10 research outputs found
Whiskey Congeners Suppress LPS/IFNγ-Induced NO Production in Murine Macrophage RAW 264 Cells by Inducing Heme Oxygenase‑1 Expression
Whiskey includes many nonvolatile substances (whiskey
congeners;
Whc) that seep from the oak cask during the maturation process. To
date, many functions of Whc have reported, such as antiallergy and
antimelanogenesis. This study examined the effect of Whc on LPS/IFNγ-induced
nitric oxide (NO) production in murine macrophage RAW 264 cells. Whc
suppressed LPS/IFNγ-induced NO production in a concentration-dependent
manner. To determine the active compounds in Whc, the effect of 10
major compounds isolated from Whc on LPS/IFNγ-induced NO production
was examined. Coniferylaldehyde (CA) and sinapylaldehyde (SiA) strongly
suppressed LPS/IFNγ-induced NO production. Pretreatment with
Whc, CA, and SiA induced heme oxygenase-1 (HO-1) expression. The expression
of HO-1 by Whc, CA, and SiA pretreatment was due to activation of
Nrf2/ARE signaling via the elevation of intracellular reactive oxygen
species. To investigate the in vivo effects of Whc, Whc was administered
to mice with antitype II collagen antibody-induced arthritis, and
we the arthritis score and hind paw volume were measured. Administration
of Whc remarkably suppressed the arthritis score and hind paw volume.
Taken together, these findings suggest that Whc is beneficial for
the treatment of inflammatory disease
Identification of a New Mutagenic Polychlorinated Biphenyl Derivative in the Waka River, Wakayama, Japan, Showing Activation of an Aryl Hydrocarbon Receptor-Dependent Transcription
Chemical Synthesis of a Novel Aromatic Amine Mutagen Isolated from Water of the Nishitakase River in Kyoto and a Possible Route of Its Formation
The Steroidal Alkaloid Tomatidine and Tomatidine-Rich Tomato Leaf Extract Suppress the Human Gastric Cancer-Derived 85As2 Cells In Vitro and In Vivo via Modulation of Interferon-Stimulated Genes
The steroidal alkaloid tomatidine is an aglycone of α-tomatine, which is abundant in tomato leaves and has several biological activities. Tomatidine has been reported to inhibit the growth of cultured cancer cells in vitro, but its anti-cancer activity in vivo and inhibitory effect against gastric cancer cells remain unknown. We investigated the efficacy of tomatidine using human gastric cancer-derived 85As2 cells and its tumor-bearing mouse model and evaluated the effect of tomatidine-rich tomato leaf extract (TRTLE) obtained from tomato leaves. In the tumor-bearing mouse model, tumor growth was significantly inhibited by feeding a diet containing tomatidine and TRTLE for 3 weeks. Tomatidine and TRTLE also inhibited the proliferation of cultured 85As2 cells. Microarray data of gene expression analysis in mouse tumors revealed that the expression levels of mRNAs belonging to the type I interferon signaling pathway were altered in the mice fed the diet containing tomatidine and TRTLE. Moreover, the knockdown of one of the type I interferon-stimulated genes (ISGs), interferon α-inducible protein 27 (IFI27), inhibited the proliferation of cultured 85As2 cells. This study demonstrates that tomatidine and TRTLE inhibit the tumor growth in vivo and the proliferation of human gastric cancer-derived 85As2 cells in vitro, which could be due to the downregulation of ISG expression
Isolation and Chemical−Structural Determination of a Novel Aromatic Amine Mutagen in Water from the Nishitakase River in Kyoto
Isolation and Identification of a New 2-Phenylbenzotriazole-Type Mutagen (PBTA-3) in the Nikko River in Aichi, Japan
Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway
3β-Hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) were recently detected in human atherosclerotic tissues and brain specimens, and they may play pivotal roles in the pathogenesis of atherosclerosis and neurodegenerative diseases. However, as their origin remains unidentified, we examined the formation mechanism, the stability, and the fate of secosterols in vitro and in vivo. About 40% of secosterol-A remained unchanged after 3 h incubation in the FBS-free medium, whereas 20% and 40% were converted to its aldehyde-oxidation product, 3β-hydroxy-5-oxo-secocholestan-6-oic acid, and secosterol-B, respectively. In the presence of FBS, almost all secosterol-A was converted immediately to these compounds. Secosterol-B in the medium, with and without FBS, was relatively stable, but ∼30% was converted to its aldehyde-oxidation product, 3β-hydroxy-5β-hydroxy-B-norcholestane-6-oic acid (secoB-COOH). When neutrophil-like differentiated human leukemia HL-60 (nHL-60) cells activated with PMA were cultured in the FBS-free medium containing cholesterol, significantly increased levels of secosterol-A and its aldehyde-oxidation product, but not secosterol-B, were formed. This secosterol-A formation was decreased in the culture of PMA-activated nHL-60 cells containing several reactive oxygen species (ROS) inhibitors and scavengers or in the culture of PMA-activated neutrophils isolated from myeloperoxidase (MPO)-deficient mice. Our results demonstrate that secoterol-A is formed by an ozone-like oxidant generated with PMA-activated neutrophils through the MPO-dependent mechanism