Gaudichaudione H Inhibits Inflammatory Responses in Macrophages and Dextran Sodium Sulfate-Induced Colitis in Mice

This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, the nuclear translocation of transcription factors NF-κB and activator protein 1 (AP-1), as well as upstream signaling of the toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) pathway in stimulated macrophages. Furthermore, the result of the intracellular signaling array showed that the phosphorylation of adenosine 5'-monophosphate-activated protein kinase-α (AMPKα), proline-rich Akt substrate of 40 kDa (PRAS40), and p38 could be down regulated by GH in BMDMs, indicating that the mechanism by which GH inhibited inflammation may be also associated with the energy metabolism pathway, PRAS40-mediated NF-κB pathway, cell proliferation, apoptosis, and autophagy, etc. In addition, GH alleviated dextran sodium sulfate (DSS)-induced colitis in mice by ameliorating weight loss, stool consistency change, blood in the stool, an...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research