lucidone and Inflammation

Here, we investigated the anti-inflammatory activity of lucidone, a phytocompound isolated from the fruits of Lindera erythrocarpa Makino, against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice. Male ICR mice were injected intraperitoneally with LPS (5 microg/kg), and the effects of pretreatment with various concentrations of lucidone (50-200 mg/kg) for 12h on the formation of nitric oxide (NO), prostaglandin-E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) were analyzed. Lucidone inhibited the production of NO, PGE(2) and TNF-alpha production in LPS-induced mice, and also induced mRNA and protein levels of inducible nitric oxide synthase (iNOS), and cyclooxigenase-2 (COX-2). The two common response elements of the iNOS and COX-2 genes are nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). NF-kappaB nuclear translocation and DNA binding were inhibited by lucidone in the LPS-induced mice. Moreover, lucidone decreased the expression and phosphorylation of c-Jun N-terminal kinase (JNK) protein thereby causing the subsequent inhibition of AP-1 activity. Finally, our results indicated that lucidone was able to block mitogen-activated protein kinases activity and its downstream signaling activation of NF-kappaB and AP-1. We thus conclude that lucidone exerts its anti-inflammatory effects in mice by inhibiting the expression of pro-inflammatory factors and their related signaling pathways.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Blotting, Western; Cyclooxygenase 2 Inhibitors; Cyclopentanes; Dinoprostone; Electrophoretic Mobility Shift Assay; I-kappa B Kinase; Inflammation; Lindera; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Reverse Transcriptase Polymerase Chain Reaction; RNA; Signal Transduction; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

In this study, in vitro and in vivo antiinflammatory activities of fruits from Lindera erythrocarpa Makino were evaluated. The ethyl acetate soluble fraction derived from the ethanol extract of L. erythrocarpa fruits inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS) induced NO in the murine macrophage cell line (RAW264.7) assay, the EC(50) being 16.35 microg/mL. Four compounds, including lucidone (1), cis/trans-methylludicone (2), methyl linderone (3) and linderone (4) were identified from the active fraction based on the bioactivity-guided fractionation procedure. Of these lucidone possessed the strongest NO inhibitory activity with an EC(50) value of 4.22 microg/mL. Furthermore, results from the protein expression assay demonstrated that lucidone suppressed iNOS and COX-2 protein expression in a dose-dependent manner. Lucidone also provided antiinflammatory activity in the croton oil-induced ear edema assay. When it was applied topically at a dosage of 0.5 and 1 mg per ear, the percent edema reduction in treated mice was 44% and 25%, respectively. The results obtained in this study indicated that lucidone has a good potential to be developed as an antiinflammation agent.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Croton Oil; Cyclopentanes; Dose-Response Relationship, Drug; Edema; Fruit; Inflammation; Lindera; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Molecular Structure; Nitric Oxide; Phytotherapy; Plant Extracts