ABSTRACT
BACKGROUND: Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study also investigated the effects of 3RS, 7R, 11R-PA on NF-κB activity in order to address the mechanism of its immunomodulatory effects. METHODS: Mouse splenocytes and purified T-cells were stimulated with T-cell mitogens and incubated with 3RS, 7R, 11R-PA, followed by evaluation of IFN-γ production. The effect of 3RS, 7R, 11R-PA on NF-κB activity was also investigated using an A549 cell line with stable expression of an NF-κB-dependent luciferase reporter gene. RESULTS: 3RS, 7R, 11R-PA significantly reduced in vitro IFN-γ production at both the protein and mRNA levels, and was accompanied by decreased expression of T-bet, a key regulator of Th1 cell differentiation. The results indicated that NF-κB-mediated transcriptional activity was significantly decreased by 3RS, 7R, 11R-PA and that GW6471, an antagonist of peroxisome proliferator activated receptor α (PPARα), abrogated the inhibitory effect of 3RS, 7R, 11R-PA on NF-κB activity. CONCLUSIONS: The present study suggests that 3RS, 7R, 11R-PA is a functional and bioactive fatty acid, and has a potentially beneficial effect for amelioration of T-cell mediated autoimmune diseases. This study also indicates that interference in the NF-κB pathway via PPARα activation is a potential mechanism of the immunomodulatory effects of 3RS, 7R, 11R-PA.
Subject(s)
Immunologic Factors/pharmacology , Interferon-gamma/genetics , PPAR alpha/genetics , Phytanic Acid/pharmacology , RNA, Messenger/genetics , T-Lymphocytes/drug effects , A549 Cells , Animals , Cell Differentiation/drug effects , Female , Gene Expression Regulation , Genes, Reporter , Humans , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/immunology , Luciferases/genetics , Luciferases/metabolism , Lymphocyte Activation/drug effects , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/immunology , Oxazoles/pharmacology , PPAR alpha/agonists , PPAR alpha/antagonists & inhibitors , PPAR alpha/immunology , Phytohemagglutinins/antagonists & inhibitors , Phytohemagglutinins/pharmacology , Primary Cell Culture , RNA, Messenger/antagonists & inhibitors , RNA, Messenger/immunology , Signal Transduction , Spleen/cytology , Spleen/drug effects , Spleen/immunology , T-Box Domain Proteins/antagonists & inhibitors , T-Box Domain Proteins/genetics , T-Box Domain Proteins/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/pharmacology , Tyrosine/analogs & derivatives , Tyrosine/pharmacologyABSTRACT
Cryptoquinone, an abietane-type diterpene para-quinone from the bark of Cryptomeria japonica has antifungal and cytotoxic activities, but its biological actions are largely unknown. In this study, we found that para-hydroquinone derivatives inhibited adipocyte differentiation. The actions might have been mediated, at least in part, by activation of the antioxidant-response element induction of phase 2 enzymes and increases in total glutathione.
Subject(s)
Adipocytes/drug effects , Antioxidants/metabolism , Cell Differentiation/drug effects , Diterpenes/chemistry , Hydroquinones/pharmacology , NF-E2-Related Factor 2/metabolism , Response Elements/drug effects , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Animals , Hydroquinones/chemistry , MiceABSTRACT
Green plant-origin electrophilic compounds are a newly recognized class of neuroprotective compounds that provide neuroprotection through activation of the Nrf2/ARE pathway. Electrophilic hydroquinones are of particular interest due to their ability to become electrophilic quinones upon auto-oxidation. Although green plants frequently produce a variety of electrophilic compounds, the detailed mechanisms of action of these compounds remain unknown. Here, we focused on the neuroprotective effects of 11,14-dihydroxy-8,11,13-abietariene (DA1), derived from a para-hydroquinone-type pro-electrophilic compound from the cryptoquinone. DA1 activated the Nrf2/ARE pathway, induced phase 2 enzymes, and increased glutathione, thus protecting neuronal cells from oxidative stress. DA1 had a very broad safety zone (199.41 fold) at least in our system. Thus, DA1 is a novel neuroprotective pro-electrophilic diterpene from green plant.
Subject(s)
Apoptosis/drug effects , Carboxylic Ester Hydrolases/metabolism , Hydroquinones/pharmacology , NF-E2-Related Factor 2/metabolism , Neurons/physiology , Neuroprotective Agents/pharmacology , Oxidative Stress/physiology , Cell Line , Cells, Cultured , Humans , Hydroquinones/chemical synthesis , Neurons/cytology , Neurons/drug effects , Neuroprotective Agents/chemical synthesis , Oxidative Stress/drug effects , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
In our effort to find new whitening agents, we evaluated the effects of representative chalcones [4-hydroxyderricin (1), xanthoangelol (2), xanthoangelol H (3), deoxyxanthoangelol H (4), and deoxydihydroxanthoangelol H (5)] contained in the stem of Angelica keiskei on tyrosinase and melanin formation in B16 melanoma cells. In addition, the antioxidant effects of these chalcones in ORAC and DPPH assays were also determined. Interestingly, all chalcones (1-5) inhibit melanin formation in B16 melanoma cells, with low cytotoxicity.
Subject(s)
Angelica/chemistry , Chalcones/chemistry , Chalcones/pharmacology , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Animals , Cell Line, Tumor , Molecular StructureABSTRACT
Hyperthermostable beta-glucosidase from Pyrococcus furiosus was enclosed in gelatin gel by cross-linking with transglutaminase. Gelatin-immobilized beta-glucosidase was considerably more thermostable than the native enzyme. Lyophilized immobilisate was stored at 90 degrees C for 1 month without loss of activity. The immobilized beta-glucosidase catalyzed transglucosylation of 5-phenylpentanol with 10.0 equivalent of cellobiose at pH 5.0 and 70 degrees C for 12 h to afford 5-phenylpentyl beta-D-glucopyranoside in 41% yield. The immobilized enzyme was more effective than the native one in transglucosylation. The gelatin-immobilized Pfu-beta-glucosidase recovered from the first run of the reaction was reusable on successive runs.
