Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages

Abstract

Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA's anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1α, IL-1β, tumor necrosis factor-α, IFN-β, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-κB and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.

Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21

“…Previous studies suggested that GNA exhibits stronger and broader anti-tumor effects but lower toxicity than gambogic acid (GA), another component of gamboge which has been clinically applied to treat multiple cancers 13 . It has been reported that GNA can induce apoptosis by inactivation of various signaling pathways in human tumors 14 - 16 . Our previous study has revealed that GNA is cytotoxic toward MM cells under normoxic conditions 17 .…”

Neogambogic Acid Suppresses Receptor Activator of Nuclear Factor κB Ligand (RANKL)-Induced Osteoclastogenesis by Inhibiting the JNK and NF-κB Pathways in Mouse Bone Marrow-Derived Monocyte/Macrophages

“…BMMs are considered to be osteoclast precursor cells and can differentiate into osteoclast-like multinucleated cells in vitro via the synergistic actions of RANKL and M-CSF [ 11 , 13 ]. NGA is an active component of Garcinia, which is used in traditional Chinese medicine and has been shown to have a beneficial clinical effect on bone fractures and hemostasis and has been reported to have anti-tumor and anti-inflammatory activities [ 10 , 12 ]. However, the effects of treatment with NGA on osteoporosis has not been investigated before.…”

“…Previous studies have shown that osteoclast activation and differentiation rely on the receptor activator of NF-κB ligand (RANKL)-related signaling pathway, which plays a crucial role in the differentiation of bone marrow-derived monocyte/macrophages (BMMs) into osteoclasts [ 11 ]. In a preliminary experimental study, we found that NGA suppressed a few key proteins in the NF-κB and mitogen-activated protein kinase (MAPK) pathways, which are closely related to the RANKL/RANK pathway [ 12 , 13 ].…”

Modulation of Wnt/β-catenin signaling in IL-17A-mediated macrophage polarization of RAW264.7 cells

“…Macrophages are immune cells that play key roles in inflammatory and maintenance of immune homeostasis. In this regard, macrophages are able to eradicate a variety of pathogenic microorganisms by phagocytosis in the body (1), where they are implicated in the regulation of inflammatory occurrence and development by producing pro-inflammatory/anti-inflammatory factors in response to an infection and/or insult stress (2).…”