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1.
J Pharmacol Exp Ther ; 365(3): 485-493, 2018 06.
Article in English | MEDLINE | ID: mdl-29572342

ABSTRACT

Docosahexaenoic acid (DHA) and its bioactive compounds may have suppressive effects on inflammation, endoplasmic reticulum (ER) stress, and insulin resistance. Protectin DX (PDX), a double lipoxygenase product from DHA has shown a suppressive effect on inflammation and insulin resistance. However, the effects of PDX on ER stress and hepatic steatosis have not been elucidated yet. Herein we report that PDX could stimulate the AMP-activated protein kinase (AMPK) phosphorylation, thereby upregulating oxygen-regulated protein 150 (ORP150) expression in a dose-dependent manner. Treatment of HepG2 cells with PDX attenuated the palmitate-induced triglyceride accumulation through regulation of the sterol regulatory element-binding protein 1 (SREBP1)-mediated pathway. To deal with the pharmacological significance in the protective effects of PDX on hepatic steatosis, we performed in vivo experiments. In a mouse model, the PDX administration would alleviate the high-fat diet-induced hepatic steatosis and trigger the hepatic AMPK phosphorylation and ORP150 expression. PDX improved palmitate-induced and HFD-induced impairment of hepatic lipid metabolism and steatosis through suppression of ER stress via an AMPK-ORP150-dependent pathway.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Docosahexaenoic Acids/pharmacology , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation/drug effects , HSP70 Heat-Shock Proteins/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Animals , Docosahexaenoic Acids/therapeutic use , Hep G2 Cells , Humans , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Phosphorylation/drug effects , Triglycerides/metabolism
2.
Int J Mol Med ; 35(1): 187-94, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25406033

ABSTRACT

In order to evaluate whether the aqueous fraction of Cinnamomum cassia produced by solid-state fermentation with Phellinus baumii (afCc/Pb) inhibits atopic symptoms in vivo, its efficacy was evaluated in an animal model of 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis. Immune-related cells were quantified using hematoxylin and eosin staining, and phenotypic cytokines, enzymes and the expression of other proteins in the animal model were evaluated. The data revealed that afCc/Pb (100 µg/ml) exhibited strong anti-atopic activity, causing a significant 40% reduction in immune response, as shown by the extent of ear swelling, resulting from a decrease in the number of eosinophils in the skin tissues due to decreased matrix metalloproteinase-2 and interleukin-31 expression. These results collectively suggest that afCc/Pb has the potential to alleviate the symptoms of atopic dermatitis in a mouse model of DNFB-induced atopic dermatitis, and that it may be a valuable bioresource for the cosmetic/cosmeceutical industry.


Subject(s)
Basidiomycota , Cinnamomum aromaticum/chemistry , Dermatitis, Atopic/drug therapy , Fermentation , Plant Bark/chemistry , Plant Extracts/pharmacology , Animals , Cytokines/metabolism , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/pathology , Disease Models, Animal , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Mice , Plant Extracts/administration & dosage
3.
Exp Gerontol ; 53: 57-66, 2014 May.
Article in English | MEDLINE | ID: mdl-24594315

ABSTRACT

The root of Panax ginseng improves testicular function both in humans and animals. However, the molecular mechanism by which ginseng exerts this effect has not been elucidated. Changes in protein expression in the rat testis in response to a pectinase-treated P. ginseng extract (GINST) were identified using 2-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF MS. Number of sperm, Sertoli cells and germ cells, and the Sertoli Cell Index decrease in the testis of aged rats (AR) relative to young control rats (YCR). However, those parameters were completely restored in GINST-treated AR (GINST-AR). A proteomic analysis identified 14 proteins that were differentially expressed between vehicle-treated AR (V-AR) and GINST-AR. Out of these, the expression of glutathione-S-transferase (GST) mu5 and phospholipid hydroperoxide (PH) glutathione peroxidase (GPx) was significantly up-regulated in GINST-AR compared to V-AR. The activity of GPx and GST, as well as the expression of glutathione, in the testis of GINST-AR was higher than that in V-AR. The levels of lipid peroxidation (LPO) increased in AR compared with YCR, but this change was reversed by GINST-AR. These results suggest that the administration of GINST enhances testicular function by elevating GPx and GST activity, thus resulting in increased glutathione, which prevents LPO in the testis.


Subject(s)
Aging/physiology , Panax , Phytotherapy/methods , Testis/drug effects , Aging/drug effects , Aging/pathology , Animals , Antioxidants/metabolism , Chromatography, High Pressure Liquid/methods , Drug Evaluation, Preclinical/methods , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Gonadal Steroid Hormones/blood , Lipid Peroxidation/drug effects , Male , Oxidation-Reduction , Plant Extracts/pharmacology , Polygalacturonase , Proteome/metabolism , Rats , Rats, Sprague-Dawley , Sperm Motility/drug effects , Spermatogenesis/drug effects , Spermatogenesis/physiology , Testis/metabolism , Testis/pathology , Testis/physiopathology
4.
Food Chem Toxicol ; 55: 229-33, 2013 May.
Article in English | MEDLINE | ID: mdl-23348408

ABSTRACT

Patchouli alcohol (PA) is a chemical compound extracted from patchouli which belongs to the genus Pogostemon, herb of mint family. Recently, it has been reported that PA inhibits the production of inflammatory mediators. However, the biological mechanisms of PA for anti-inflammatory activities have not been studied. In this study, we investigated whether PA decreases the production of inflammatory mediators through downregulation of the NF-κB and ERK pathway. Our data indicated that PA inhibits the over-expression of iNOS and IL-6 in protein and mRNA levels in LPS-stimulated RAW264.7 and TNF-α stimulated HT-29 cells. PA inhibited IκB-α degradation and p65 nuclear translocation, and subsequently suppressed transcriptional activity of NF-κB in LPS-stimulated RAW264.7 and TNF-α-stimulated HT-29 cells. In addition, PA inhibited LPS- or TNF-α-stimulated ERK1/2 activation by decreasing phosphorylation of ERK1/2. These findings suggest that PA shows anti-inflammatory activities through suppressing ERK-mediated NF-κB pathway in mouse macrophage and human colorectal cancer cells.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Sesquiterpenes/pharmacology , Animals , Base Sequence , Cell Line , DNA Primers , HT29 Cells , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , NF-kappa B/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/pharmacology
5.
Exp Ther Med ; 4(5): 820-824, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23226733

ABSTRACT

To determine whether aqueous and ethanol fractions of the Angelica keiskei leaf exert toxicity when used for cosmetic purposes, we performed the acute eye irritancy test. Animals were treated with sample fractions (100 mg/dose) according to standard procedure guidelines. No significant changes or damage was detected in the fraction-treated groups in terms of ocular lesions in the cornea, the size of the cornea with turbidity, swelling of the eyelid and emission discharge. However, sodium dioctyl sulfosuccinate, a positive control, induced severe toxic symptoms. Thus, aqueous and ethanol fractions of Angelica keiskei do not appear to induce acute toxicity in the eye lens, as assessed from anatomical and pathological observations in the rabbit eye. Our results collectively suggest that aqueous and ethanol fractions show promise as cosmetic ingredients that do not cause eye toxicity.

6.
Exp Ther Med ; 2(2): 357-362, 2011 Mar.
Article in English | MEDLINE | ID: mdl-22977510

ABSTRACT

The aim of the present study was to investigate the anti-tumor effects of a culture filtrate of Paecilomyces farinosus J3. Various anti-tumor assays using B16 melanoma cells were carried out. Paecilomyces farinosus J3 significantly decreased the wound healing capability, invasiveness and angiogenic activity, which was confirmed by wound healing, human umbilical vein endothelial cell and invasion assays. Paecilomyces farinosus J3 strongly inhibited cell migration, tube formation and the angiogenic process in a concentration-dependent manner. Zymographic analysis also indicated a reduced expression of matrix metalloproteinase-9 (MMP-9), a 92-kDa gelatinase. Taken together, the results indicate that the anti-tumor activities of Paecilomyces farinosus J3 originate from the reduction of MMP-9 expression in B16F10 cells.

7.
Biochem Pharmacol ; 63(3): 495-505, 2002 Feb 01.
Article in English | MEDLINE | ID: mdl-11853700

ABSTRACT

Boldine ([S]-2,9-dihydroxy-1,10-dimethoxyaporphine) has been shown to exert antioxidant and anti-inflammatory effects. The present study elucidated the protective effect of boldine on catecholamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Dopamine (200 microM) and 6-hydroxydopamine (6-OHDA, 100 microM) attenuated Ca(2+) and succinate-induced mitochondrial swelling and membrane potential formation. Boldine (10-100 microM) and 10 microg/mL of superoxide dismutase (SOD) or catalase reduced the effect of catecholamine oxidation on brain mitochondria. Boldine, SOD, and catalase decreased catecholamine-induced mitochondrial cytochrome c release. Antioxidant enzymes attenuated the depressant effect of catecholamines on mitochondrial electron flow, whereas boldine did not reduce it. Boldine inhibited the catecholamine-induced decrease in thioredoxin reductase activity and the increase in thiol oxidation in mitochondria. It also showed a scavenging action on hydrogen peroxide and hydroxyl radicals and decreased the formation of melanin from dopamine. Boldine and antioxidant enzymes decreased the dopamine-induced cell death, including apoptosis, in PC12 cells. The results suggest that boldine may attenuate the catecholamine oxidation-induced brain mitochondrial dysfunction and decrease the dopamine-induced death of PC12 cells through a scavenging action on reactive oxygen species and inhibition of melanin formation and thiol oxidation.


Subject(s)
Aporphines/pharmacology , Dopamine/pharmacology , Mitochondria/drug effects , Animals , Brain/drug effects , Brain/metabolism , Catecholamines/metabolism , Cell Membrane Permeability/drug effects , Cell Survival/drug effects , Cytochrome c Group/metabolism , Drug Interactions , Electron Transport/drug effects , Free Radical Scavengers/metabolism , Melanins/metabolism , Mitochondria/physiology , Neurons/drug effects , Neurons/metabolism , PC12 Cells , Rats , Reactive Oxygen Species/metabolism , Sulfhydryl Compounds/metabolism , Thioredoxin-Disulfide Reductase/metabolism
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