Macrophages-involved
inflammation is considered to induce the damage in various diseases. Herein, novel
therapeutics inhibiting over-activation of macrophages could prove an effective strategy to prevent
inflammation-related diseases. Gaudichaudione H (GH), which is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae) has previously been demonstrated its anti-
cancer effects on several
cancer cell lines. However, no report has been published about the anti-inflammatory effect of GH to date. 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, and colon shortening. GH decreased the
protein and
mRNA levels of
IL-6 and TNF-α, iNOS and COX-2
mRNA expression, the activation of NF-κB and MAPK pathways, the phosphorylation of AMPKα and PRAS40, histological damage, and infiltration of macrophages in the colons of mice with DSS-induced
colitis. Taken together, our results support that GH exerts the anti-inflammatory effects in macrophages in vitro through regulation of NF-κB and MAPK pathways, and DSS-induced
colitis mouse model in vivo. These findings suggest that GH may be a promising candidate in treating macrophage-related inflammatory disease.