11-O-acetylcyathatriol inhibits MAPK/p38-mediated inflammation in LPS-activated RAW 264.7 macrophages and has a protective effect on ethanol-induced gastric injury

Abstract

The present study investigated the effects of 11-O-acetylcyathatriol, a natural cyathane diterpene, on the release of inflammatory mediators and on the activation of the nuclear factor (NF)-κB or the mitogen‑activated protein kinase (MAPK) transduction pathways in lipopolysaccharide (LPS)-activated macrophages. MTT was used to evaluate the cytotoxicity. A Griess assay was used to determine the production of nitrous oxide (NO). The levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 were determined using ELISA kits. The protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, phosphorylated (p)‑extracellular signal‑regulated kinase (ERK1/2), p‑J‑N‑terminal kinase (JNK), p‑p38 and inhibitor of NFκB (IκB)‑α were detected using western blot analysis. 11‑O‑acetylcyathatriol significantly inhibited the overproduction of NO and the release of IL‑6, but had no inhibitory effect on the release of TNF‑α. It also significantly downregulated the high expression levels of iNOS and COX‑2 induced by LPS. In addition, it markedly inhibited the phosphorylation of the MAPK/p38 protein, but only exhibited weak inhibition on the phosphorylation of the ERK1/2 and JNK proteins, and the degradation of the IκB‑α protein. The possible protective effect of 11‑O‑acetylcyathatriol on ethanol‑induced gastric injury was also examined using an in vivo animal experiment. Following gavage administration, it showed an important protective effect on ethanol‑induced gastric mucosal injury in rats. These results suggested the possibility that the anti‑inflammatory effect of 11‑O‑acetylcyathatriol was predominantly due to the inhibition of iNOS and COX‑2 proteins, and may be associated with the MAPK/p38 transduction pathway, but not the NF‑κB transduction pathway. These findings provide an explanation for the underlying mechanism of anti-inflammatory action of 11-O-acetylcyathatriol, which may assist with its clinical application and future development.

Ascofuranone inhibits lipopolysaccharide–induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophages

“…It was previously reported that mitogen-activated protein kinase (MAPK) signaling pathways are related to LPS-activated iNOS and COX-2 expression in macrophages; these are considered the classical pathways that regulate the inflammatory response [ 24 – 26 ]. Activation of MAPK pathways causes releases of inflammatory factors and initiates an oxidative stress response, consequently accelerating the inflammatory process.…”

Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells

“…It is well clarified that mitogen-activated protein kinase ERK or NFκB transduction pathways are majorly involved in LPS-induced macrophages inflammation [ 33 ]. ERK pathway may be taken as intermediate stage in the regulation of NF-κB activation [ 34 , 35 ].…”

Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways

“…Inflammation is a physiological and immunological response triggered by both cell and tissue injury that is primarily controlled by a MAPK cascade signaling pathway [ 36 ]. MAPKs are kinases that are responsible for most cellular responses to inflammatory cytokines and external stress signals, and these kinases are essential for the regulation of the production of various inflammation mediators [ 37 , 38 ]. MAPK cascade pathway is activated by inflammatory stimuli such as LPS.…”