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.