Drugs, Cosmetics and Chemicals Development Center, Hayashibara Biochemical Laboratories, Inc., Japan.
J Ethnopharmacol. 2011 Mar 24;134(2):450-9. doi: 10.1016/j.jep.2010.12.041. Epub 2011 Jan 7.
Tryptanthrin is a compound isolated from Polygonum tinctorium, which is a known folk medicine with various biological activities.
Allergic diseases are initiated by the development of allergen-specific T helper type 2 (Th2) cells and amplified by the degranulation of and cytokine release from basophils and mast cells during an effector phase. We found that Tryptanthrin could down-regulate IL-4 production by Th2 cells, while IFN-γ production by Th1 cells was not affected. Since IL-4 produced by basophils and effector Th2 cells has been shown to play important roles in the development and amplification of Th2-dominated allergic responses, we examined the effects of Tryptanthrin on the initiation and effector phase responses of Type I allergy in vitro.
To determine the mechanisms of Tryptanthrin-induced down-regulation of IL-4 production, the expression of Th2-specific transcription factors, c-Maf and GATA-3, was analyzed by RT-PCR. The effects of Tryptanthrin on Th cell differentiation were evaluated using CD4(+) T cells purified from spleen cells of Sugi basic protein (SBP)-immunized BALB/c mice. In primary cultures, cells were stimulated with SBP and antigen-presenting cells under neutral or Th2-skewing conditions in the presence or absence of Tryptanthrin. Cytokines produced by differentiated Th cells in secondary cultures were analyzed by ELISA. The effects of Tryptanthrin on IgE-mediated degranulation and IL-4 production were determined using rat basophilic leukemia (RBL-2H3) cells. Phosphorylation of ERK1/2 and Akt in Tryptanthrin-treated RBL-2H3 cells was analyzed to determine the mechanism of Tryptanthrin actions.
Tryptanthrin suppressed c-Maf mRNA expression in Th2 clone cells, and even under Th2-skewing conditions, Tryptanthrin inhibited differentiation toward the Th2 phenotype, which is an essential event for the initiation phase of allergic diseases. Tryptanthrin also inhibited the IgE-mediated degranulation of and IL-4 production by RBL-2H3 cells, probably due to inhibiting IgE-mediated signaling pathways, including the phosphorylation of ERK1/2 and Akt.
These findings suggest that Tryptanthrin effectively inhibits the effector and exacerbation responses, as well as the initiator responses, of Type I allergy. Thus, Tryptanthrin may have beneficial effects for immediate-type allergic responses.
色酮是从蓼科植物中分离出来的一种化合物，是一种具有多种生物活性的民间药物。
过敏疾病是由过敏原特异性辅助性 T 细胞 2（Th2）细胞的发展引发的，并在效应阶段由嗜碱性粒细胞和肥大细胞脱颗粒和细胞因子释放而放大。我们发现色酮可以下调 Th2 细胞产生的 IL-4，而 Th1 细胞产生的 IFN-γ不受影响。由于嗜碱性粒细胞和效应 Th2 细胞产生的 IL-4 已被证明在 Th2 主导的过敏反应的发展和放大中发挥重要作用，因此我们研究了色酮对体外 I 型过敏的起始和效应阶段反应的影响。
为了确定色酮诱导的 IL-4 产生下调的机制，通过 RT-PCR 分析 Th2 特异性转录因子 c-Maf 和 GATA-3 的表达。使用从 Sugi 基础蛋白（SBP）免疫的 BALB/c 小鼠脾细胞中纯化的 CD4+T 细胞评估色酮对 Th 细胞分化的影响。在原发性培养物中，在存在或不存在色酮的情况下，用 SBP 和抗原呈递细胞在中性或 Th2 偏倚条件下刺激分化的 Th 细胞。通过 ELISA 分析次级培养物中分化的 Th 细胞产生的细胞因子。使用大鼠嗜碱性白血病（RBL-2H3）细胞测定色酮对 IgE 介导的脱颗粒和 IL-4 产生的影响。通过分析色酮处理的 RBL-2H3 细胞中 ERK1/2 和 Akt 的磷酸化来确定色酮作用的机制。
色酮抑制 Th2 克隆细胞中 c-Maf mRNA 的表达，甚至在 Th2 偏倚条件下，色酮也抑制向 Th2 表型的分化，这是过敏疾病起始阶段的必要事件。色酮还抑制 RBL-2H3 细胞的 IgE 介导的脱颗粒和 IL-4 产生，可能是由于抑制 IgE 介导的信号通路，包括 ERK1/2 和 Akt 的磷酸化。
这些发现表明，色酮有效地抑制 I 型过敏的效应和恶化反应以及起始反应。因此，色酮可能对即刻型过敏反应有益。
