Aims To investigate anti‐inflammatory effects of Lactobacillus reuteri LM1071 in lipopolysaccharides (LPS)‐induced inflammation RAW264.7 cells. Methods and Results To evaluate anti‐inflammatory activities of L. reuteri LM1071, LPS‐stimulated RAW264.7 cells were used. Gene expression levels of eight immune‐associated genes including IL‐1β, IL‐6 and TNF‐α and protein production levels of COX‐1 and COX‐2 were analysed. Moreover, the production of eicosanoids as important biomarkers for anti‐inflammation was determined. Conclusions The current study demonstrates that L. reuteri LM1071 has anti‐inflammatory potential by inhibiting the production of inflammation mediators such as NO, eicosanoids such as PGE1 & PGE2, pro‐inflammatory cytokines and COX proteins. It can also enhance the production of inflammatory associated genes such as IL‐11, BMP4, LEFTY2 and EET metabolite. Significance and Impact of the Study Lactobacillus reuteri is one of the crucial bacteria for food fermentation. It can be found in the gastrointestinal system of human and animals. Several studies have shown that L. reuteri has valuable effects on host health. The current study firstly demonstrated that L. reuteri has a beneficial effect on the inflammation containing the variation of eicosanoids (PGE1 and PGE2) which are one of the most important biomarkers and moreover eicosanoid‐associated genes as well as proteins (COX‐2).

Arachidonic acid (ARA) is an integral constituent of the biological cell membrane, conferring it with fluidity and flexibility, which are necessary for the function of all cells, especially nervous system, skeletal muscle, and immune system. Codium species biosynthesize sulfated polysaccharides with very distinct structural features. Some of them have different biological activities with great potential in pharmaceutical applications. In this study, anionic macromolecules extracted from Codium fragile were investigated for their cooperative immuneenhancing activities with ARA. The cooperation between ARA and Codium resulted in increased, dose-dependent nitric oxide production and iNOS gene expression. In addition, co-treatment of ARA and Codium effectively increased pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), compared with Codium alone. We also demonstrated that the expression of COX-2 mRNA was also increased, which is responsible for the production of inflammatory mediator prostaglandins and their metabolites. Compared to the Codium group, the co-treatment of Codium with ARA enhanced the phosphorylation of nuclear factor-κB p-65, p38, and extracellular signal-related kinase 1/2, indicating that this combination stimulated immune response through nuclear factor-κB and mitogen-activated protein kinase pathways. These results indicated that the coordination of arachidonic acid with polysaccharide extracted from seaweed may be a potential source of immunomodulatory molecules.

Tunicates are known to contain biologically active materials and one species in particular, the sea peach ( Halocynthia aurantium ), has not been thoroughly studied. In this study we aimed to analyze the fatty acids profile of the H. aurantium body wall and its immunomodulatory effects on RAW264.7 macrophage-like cells. The fatty acids were classified into three categories: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Omega-3 fatty acid content, including EPA and DHA, was higher than omega-6 fatty acids. H. aurantium body wall fatty acids exhibited enhanced immune response and anti-inflammatory effects on RAW264.7 macrophage-like cells. Under normal conditions, fatty acids significantly increase nitric oxide (NO) and PGE 2 production in a dose-dependent manner, thereby improving the immune response. On the other hand, in LPS-treated RAW264.7 cells, fatty acids significantly decreased nitric oxide (NO) and PGE 2 production in a dose-dependent manner, thereby enhancing anti-inflammatory effects. Fatty acids transcriptionally control the expression of the immune-associated genes, iNOS, IL-1β, IL-6, COX-2 , and TNF-α , via the MAPK and NF-κB signaling cascades in RAW264.7 cells. However, in LPSstimulated RAW264.7 cells, H. aurantium body wall fatty acids significantly inhibited expression of inflammatory cytokine; similarly, production of COX-2 and PGE 2 was inhibited. The results of our present study provide insight into the immune-improving and anti-inflammatory effects of H. aurantium body wall fatty acids on macrophages. In addition, our study demonstrates that H. aurantium body wall is a potential source of immune regulatory components.

Ginseng, a commonly used medicinal herb, contains polysaccharide as one of the bioactive compounds. This study aimed at evaluating the immune enhancement effects of Korean ginseng berry polysaccharides (GBPs) on macrophage RAW264.7 cells and their chemical characteristics. The crude polysaccharide (GBP-C) was extracted and fractionated to different polysaccharides (GBP-F1, GBP-F2, and GBP-F3). GBPs were mainly composed of rhamnose, arabinose, mannose, glucose and galactose, with molecular weights (M w ) ranging from 16 × 10 3 to 328 × 10 3 g/mol. While all the GBPs significantly increased the NO production in a dosedependent manner, GBP-F2 showed the highest immuneenhancing effects. GBP-F2 up-regulated the mRNA expression of iNOS, IL-1β, IL-6, IL-10, and TNF-α through activating phosphorylation of NF-κB-p65, ERK1/2, JNK, and p38 to a greater extent than the other GBPs samples. These results indicate that GBPs, and especially GBP-F2, have strong immune enhancement effects desirable for application in the food and pharmaceutical industries.

Panax ginseng C. A. Meyer is well known as traditional herbal medicine, and ginseng berries are known to exhibit potential immune-enhancing functions. However, little is known about the in vivo immunomodulatory activity of Korean ginseng berries. In this study, crude Korean ginseng berries polysaccharides (GBP) were isolated and their immunomodulatory activities were investigated using cyclophosphamide (CY)-induced immunosuppressive BALB/c mice. In CY-treated mice, oral administration of GBP (50-500 mg/kg BW) remarkably increased their spleen sizes and spleen indices and activated NK cell activities. GBP also resulted in the proliferation of splenic lymphocytes (coordinating with ConA: plant mitogen which is known to stimulate T-cell or LPS: endotoxin which binds receptor complex in B cells to promote the secretion of pro-inflammatory cytokines) in a dose-dependent manner. In addition, GBP significantly stimulated mRNA expression levels of immune-associated genes including interleukin-1β ( IL-1β ), IL-2 , IL-4 , IL-6 , tumor necrosis factor-α ( TNF-α ), interferon-γ ( IFN-γ ), toll-like receptor 4 ( TLR-4 ), and cyclooxygenase-2 ( COX-2 ) in CY-treated mice. These results indicate that GBP is involved in immune effects against CY-induced immunosuppression. Thus, GBP could be developed as an immunomodulation agent for medicinal or functional food application.