A hot water extract of Aralia cordata activates bone marrow‐derived macrophages via a myeloid differentiation protein 88‐dependent pathway and protects mice from bacterial infection

Abstract

In traditional Asian medicine, Aralia cordata (AC) is a known as a pain reliever and antiinflammatory drug. Although several of its biological activities have been reported, the immunomodulatory effects of a hot water extract of AC (HAC) have not yet been described. The aim of this study was to investigate whether HAC modulates the activation of macrophages, which play important roles in innate immune responses against microbial pathogens, and if so, to determine the molecular mechanisms by which HAC mediates this process. It was found that HAC activates bone marrow-derived macrophages (BMDM) and increases amounts of nitric oxide and proinflammatory cytokines in a dose-dependent manner. In addition, HAC was found to induce phosphorylation of NF-kB and mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases, extracellular signal-regulated kinases and p38. Interestingly, these effects were absent in BMDM prepared from myeloid differentiation protein 88-knockout mice. Polysaccharides from HAC exerted stronger immunostimulatory effects than HAC itself. Furthermore, orally administered HAC clearly enhanced clearance of the intracellular pathogen Listeria monocytogenes by boosting innate immune responses. These results demonstrate that HAC exerts immunostimulatory effects through the TLR/MyD88 and NF-kB/MAPK signal transduction pathways.

Aralia cordataExtract Activates NF-κB and MAPK Signaling Pathways and Induces Pro-inflammatory Changes in RAW264.7 Macrophages

“…A recent study suggested that exopolysaccharides promote functional and phenotypic activation of macrophages, as evidenced by the ability of the exopolysaccharides to induce morphological changes, stimulate cell activities, and strongly upregulate the production of cytokines, such as TNF-α, IL-1β, IL-6, and IL-12 (30). In a previous study, we determined that polysaccharide isolated from HAC upregulated the innate immune response and L. monocytogenes clearance in vivo (6). In conclusion, our results indicated that HAC promotes the stimulation of monocytes/macrophages and release of proinflammatory cytokines, thereby inducing the immune response.…”

“…Recent studies have highlighted the antinociceptive and anti-inflammatory effects of AC, as well as its protective effect against carbon tetrachloride-induced hepatotoxicity (3)(4)(5). It was also found that the hot water extract of AC (HAC) protected mice from Listeria monocytogenes infection by upregulating the innate immune response (6). The present study was designed to investigate the effect of HAC on the RAW264.7 mouse macrophage which change from an oxidized form (soluble) to a reduced form (insoluble).…”

Ulcer‐healing effects of jumihaidokuto extract in a mouse model of methicillin‐resistant Staphylococcus aureus causing skin infection

“…Listeria monocytogenes were also removed from bacteria-infected mice as AR extracts induce the phosphorylation of NF-κB and mitogen-activated protein kinase (MAPK) [24]. Kikyoto extract, a Kampo formula containing PR and GL, improved staphylococcally induced lung injury [25]. PR extract has been shown to have an antibacterial effect against Porphyromonas gingivalis and a biofilm inhibitory effect against Streptococcus mutans [26].…”

Immunomodulatory activity of mannosylglycerate and two unnatural mannosyl‐oligosaccharides obtained from microbial fermentation on RAW264.7 macrophages

“…Meanwhile, M3-β-1,2 increased the phosphorylation of p38 and ERK, whereas M3-β-1,4 had no obvious effect on the phosphorylation of the three MAPKs. MyD88 is one of the key adaptor molecules that could integrate and relay signals to transcription factors upon activation of pattern recognition receptors (Seo et al, 2016). IRAK-1 belongs to the IL-1 receptorassociated kinases family, and it could associate with MyD88 to activate the nuclear factor kappa-B signaling pathway.…”