Galangin의 수지상세포와 미세아교세포 활성화의 억제를 통해 LPS로 유도된 면역 반응 조절

Abstract

Natural compound has been widely used for the treatment of various diseases, such as pneumonia, diarrhea, and hepatitis. Recent studies have demonstrated that natural compounds possess a wide range of pharmacological and biological activities, including anti-inflammatory, anti-microbial, anti-oxidant, and anti-tumor properties. Galangin is a natural compound derived from Alpinia officinarum, and propolis, and has a flanovol backbone. Microglia and denritic cells are originated from myeloid progenitor cells and act as antigen presenting cells in immune system. In previous studies, it has been reported that galangin has an anti-inflammatory effect on RAW 264.7 murine macrophages. However, the effect of galangin on microglial cells and dendritic cells, a kind of phagocytes, is still unknown. In the present study, I demonstrated that inhibitory activity of galangin on BV-2 murine microglial cells and bone marrow-derived dendiritc cells (DCs). I found that galangin decreases nitric oxide (NO) production at non-cytotoxic concentration and the mRNA expression of pro-inflammatory factors such as inducible-NO synthesis (iNOS), NO, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β on lipopolysaccharide (LPS)-stimulated BV-2 cells in a dose-dependent manner. In addition, galangin suppressed the protein expression of iNOS, and the secretion of IL-1β in LPS-activated BV-2 cells. I determined that galangin inhibited the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), p38, and nuclear factor-appa-B (NF-B) and degradation of NF-κB inhibitor (IB-). These results indicated that galangin has anti-neuroinflammatory effect on BV-2 murine microglial cells via inhibition of MAPKs and NF-B activation. I also found that galangin was not cytotixic to DCs and decreases the expression of co-stimulatory molecules such as cluster of differentiation (CD) 80, CD86, major histocompatibility (MHC) I, and MHC II on LPS-stimulated DCs maturation. On DCs, LPS down-regulated the antigen-uptake activity and galangin induced the LPS-decreased phagocytic activity. I ascertain the galangin suppresses the phophorylation of ERK, and JNK in LPS-stimulated DCs. And to determine the inhibitory effect of galangin on LPS-induced DCs maturation in vivo, oral administration of galangin reduced co-stimulatory molecules on splenic DCs of C57BL/6 mice. These results suggested that galangin has an inhibitory effect on LPS induced-DCs maturation through the suppression of ERK and JNK activation. In summary, these findings provide the elucidation of immunopharmacological functions of galangin, and galangin should be considered potential therapeutic adjuvants for excessive immunological reactions and immune-related disease.