Gelam honey exerts anti-inflammatory and antioxidant activities and is thought to have potent effects in reducing infections and healing wounds. The aim of this study was to investigate the effects of intravenously-injected Gelam honey in protecting organs from lethal doses of lipopolysaccharide (LPS). Six groups of rabbits (N = 6) were used in this study. Two groups acted as controls and received only saline and no LPS injections. For the test groups, 1 mL honey (500 mg/kg in saline) was intravenously injected into two groups (treated), while saline (1 mL) was injected into the other two groups (untreated); after 1 h, all four test groups were intravenously-injected with LPS (0.5 mg/kg). Eight hours after the LPS injection, blood and organs were collected from three groups (one from each treatment stream) and blood parameters were measured and biochemical tests, histopathology, and myeloperoxidase assessment were performed. For survival rate tests, rabbits from the remaining three groups were monitored over a 2-week period. Treatment with honey showed protective effects on organs through the improvement of organ blood parameters, reduced infiltration of neutrophils, and decreased myeloperoxidase activity. Honey-treated rabbits also showed reduced mortality after LPS injection compared with untreated rabbits. Honey may have a therapeutic effect in protecting organs during inflammatory diseases.
We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.