ABSTRACT
Fructooligosaccharides (FOS) are prebiotic supplements that can enhance immunological responses in the host to activate mucosal immunity, probably through regulation of gastrointestinal microflora. An area that has not been investigated, however, is the therapeutic potential of prebiotics on allergic airway diseases. The purpose of this study is to evaluate the effects of dietary supplementation with FOS on a murine model of allergic airway inflammation induced by the house dust mite allergen Dermatophagoides farinae (Der f). Male C3H/HeN mice were intratracheally administered with Der f and were fed a diet containing 0% or 2.5% FOS ad libitum. Supplementation with FOS alleviated mite allergen-related airway inflammation characterized by eosinophilic inflammation and goblet cell hyperplasia, which was evidenced by cytological and histological examinations. In addition, the FOS-supplemented diet reduced the serum allergen-specific IgG1 level as compared with a control diet in the presence of the mite allergen. Moreover, FOS tended to suppress the expression of IL-5 and eotaxin in the lungs, which is enhanced by mite allergen. These results suggest that dietary supplementation with FOS can prevent/improve allergic airway inflammation induced by the mite allergen. This effect can be at least partially associated with the inhibition of allergen-specific Ig production and probably with that of IL-5 and eotaxin expression.
Subject(s)
Allergens/toxicity , Antigens, Dermatophagoides/immunology , Diet , Dietary Supplements , Oligosaccharides/therapeutic use , Pyroglyphidae/immunology , Respiratory Hypersensitivity/drug therapy , Administration, Inhalation , Allergens/administration & dosage , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Chemokines/biosynthesis , Cytokines/biosynthesis , DNA/biosynthesis , DNA/genetics , Enzyme-Linked Immunosorbent Assay , Immunoglobulins/biosynthesis , Inflammation/drug therapy , Inflammation/pathology , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred C3H , Respiratory Hypersensitivity/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 microg/body). Dietary supplementation with 1.0 percent CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.
Subject(s)
Cacao/chemistry , Lung Diseases/prevention & control , Proanthocyanidins/pharmacology , Vehicle Emissions/toxicity , Animals , Bronchoalveolar Lavage Fluid/cytology , Catechin/chemistry , Catechin/pharmacology , Cell Adhesion Molecules , Chemokines/biosynthesis , Cytokines/biosynthesis , Immunohistochemistry , Indicators and Reagents , Intubation, Intratracheal , Lipid Peroxidation/drug effects , Lung Diseases/chemically induced , Male , Mice , Mice, Inbred ICR , Oxidative Stress/drug effects , Proanthocyanidins/chemistry , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
BACKGROUND: Metallothionein (MT) is a protein that can be induced by inflammatory mediators and participate in cytoprotection. However, its role in inflammation remains to be established. A study was undertaken to determine whether intrinsic MT protects against acute inflammatory lung injury induced by bacterial endotoxin in MT-I/II knock out (-/-) and wild type (WT) mice. METHODS: MT (-/-) and WT mice were given vehicle or lipopolysaccharide (LPS, 125 microg/kg) intratracheally and the cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, expression of proinflammatory molecules, and nuclear localisation of nuclear factor-kappaB (NF-kappaB) in the lung were evaluated. RESULTS: MT (-/-) mice were more susceptible than WT mice to lung inflammation, especially to lung oedema induced by intratracheal challenge with LPS. After LPS challenge, MT deficiency enhanced vacuolar degeneration of pulmonary endothelial cells and type I alveolar epithelial cells and caused focal loss of the basement membrane. LPS treatment caused no significant differences in the enhanced expression of proinflammatory cytokines and chemokines nor in the activation of the NF-kappaB pathway in the lung between the two genotypes. Lipid peroxide levels in the lungs were significantly higher in LPS treated MT (-/-) mice than in LPS treated WT mice. CONCLUSIONS: Endogenous MT protects against acute lung injury related to LPS. The effects are possibly mediated by the enhancement of pulmonary endothelial and epithelial integrity, not by the inhibition of the NF-kappaB pathway.
Subject(s)
Bronchitis/prevention & control , Endotoxins/toxicity , Metallothionein/therapeutic use , Protective Agents/therapeutic use , Animals , Blotting, Western , Bronchitis/chemically induced , Bronchitis/pathology , Bronchoalveolar Lavage Fluid/chemistry , Cytokines/analysis , Lipid Peroxides/analysis , Lipopolysaccharides/toxicity , MiceABSTRACT
BACKGROUND: Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. OBJECTIVE: The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. METHODS: C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5 mg/mouse/day). RESULTS: Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. CONCLUSION: These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody.
Subject(s)
Cinnamates/administration & dosage , Hypersensitivity/drug therapy , Perilla frutescens , Phytotherapy , Plant Extracts/administration & dosage , Administration, Oral , Allergens , Animals , Depsides , Hypersensitivity/immunology , Male , Mice , Mice, Inbred C3H , Mites , Rosmarinic AcidABSTRACT
The antiulcer activity of cacao liquor water-soluble crude polyphenols (CWSP) was examined. CWSP, alpha-tocopherol, sucralfate (500 mg/kg), and cimetidine (250 mg/kg) were orally administered to male SD rats 30 minutes before ethanol treatment. 5 ml/kg of ethanol given intragastrically caused lesions in mucosa of the glandular stomach. CWSP caused a reduction of such hemorrhagic lesions as well as cimetidine and sucralfate which are typical antiulcer drugs, but alpha-tocopherol was less effective. Thiobarbituric acid reactive substances in gastric mucosa significantly increased with ethanol administration. CWSP treatment significantly reduced this change. The administration of ethanol extensively increased myeloperoxidase (MPO) but not xanthine oxidase (XOD) activity. CWSP reduced the activities of both enzymes; they were considered the main sources of oxygen radicals. According to an in vitro study, CWSP directly reducted XOD but not MPO. These results suggest that the antiulcer mechanism of CWSP was not only radical scavenging but also modulation of leukocyte function.
Subject(s)
Antioxidants/pharmacology , Cacao/metabolism , Ethanol/adverse effects , Flavonoids , Gastric Mucosa/drug effects , Phenols/pharmacology , Polymers/pharmacology , Animals , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Antioxidants/metabolism , Chromatography, High Pressure Liquid , Cimetidine/pharmacology , Cimetidine/therapeutic use , Dose-Response Relationship, Drug , Gastric Mucosa/pathology , Lipid Peroxidation , Male , Peroxidase/antagonists & inhibitors , Peroxidase/metabolism , Phenols/therapeutic use , Polymers/therapeutic use , Polyphenols , Rats , Rats, Sprague-Dawley , Stomach Ulcer/drug therapy , Sucralfate/pharmacology , Sucralfate/therapeutic use , Thiobarbituric Acid Reactive Substances/analysis , Uric Acid/analysis , Vitamin E/pharmacology , Vitamin E/therapeutic use , Xanthine Oxidase/antagonists & inhibitors , Xanthine Oxidase/metabolismABSTRACT
The antioxidative substances contained in cacao liquor, which is one of the major ingredients of chocolate, were separated by column chromatography and high-performance liquid chromatography. Three major compounds were purified and two of them were identified by 1H, 13C NMR and mass spectra as (-)-epicatechin (EC) and (+)-catechin (CA). Their antioxidative activity was measured by monitoring the peroxide value of linoleic acid and the thiobarbituric acid-reactive substance values of erythrocyte ghost membranes and microsomes. EC and CA had strong antioxidative effects in all three methods, but one unidentified peak was found to be less effective. Additionally, we analyzed the polyphenol concentration of cacao liquor extractions produced in several countries. The total polyphenol concentration was 7.0 to 13.0%, catechin concentration was 0.31 to 0.49%, and epicatechin concentration was 0.35 to 1.68% in the extractions. It is believed that chocolate is stable against oxidative deterioration on account of the presence of these polyphenolic compounds, and it is also expected to have a protective role against lipid peroxidation in living systems.
Subject(s)
Alcoholic Beverages/analysis , Antioxidants/isolation & purification , Cacao , Flavonoids , Animals , Antioxidants/pharmacology , Catechin/chemistry , Catechin/isolation & purification , Catechin/pharmacology , Chromatography, High Pressure Liquid , Erythrocyte Membrane/metabolism , Linoleic Acid/metabolism , Lipid Peroxidation/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microsomes, Liver/metabolism , Oxidation-Reduction , Phenols/analysis , Polymers/analysis , Rats , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The antioxidant components of cacao liquor, which is a major ingredient of chocolate, were isolated with column chromatography and high-performance liquid chromatography. Quercetin and its glucoside were identified by spectrometric methods. Clovamide and deoxyclovamide were characterized by (1)H and (13)C NMR and MS spectrometry. Their antioxidative activity was measured by peroxide value of linoleic acid and thiobarbituric acid reactive-substance value of erythrocyte ghost membranes and microsomes. In the bulk oil system, clovamide had the strongest antioxidative activity but was less active in the other experiments. In the case of the two hydrophilic systems, flavans such as quercetin and epicatechin were more potently effective than the glucosides. It is considered that chocolate is stable against oxidative deterioration due to the presence of these polyphenolic compounds.
ABSTRACT
We studied the effects of antioxidants from chocolate, cacao liquor polyphenol (CLP), on human immune functions in vitro. CLP is an enriched polyphenol fraction purified from cacao liquor that is a major component of chocolate. It has been shown that polyphenols have antioxidant activity, and reactive oxygen species (ROS) are involved in immune responses. CLP inhibited both hydrogen peroxide and superoxide anion, typical ROS, production by phorbol myristate acetate-activated granulocytes. CLP also inhibited menadione-induced production of both hydrogen peroxide and superoxide anion in normal human peripheral blood lymphocytes (PBL). CLP treatment of normal PBL in vitro inhibited mitogen-induced proliferation of T cells and polyclonal Ig production by B cells in a dose-dependent manner. CLP treatment inhibited both IL-2 mRNA expression of and IL-2 secretion by T cells. These results suggest that antioxidant CLP has immunoregulatory effects.