Gallotannins are plant-derived, water-soluble polyphenols with wide-ranging biological activities. Mast cell-mediated allergic inflammation is known to cause many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 with immune regulatory properties. Expression of inflammatory cytokines is mainly regulated by a transcription factor, nuclear factor (NF)-kappaB. In the present study, the effect of eight gallotannins on the level of pro-inflammatory cytokines and NF-kappaB activation was investigated in human mast cell line (HMC-1). HMC-1 cells were sensitized by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). Among the eight gallotannins from EUPHORBIA species, three gallotannins such as 1,2,3,4,6-penta- O-galloyl-beta-D-glucose, 1,2,6-tri-O-galloyl-beta-D-allopyanose, and 1,2,3,6-tetra-O-galloyl-beta-D-allopyranose suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner. In addition, these three gallotannins blocked the activation of NF-kappaB as indicated by an NF-kappaB-dependent gene reporter assay. We conclude that these gallotannins may have potential for the treatment of inflammatory diseases through the down-regulation of NF-kappaB-mediated activation of mast cells.
BackgroundBiyeom-Tang, a medicine prescribed by oriental clinics, has been used for the treatment of the allergic rhinitis (AR). In the present study, an ethanol extract of Biyeom-Tang (EBT) was investigated for anti-allergic properties on bone-marrow derived mast cells (BMMC) and in vivo models.MethodsThe anti-allergic properties of EBT were evaluated by measuring β-Hex release and the production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) on BMMC in vitro and PCA and OVA-induced AR models in vivo.ResultsEBT strongly inhibited a degranulation reaction in a dose dependent manner with an IC50 value of 35.6 μg/ml. In addition, the generation of PGD2 and LTC4 was inhibited in BMMC in a concentration-dependent manner with IC50 values of 7.0 μg/ml and 10.9 μg/ml, respectively. When administrated orally, EBT ameliorated the mast cell-mediated PCA reaction. In the OVA-induced AR model, the increased levels of IgE were reduced by EBT. The levels of cytokines, such as IL-4, IL-5, IL-10, and IL-13 decreased in the splenocytes of EBT-treated mice. The histological analysis shows that the infiltration of inflammatory cells increased by OVA-sensitization was also reduced.ConclusionsTaken together, these results suggested that EBT has anti-allergic and anti-inflammatory effects in vitro and in vivo models.
In this study, tomentosin, a sesquiterpene lactone was isolated from Inulae flos and its biological activities were investigated. The effects of tomentosin on the production of inflammatory mediators as well as on nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW264.7 cells. Tomentosin decreased the production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) by suppressing the protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Additionally, tomentosin reduced the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Tomentosin not only attenuated lipopolysaccharide (LPS)-induced NF-κB activation via the abrogation of inhibitory (I)κBα degradation and caused a subsequent decrease in nuclear p65 level, but it also suppressed the phosphorylation of MAP kinases (p38 and c-Jun N terminal kinase (JNK)). These results indicate that tomentosin exerts anti-inflammatory activities through the inhibition of inflammatory mediators (NO, iNOS, PGE 2 , COX-2, TNF-α, and IL-6) by regulating NF-κB activation and phosphorylation of p38/JNK kinases in macrophages, thus suggesting that tomentosin could be a potential agent for the treatment of inflammatory diseases. Key words tomentosin; inflammatory mediator; nuclear factor (NF)-κB; mitogen-activated protein (MAP) kinaseInflammation is the host response to infection and injury, but if it is left uncontrolled, the inflammatory mediators become involved in the pathogenesis of many inflammatory disorders.1) Macrophages play a crucial role in both the specific and non-specific immune responses to microbial and viral infections. When activated by stimuli such as lipopolysaccharide (LPS), macrophages produce a variety of inflammatory mediators such as prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β) and IL-6.Expression of these inflammatory mediators is regulated by the activation of nuclear factor-kappaB (NF-κB).2) Also, inflammatory mediators including cytokines or mitogenactivated protein (MAP) kinases such as p38 and c-Jun N terminal kinase (JNK) stimulate the pathways by activating the inhibitor κB kinase (IKK).3,4) In unstimulated cells, NF-κB is located in the cytoplasm as an inactive complex bound to its inhibitory protein (IκB). During the process of inflammation, the IKK phosphorylates IκB, inducing its ubiquitination and degradation of IκBα. The free NF-κB then translocates to the nucleus, where it binds to κB-binding sites in the promoter regions of target genes and regulates the expression of various genes, including inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), and inflammatory cytokines. 5-7)Our previous studies have shown that the ethanol extract of Inulae flos is a potent inhibitor of inflammatory mediators. 8)Recently, it was shown that britanin isolated from Inulae flos inhibited the production of inflammatory medi...
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