Nagai Takayuki, Arai Yumiko, Emori Michiko, Nunome Shin-Yu, Yabe Takeshi, Takeda Tadahiro, Yamada Haruki
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku Tokyo 108-8641, Japan.
Int Immunopharmacol. 2004 Oct;4(10-11):1353-65. doi: 10.1016/j.intimp.2004.05.021.
Effects of a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST, Xiao-Qing-Long-Tang in Chinese)", which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g/kg/day from day 1 to 6 days after OVA inhalation, SST reduced the OVA-specific IgE antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. CD4(+) T cells obtained from the mouse lung produced more interleukin (IL)-4 and IL-5 but less interferon (IFN)-gamma than T cells from nonsensitized control animals. However, oral administration of SST reduced the production of IL-4 and IL-5 and the production of IFN-gamma returned to the control level. In addition, the IL-4 level was increased in the BAL fluid of the OVA-sensitized animals compared to the nonsensitized control, while the IFN-gamma levels decreased. SST reduced the IL-4 levels in the BAL fluids and returned the IFN-gamma level to control levels. Nerve growth factor (NGF) was increased in the BAL fluids of the OVA-sensitized mice over that of nonsensitized mice, but oral administration of SST augmented the NGF levels to approximately 2 times higher than in the sensitized mice. Although lung cells obtained from sensitized mice produced higher levels of NGF than nonsensitized mice, oral administration of SST augmented the production of NGF by the lung cells even higher ( approximately 2 times more than cells from sensitized mice). Administration of anti-NGF antibody to the airway blocked the effects of SST. These results suggest that SST modulates Th1/Th2 balance in the lungs and augmentation of NGF in the lungs may be related to the effects of SST. Pinellic acid (9S, 12S, 13S-trihydroxy-10E-octadecenoic acid), one component of the herbs of SST [Int. Immunopharmacol. 2 (2002) 1183], was purified from the tuber of Pinellia ternata Breitenbach. Oral administration of pinellic acid (50 microg/kg/day) also reduced the OVA-specific IgE antibody titer in BAL fluids from the sensitized mouse. This result suggests that pinellic acid is one of active ingredient(s) in SST.
在小鼠卵清蛋白(OVA)致敏的过敏性气道炎症模型(即支气管哮喘)中,研究了临床上用于治疗过敏性支气管哮喘的汉方(日本草药)“小青龙汤(SST,中文为小青龙汤)”的效果。在吸入OVA后的第1天至第6天,以0.5 g/kg/天的剂量口服SST,在吸入OVA后7天,SST降低了支气管肺泡灌洗(BAL)液中OVA特异性IgE抗体滴度。与未致敏对照动物的T细胞相比,从小鼠肺中获得的CD4(+) T细胞产生更多的白细胞介素(IL)-4和IL-5,但产生的干扰素(IFN)-γ较少。然而,口服SST减少了IL-4和IL-5的产生,并且IFN-γ的产生恢复到对照水平。此外,与未致敏对照相比,OVA致敏动物的BAL液中IL-4水平升高,而IFN-γ水平降低。SST降低了BAL液中的IL-4水平,并使IFN-γ水平恢复到对照水平。OVA致敏小鼠的BAL液中神经生长因子(NGF)比未致敏小鼠的升高,但口服SST使NGF水平增加到比致敏小鼠高约2倍。虽然从致敏小鼠获得的肺细胞产生的NGF水平高于未致敏小鼠,但口服SST使肺细胞产生的NGF更高(比致敏小鼠的细胞多约2倍)。向气道注射抗NGF抗体可阻断SST的作用。这些结果表明,SST调节肺中的Th1/Th2平衡,肺中NGF的增加可能与SST的作用有关。从半夏(Pinellia ternata Breitenbach)块茎中纯化出小青龙汤草药成分之一的半夏酸(9S,12S,13S-三羟基-10E-十八碳烯酸)。口服半夏酸(50μg/kg/天)也降低了致敏小鼠BAL液中OVA特异性IgE抗体滴度。该结果表明半夏酸是小青龙汤中的活性成分之一。