irradiated cells only. Conversely, leukocyte morphometry seems to be not affected by this treatment. CONCLUSION: Here, we demonstrate that polyphenols are also able to normalize leukocyte morphology per se altered before as well as after irradiation. Finally, a working hypothesis aimed at clarifying the protective mechanisms exerted by polyphenols on irradiated leukocytes will be illustrated.


Subject(s)
Cell Shape/radiation effects , Cytoprotection/drug effects , Electromagnetic Radiation , Leukocytes/cytology , Leukocytes/radiation effects , Polyphenols/pharmacology , Radiation Injuries/prevention & control , Adult , Humans , Lymphocyte Count , Radiation Dosage
9.
Curr Pharm Des ; 20(6): 857-63, 2014.
Article in English | MEDLINE | ID: mdl-23701564

ABSTRACT

Type-1 allergic diseases consist of two phases. An inductive phase comprises IgE formation to allergens based on the immune system being biased to predominant T-helper type 2 responses. In a triggering phase allergic symptoms are triggered due to a robust secretion of mediators from mast cells and other cells after re-exposure to the same allergen. Various polyphenols, found in foods and plant sources, have potent anti-allergic activities that have been shown in different disease models and in human clinical trials. The present review summarizes the recent findings and progress in the research about polyphenols and natural products, and their role in allergic diseases. Intake of representative polyphenols (flavones, flavone-3-ols, catechins, anthocyanidins, flavanones, procyanidins, and resveratrol) can improve a skewed Th1/Th2 balance and suppress antigen-specific IgE antibody formation. Oral administration of fermented grape foods (FGF), one example of natural products fermented by lactic acid bacteria, is effective for decreasing allergic symptoms in the effector phase. Inhibitory mechanisms of polyphenols are also discussed.


Subject(s)
Biological Products/therapeutic use , Hypersensitivity, Immediate/therapy , Polyphenols/therapeutic use , Allergens/immunology , Animals , Biological Products/administration & dosage , Diet , Humans , Hypersensitivity, Immediate/immunology , Immune System/immunology , Immunoglobulin E/immunology , Polyphenols/administration & dosage , Polyphenols/isolation & purification , Th1 Cells/immunology , Th2 Cells/immunology
10.
Curr Pharm Des ; 20(6): 864-8, 2014.
Article in English | MEDLINE | ID: mdl-23701568

ABSTRACT

Polyphenols contained in FGM from Negroamaro (N) and Koshu (K) Vitis vinifera have been shown to exhibit several immunomodulating activities. For instance, mice affected by experimental colitis when administered with K-FGM showed an attenuation of the inflammatory process. In murine asthma, K-FGM reduced IgE production and eosinophil number in bronchial alveolar lavage fluid. In vitro, both N- and K-FGM were able to induce T regulatory cells in terms of Foxp-3 molecule expression and release of interleukin-10. In another set of experiments both N- and K-FGM were able to balance rate of proliferation/apoptosis/necrosis of normal human peripheral lymphocytes, thus indicating the property of these compounds to maintain immune homeostatic mechanisms in the host. On the other hand, N- and K-FGM inhibited human basophil degranulation, thus, confirming our previous results obtained with rat basophilic leukemia cells. Finally, N- and K-FGM also decreased oxidative burst of human polymorphonuclear cells and monocytes.Taken together, these findings imply the potential clinical usefulness of FGM administration in inflammatory/allergic conditions, such as chronic asthma.


Subject(s)
Anti-Allergic Agents/pharmacology , Polyphenols/pharmacology , Vitis/chemistry , Animals , Anti-Allergic Agents/isolation & purification , Asthma/drug therapy , Asthma/immunology , Fermentation , Humans , Immunologic Factors/isolation & purification , Immunologic Factors/pharmacology , Inflammation/drug therapy , Inflammation/immunology , Mice , Polyphenols/isolation & purification , Rats
11.
PLoS One ; 8(4): e60078, 2013.
Article in English | MEDLINE | ID: mdl-23565187

ABSTRACT

Lipopolysaccharide (LPS) is recognized by CD14 with Toll-like receptor 4 (TLR4), and initiates 2 major pathways of TLR4 signaling, the MyD88-dependent and TRIF-dependent signaling pathways. The MyD88-dependent pathway induces inflammatory responses such as the production of TNF-α, IL-6, and IL-12 via the activation of NFκB and MAPK. The TRIF-dependent pathway induces the production of type-I IFN, and RANTES via the activation of IRF-3 and NFκB, and is also important for the induction of adaptive immune responses. CD14 plays a critical role in initiating the TRIF-dependent signaling pathway response to LPS, to support the internalization of LPS via endocytosis. Here, we clearly demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS-liposomes) initiate only TRIF-dependent signaling via clathrin-mediated endocytosis, independent of CD14. In fact, LPS-liposomes do not induce the production of TNF-α and IL-6 but induce RANTES production in peritoneal macrophages. Additionally, LPS-liposomes could induce adaptive immune responses effectively in CD14-deficient mice. Collectively, our results strongly suggest that LPS-liposomes are useful as a TRIF-dependent signaling-based immune adjuvant without inducing unnecessary inflammation.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Lipopolysaccharide Receptors/metabolism , Lipopolysaccharides/immunology , Signal Transduction , Animals , Chemokine CCL5/biosynthesis , Clathrin/metabolism , Endocytosis , Endosomes , Epitopes/immunology , Immunoglobulin G/immunology , Interleukin-6/biosynthesis , Lipopolysaccharide Receptors/genetics , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/metabolism , Liposomes , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
12.
Immunopharmacol Immunotoxicol ; 34(5): 815-23, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22963130

ABSTRACT

We previously showed that formation of pulmonary granulomas in mice in response to a mycobacterial glycolipid, trehalose 6,6'-dimycolate (TDM) is due to the action of TNF-α and not of IFN-γ. However, the mechanisms of formation and maintenance of pulmonary granulomas are not yet clear. The purpose of the present study is to evaluate the mechanisms of granuloma formation by TDM at the early phase. Histological analysis showed that inflammatory cells infiltrated the murine pulmonary interstitium on day 2 after an intravenous injection with TDM as a w/o/w emulsion. Clear granuloma formation was observed on day 7 after the injection. The mRNA expression of IL-17, IFN-γ and macrophage inflammatory protein 2 was found in lung mononuclear cells at the day after TDM injection. The major IL-17-producing cells were T-cell receptor (TCR) γδ T cells expressing Vγ6. In mice depleted of γδ T cells by treatment with anti-TCR γδ monoclonal antibody, the number of TDM-induced granuloma was decreased, but the size of granuloma was not affected. Our results suggest that the mycobacterial glycolipid TDM causes activation of IL-17-producing TCR γδ T cells and stimulates chemotaxis of inflammatory cells including neutrophils in to lung.


Subject(s)
Cord Factors/toxicity , Granuloma, Respiratory Tract/immunology , Lung/immunology , Pneumonia/immunology , Receptors, Antigen, T-Cell, gamma-delta , T-Lymphocytes/immunology , Animals , Chemotaxis/drug effects , Chemotaxis/immunology , Cytokines/immunology , Female , Granuloma, Respiratory Tract/chemically induced , Granuloma, Respiratory Tract/pathology , Lung/pathology , Lymphocyte Depletion , Mice , Neutrophil Infiltration/drug effects , Neutrophil Infiltration/immunology , Neutrophils/immunology , Neutrophils/pathology , Pneumonia/chemically induced , Pneumonia/pathology , T-Lymphocytes/pathology , Time Factors
13.
Immunopharmacol Immunotoxicol ; 33(4): 723-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21480758

ABSTRACT

Rheumatoid arthritis (RA) is closely related to the pathogenesis of tumor necrosis factor α in lesions. We investigated the suppressive effects of a Citrus flavanone naringin on inflammatory responses in mice with collagen-induced arthritis (CIA), a mouse model for RA. To investigate potential preventive and therapeutic effects of naringin, mice were given naringin orally three times a week from the second immunization with collagen (day 21) and from day 31, when symptoms of CIA had reached a plateau, respectively. In both cases, inflammation-related clinical scores for knee joints were significantly reduced by administration of naringin. Histological analyses demonstrated that representative phenomena, such as damage to interchondral joints, infiltration of inflammatory cells and pannus formation, were significantly depressed by treatment with naringin. In addition, increases in the expression of high-mobility group box-1 protein in the joints of mice with CIA were suppressed by naringin. These results suggest that oral administration of naringin might be effective for treating human patients with RA.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/prevention & control , Citrus/chemistry , Flavanones/administration & dosage , Administration, Oral , Animals , Anti-Inflammatory Agents/chemistry , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Flavanones/chemistry , Humans , Inflammation/immunology , Inflammation/pathology , Inflammation/prevention & control , Knee Joint/immunology , Knee Joint/pathology , Male , Mice
14.
Curr Top Med Chem ; 11(14): 1767-79, 2011.
Article in English | MEDLINE | ID: mdl-21506932

ABSTRACT

Oxidative stress and inflammatory responses sustained for a long period of time cause many diseases. A proinflammatory cytokine, tumor necrosis factor α (TNF-α), plays a pivotal role in the pathogenesis of chronic and auto-immune diseases. The present review, supplemented by hitherto unpublished data of the authors and their coworkers, shows that the intake of polyphenols contained in natural sources, such as hydroxytyrosol, tyrosol, oleuropein (olives), naringin and hesperidin (Citrus fruits), resveratrol, procyanidins or oligomeric procyanidin (grapes or grape seed extracts), (-)-epigallocatechin gallate (green tea) and quercetin (grapes, green tea) etc., are able to modulate chronic inflammatory diseases, such as type 2 diabetes, rheumatoid arthritis, inflammatory bowel disease, and affect the formation and interaction of advanced glycation end products with their respective receptors. Furthermore, potent activities of fermented grape marc, prepared as a fine lyophilized powder from fresh skin and seeds of a Japanese grape strain (Koshu) and then fermented with Lactobacillus plantarum, are described. Finally, the bioavailability of representative polyphenols will be discussed.


Subject(s)
Antioxidants/therapeutic use , Arthritis, Rheumatoid/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Flavonoids/pharmacology , Inflammatory Bowel Diseases/drug therapy , Phenols/pharmacology , Plant Extracts/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Antioxidants/pharmacokinetics , Arthritis, Rheumatoid/physiopathology , Biological Availability , Diabetes Mellitus, Type 2/physiopathology , Fermentation , Glycation End Products, Advanced/antagonists & inhibitors , Glycation End Products, Advanced/biosynthesis , Humans , Inflammatory Bowel Diseases/physiopathology , Lactobacillus plantarum/metabolism , Mice , Oxidative Stress , Plant Extracts/pharmacology , Polyphenols , Rats , Seeds/chemistry , Tea/chemistry , Tumor Necrosis Factor-alpha/biosynthesis , Vitis/chemistry
16.
Immunopharmacol Immunotoxicol ; 32(4): 593-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20136581

ABSTRACT

We investigated the inhibitory effects of fermented grape marc (FGM), lyophilized fine powder of skin, and seeds of Vitis vinifera Koshu grape prepared by fermentation with Lactobacillus plantarum, on type-I allergic responses in mice. Repeated oral administration of FGM, but not non-fermented grape marc (GM), to BALB/c mice primed with ovalbumin (OVA) resulted in a significant reduction of serum IgE levels, compared with those of immunized controls. After OVA challenge, increased numbers of eosinophils in bronchial alveolar lavage fluids (BALF) significantly decreased by treatment with FGM but not with GM. For passive cutaneous anaphylaxis (PCA) reaction, BALB/c mice received intradermal sensitization with anti-OVA IgE serum and were challenged intravenously with OVA containing Evans blue at 24 h after IgE sensitization. Oral administration of FGM at 30 min before OVA challenge significantly suppressed the PCA reaction. On the other hand, Lactobacillus alone and non-fermented GM did not show any suppressive effects. Interestingly, FGM samples prepared from grapes for red wine, such as Negroamaro (rich in resveratrol) or Tannat (rich in oligomeric procyanidin), did not suppress the reaction. These results indicate that oral administration of FGM, prepared from Koshu grape for white wine but not from grapes for red wine, could suppress both phases of type-I allergic responses. A fraction extractable with acetone was responsible for the suppressive effects of FGM.


Subject(s)
Fermentation , Fruit/microbiology , Hypersensitivity, Immediate/drug therapy , Lactobacillus plantarum , Plant Extracts/therapeutic use , Vitis , Animals , Antibody Formation/drug effects , Antibody Formation/immunology , Asthma/drug therapy , Asthma/immunology , Asthma/prevention & control , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Dose-Response Relationship, Drug , Eosinophils/pathology , Female , Fruit/metabolism , Hypersensitivity, Immediate/immunology , Hypersensitivity, Immediate/prevention & control , Immunoglobulin E/blood , Immunoglobulin E/immunology , Kinetics , Mice , Mice, Inbred BALB C , Ovalbumin/administration & dosage , Ovalbumin/immunology , Passive Cutaneous Anaphylaxis/drug effects , Passive Cutaneous Anaphylaxis/immunology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/pharmacology , Vaccination
17.
Immunopharmacol Immunotoxicol ; 32(3): 454-61, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20100066

ABSTRACT

To investigate the antiallergic effects of fermented grape marc from Negroamaro (N-FGM), we examined antigen (Ag)-induced degranulation of rat basophilic leukemia (RBL-2H3) cells. Among supernatants of N-FGM suspensions in water, ethanol, and dimethyl sulfoxide (DMSO), supernatants of DMSO-suspended N-FGM but not of nonfermented Negroamaro grape marc (N-GM) markedly suppressed the Ag-induced degranulation and phosphorylation of Syk in RBL-2H3 cells. Supernatants of DMSO-suspended N-FGM did not reduce the expression of FcepsilonRI on RBL-2H3 cells. Analyses of supernatants of N-FGM suspensions in water, ethanol, and DMSO by high-performance liquid chromatography revealed higher amounts of quercetin in supernatants of DMSO-suspended N-FGM than those in the other supernatants. Quercetin also suppressed the Ag-induced degranulation and phosphorylation of Syk but did not reduce the expression of FcepsilonRI on RBL-2H3 cells. These results suggest that inhibition of the Ag-induced degranulation and Syk phosphorylation by N-FGM might be due to the action of quercetin, as an active component in N-FGM.


Subject(s)
Anti-Allergic Agents/pharmacology , Basophils/drug effects , Cell Degranulation/drug effects , Quercetin/pharmacology , Vitis/chemistry , Wine , Animals , Anti-Allergic Agents/isolation & purification , Antigens/immunology , Basophil Degranulation Test , Basophils/immunology , Basophils/physiology , Cell Degranulation/immunology , Fermentation , Immunoglobulin E/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Quercetin/isolation & purification , Rats , Syk Kinase , Tumor Cells, Cultured
18.
Immunopharmacol Immunotoxicol ; 31(3): 363-9, 2009.
Article in English | MEDLINE | ID: mdl-19555191

ABSTRACT

Glycosphingolipids (GSLs) are components of the outer membrane of Sphingomonas species, commonly classified into two types, alpha-glucuronosyl ceramide (alpha-GlcACer) and alpha-galacturonosyl ceramide (alpha-GalACer), respectively. GSL-7 from S. yanoikuyae and GSL-13 from S. terrae, with alpha-GalACer-type structure, possess dihydrosphingosine but with a different ratio of C21cyclopropane to C20:1, while other parts remain similar. We therefore examined if this difference in the ratio of C21cyclopropane to C20:1 in the two ceramides may influence activation of, not only invariant natural killer T (iNKT) cells, but also other cells involved in innate immunity. GSL-7 with a large proportion of C21cyclopropane induced stronger activation of iNKT cells, natural killer cells, dendritic cells, and macrophages than GSL-13 with a large proportion of C20:1. The results show that a higher ratio of C21cyclopropane to C20:1 in the dihydrosphingosine molecule allows a more optimal activation of iNKT cells and other cell types.


Subject(s)
Glycosphingolipids/pharmacology , Immunity, Innate/drug effects , Immunologic Factors/pharmacology , Sphingomonas , Animals , Cell Line , Dendritic Cells/immunology , Glycosphingolipids/chemistry , Glycosphingolipids/immunology , Glycosphingolipids/isolation & purification , Immunologic Factors/chemistry , Immunologic Factors/immunology , Immunologic Factors/isolation & purification , Killer Cells, Natural/immunology , Macrophages/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Natural Killer T-Cells/immunology , Structure-Activity Relationship
19.
J Control Release ; 133(1): 18-23, 2009 Jan 05.
Article in English | MEDLINE | ID: mdl-18930085

ABSTRACT

Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-gamma from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes. GSL-liposomes containing DOPE were clearly broken in late endosomes and this may facilitate effective loading of GSLs onto CD1 molecules. Treatment with GSL-liposomes also activated NKT cells and DCs in vivo. Collectively, our results strongly suggest that GSL-liposomes can effectively induce NKT cell-mediated immune responses and may be useful as an immune adjuvant for inducing protective immunity.


Subject(s)
Endosomes/metabolism , Glycosphingolipids/immunology , Lymphocyte Activation/immunology , Natural Killer T-Cells/immunology , Animals , Antigens, CD1d/immunology , Antigens, Ly/analysis , Chloroquine/pharmacology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Endosomes/drug effects , Fatty Acids, Monounsaturated/chemistry , Female , Flow Cytometry , Glycosphingolipids/chemistry , Glycosphingolipids/pharmacology , Interferon-gamma/blood , Interferon-gamma/metabolism , Liposomes/chemistry , Liver/cytology , Liver/drug effects , Liver/immunology , Lymphocytes/immunology , Lymphocytes/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Confocal , NK Cell Lectin-Like Receptor Subfamily B/analysis , Natural Killer T-Cells/chemistry , Phosphatidylethanolamines/chemistry , Quaternary Ammonium Compounds/chemistry , Sphingomonas/chemistry , Spleen/cytology , Spleen/immunology , Toll-Like Receptor 4/genetics
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