Orientin suppresses oxidized low-density lipoproteins induced inflammation and oxidative stress of macrophages in atherosclerosis.

Atherosclerosis is a main reason for peripheral vascular disease. The present study aims to investigate the effects of macrophage foam cells which is an initial part in atherosclerosis. RAW 264.7 were treated with 80 µg/mL oxidized low-density lipoproteins (ox-LDL) to mimic atherosclerosis in vitro. Orientin, a flavonoid from plants, inhibited ox-LDL induced TNFα, IL-6, IL-1ß expression increase. In addition, Orientin also can inhibit the emergence of ox-LDL-induced lipid droplets. The scavenger receptor CD 36 of ox-LDL was significantly downregulated after the treatment of orientin. Inhibition of ROS generation and increasing of eNOS expression by Orientin treatment was used to show the alteration of oxidative stress. Moreover, the expression levels of Angiopoietin-like 2 (angptl2) and NF-κB were significantly upregulated after cells induced by ox-LDL, whereas orientin significantly reversed the effects of ox-LDL. Orientin inhibited ox-LDL-induced inflammation and oxidative stress, and CD36 may be the key regulator during Orientin action.

Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma.

BACKGROUND: Severe injury and associated hemorrhagic shock lead to an inflammatory response and subsequent increased tissue damage. Numerous reports have shown that injury-induced inflammation and the associated end-organ damage is driven by Toll-like receptor 4 (TLR4) activation via damage-associated molecular patterns. We examined the effectiveness of Eritoran tetrasodium (E5564), an inhibitor of TLR4 function, in reducing inflammation induced during hemorrhagic shock with resuscitation (HS/R) or after peripheral tissue injury (bilateral femur fracture, BFF). MATERIAL AND METHODS: Mice underwent HS/R or BFF with or without injection of Eritoran (5 mg/kg body weight) or vehicle control given before, both before and after, or only after HS/R or BFF. Mice were sacrificed after 6 h and plasma and tissue cytokines, liver damage (histology; aspartate aminotransferase/alanine aminotransferase), and inflammation (NF-κB) and gut permeability were assessed. RESULTS: In HS/R Eritoran significantly reduced liver damage (values ± SEM: alanine aminotransferase 9910 ± 3680 U/L versus 1239 ± 327 U/L and aspartate aminotransferase 5863 ± 2000 U/L versus 1246 ± 243 U/L, P < 0.01) at 6 h compared with control when given just before HS and again just prior to resuscitation. Eritoran administration also led to lower IL-6 levels in plasma and liver and less NF-κB activation in liver. Increases in gut barrier permeability induced by HS/R were also prevented with Eritoran. Eritoran similarly diminished BFF-mediated systemic inflammatory responses. CONCLUSION: These data suggest Eritoran can inhibit tissue damage and inflammation induced via TLR4/myeloid differentiation factor 2 signaling from damage-associated molecular patterns released during HS/R or BFF. Eritoran may represent a promising therapeutic for trauma patients to prevent multiple organ failure.