Peanut arachidin-1 enhances Nrf2-mediated protective mechanisms against TNF-α-induced ICAM-1 expression and NF-κB activation in endothelial cells.

Arachidin-1 [trans-4-(3-methyl-1-butenyl)-3,5,3',4'-tetrahydroxystilbene] is a polyphenol produced by peanut kernels during germination. The aim of the present study was to investigate the mechanism underlying the anti-inflammatory effect of arachidin-1 in endothelial cells (ECs). The results of cell adhesion and western blotting assays demonstrated that arachidin-1 attenuated tumor necrosis factor (TNF)-α-induced monocyte/EC adhesion and intercellular adhesion molecule-1 (ICAM-1) expression. Arachidin-1 was demonstrated to exert its inhibitory effects by the attenuation of TNF-α-induced nuclear factor-κB (NF-κB) nuclear translocation and inhibitor of κB-α (IκBα) degradation. Furthermore, arachidin-1 upregulated nuclear factor-E2-related factor-2 (Nrf-2), a known mediator of phase II enzyme expression, and increased the transcriptional activity of antioxidant response element. Transfection of ECs with Nrf-2 siRNA blocked the inhibitory effect of arachidin-1 on ICAM-1 expression, NF-κB nuclear translocation and IκBα degradation. In addition, arachidin-1 induced the expression of the phase II enzymes thioredoxin-1, thioredoxin reductase-1, heme oxygenase-1, glutamyl-cysteine synthetase and glutathione S-transferase. Following arachidin-1 pretreatment, the H2O2-induced generation of reactive oxygen species was reduced. Therefore, the present results indicate that arachidin-1 suppresses TNF-α-induced inflammation in ECs through the upregulation of Nrf-2-related phase II enzyme expression.

Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

AIMS: Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. MAIN METHODS: We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. KEY FINDINGS: Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. SIGNIFICANCE: The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells.

[Regulatory effect of leonurus extracts on hyperuricemia in rats].

In this study, SD rats were orally administrated with oteracil potassium (300 mg . kg-1 . d-1 ) to prepare the hyperuricemia model, and divided into normal, model, Allopurinol, LE high dosage, middle dosage and low dose (200, 100, 50 mg . kg-1 . d-1) groups. The rats were orally administrated with test drugs 1 hour later after being orally administrated with Oteracil potassium. After 7 days, serum uric acid, serum creatinine, uric acid and expression of relevant transporters in kidney were tested to study the regulatory effect of leonurus extracts on serum uric acid, renal function and relevant transporters in kidney of rats with hyperuricemia. Compared with the model group, the leonurus extract group could significantly down-regulate serum uric acid and creatinine levels of rats with hyperuricemia, and increase the urine uric acid level. Meanwhile, leonurus extracts could notably down-regulate the mRNA expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), up-regulate the mRNA expressions of organic cation transportanter (OCT) and Carnitine transporter (OCTN) and promote the excretion of uric acid of kidney.

Bioactive protopanaxatriol type saponins isolated from the roots of Panax notoginseng (Burk.) F. H. Chen.

Seven new protopanaxatriol type saponins, 20S-sanchirhinosides A1 (1), A2 (2), A3 (3), A4 (4), A5 (5), and A6 (6), and sanchirhinoside B (7) were obtained as minor constituents from the root extract of Panax notoginseng (Burkill, F. H. Chen), which showed protection effects against antimycin A induced mitochondrial oxidative stress. Their structures were elucidated by chemical and spectroscopic methods (IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compounds 4, 6 and 7 showed significant protective effects against antimycin A-induced L6 cell injury.