Oleuropein Protects Human Retinal Pigment Epithelium Cells from IL-1ß-Induced Inflammation by Blocking MAPK/NF-κB Signaling Pathways.

Proinflammatory mediators such as interleukin (IL)-1ß cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1ß-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1ß induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.

N-acetylcysteine reduces oxidative stress, nuclear factor­κB activity and cardiomyocyte apoptosis in heart failure.

The roles of oxidative stress on nuclear factor (NF)­κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant N­acetylcysteine (NAC). Heart failure was established in Japanese white rabbits with intravenous injections of doxorubicin, with ten rabbits serving as a control group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13 received NAC (NAC group). Cardiac function was assessed using echocardiography and hemodynamic analysis. Myocardial cell apoptosis, apoptosis­related protein expression, NF­κBp65 expression and activity, total anti­oxidative capacity (tAOC), 8­iso­prostaglandin F2α (8­iso­PGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl­2/Bax ratios as well as increased 8­iso­PGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NF­κBp65 and iNOS levels were significantly higher and the P­IκB­α levels were significantly lower in the HF group; expression of all three proteins returned to pre­HF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NF­κBp65 expression and 8­iso­PGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and ­dp/dtmin, respectively) and the Bcl­2/Bax ratio (all P<0.001). The 8­iso­PGF2α levels were positively correlated with LVEDP and negatively correlated with +dp/dtmax and ­dp/dtmin (all P<0.001). The present study demonstrated that NAC increased the antioxidant capacity, decreased the NF­κB activation and reduced myocardial cell apoptosis in an in vivo heart failure model.