Knipping Karen, van Esch Elisabeth C A M, Wijering Selva C, van der Heide Sicco, Dubois Anthony E, Garssen Johan
University of Utrecht, Department of Pharmaceutical Sciences, Sorbonnelaan 16, 3508 TC Utrecht, The Netherlands.
Exp Biol Med (Maywood). 2008 Nov;233(11):1469-77. doi: 10.3181/0803-RM-97. Epub 2008 Aug 14.
The discovery of drugs that can be used for the treatment of allergic disease is important in human health. Arctium lappa Linne (Compositae) (AL) has been used as a traditional medicine in Brazil and throughout Asia and is known to have an anti-inflammatory effect. In this study, the inhibitory effects of AL on degranulation and the release of mediators as well as on inhibition of cys-leukotriene biosynthesis by basophils were investigated. AL was selected out of 10,000 herbal extracts in a set-up for high throughput screening in which the degree of degranulation was monitored by the release of beta-hexosaminidase from rat basophil leukemia (RBL-2H3) cells. The AL extract significantly reduced degranulation and biosynthesis of cys-leukotrienes of human basophils in peripheral blood mono-nuclear cells (PBMCs) (50% inhibitory concentration [IC(50)] = 8.3 and 11.4 microg/ml, respectively). Viability and metabolic activity of the PBMCs were not affected. Although arctiin, the active component of AL that has been described in the literature, was not able to reduce degranulation in RBL-2H3 cells, a single high-performance liquid chromatography (HPLC) fraction from the AL extract inhibited beta-hexosaminidase release (IC(50) = 22.2 microg/ml). Topical administration of an aqueous extract of AL (5 mg/ear) on the ear of whey-sensitized mice 4 hrs before challenge with whey in the ear inhibited acute ear swelling by 50% in an in vivo cow's milk allergic model. The extract had no effect in this model when administered orally. In conclusion, the active component present in the active HPLC fraction of the AL extract was able to significantly reduce the release of inflammatory mediators through inhibition of degranulation and cys-leukotriene release in vitro. In addition, this active component was able to inhibit acute skin response in mice in vivo, indicating that AL is a very promising natural component for use in anti-allergic treatment.
发现可用于治疗过敏性疾病的药物对人类健康至关重要。牛蒡（菊科）在巴西和整个亚洲都被用作传统药物，已知具有抗炎作用。在本研究中，研究了牛蒡对嗜碱性粒细胞脱颗粒、介质释放以及对其抑制半胱氨酰白三烯生物合成的作用。在高通量筛选实验中，从10000种草药提取物中挑选出牛蒡，通过大鼠嗜碱性粒细胞白血病（RBL - 2H3）细胞释放β - 己糖胺酶来监测脱颗粒程度。牛蒡提取物显著降低了外周血单核细胞（PBMCs）中人类嗜碱性粒细胞的脱颗粒和半胱氨酰白三烯的生物合成（50%抑制浓度[IC(50)]分别为8.3和11.4微克/毫升）。PBMCs的活力和代谢活性未受影响。尽管文献中描述的牛蒡活性成分牛蒡苷不能降低RBL - 2H3细胞的脱颗粒，但牛蒡提取物的一个高效液相色谱（HPLC）单一馏分可抑制β - 己糖胺酶释放（IC(50)=22.2微克/毫升）。在体内牛奶过敏模型中，在用乳清攻击乳清致敏小鼠耳部前4小时，局部给予牛蒡水提取物（5毫克/耳）可使急性耳部肿胀抑制50%。口服该提取物在该模型中无效。总之，牛蒡提取物活性HPLC馏分中的活性成分能够通过在体外抑制脱颗粒和半胱氨酰白三烯释放来显著减少炎症介质的释放。此外，该活性成分能够在体内抑制小鼠的急性皮肤反应，表明牛蒡是一种非常有前景的用于抗过敏治疗的天然成分。
