Protectin DX Ameliorates Hepatic Steatosis by Suppression of Endoplasmic Reticulum Stress via AMPK-Induced ORP150 Expression.

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.

Anti-inflammatory activity of patchouli alcohol in RAW264.7 and HT-29 cells.

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.

Reduction of matrix metalloproteinase-9 expression by culture filtrate of Paecilomyces farinosus J3.

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.

Protective effect of boldine on dopamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells.

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.