C-Jun N-terminal kinase-mediated anti-inflammatory effects of Garcinia subelliptica in macrophages

Abstract

Garcinia plants have been traditionally used to treat inflammatory diseases, such as skin infections and pain, in many regions including South-East Asia. Garcinia subelliptica, a plant of the Garcinia species widely distributed from Japan to Thailand, has been reported to contain components similar to other Garcinia plants that exhibit anti-inflammatory effects. The present study aimed to explore the anti-inflammatory effects of ethanol extracts of Garcinia subelliptica (EGS) in macrophages, as there are no previous systemic studies that have investigated the effects of Garcinia subelliptica on inflammation. Non-cytotoxic concentrations of EGS (≤200 μg/ml) were observed to reduce nitric oxide production by modulating iNOS expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The expression of cyclooxygenase-2, the enzyme responsible for the production of prostaglandin E2, was notably reduced by EGS. EGS treatment inhibited the production of pro-inflammatory cytokines, including IL-6 and IL-1β, however, not TNF-α. Reduced production of inflammatory mediators by EGS was followed by reduced phosphorylation of c-Jun N-terminal kinase (JNK) however, not of other mitogen-activated protein kinases and nuclear factor-κB. These results indicate that EGS selectively inhibits the excessive production of inflammatory mediators in LPS-stimulated murine macrophages by reducing the activation of JNK, suggesting that EGS is a candidate for modulating severe inflammation.