Department of Anesthesiology, Columbia University Medical Center, 650 West 168th Street, Black Building 7-713, New York, NY 10032, USA.
Am J Respir Cell Mol Biol. 2013 Feb;48(2):157-63. doi: 10.1165/rcmb.2012-0231OC. Epub 2012 Oct 11.
The prevalence of asthma has increased in recent years, and is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to short-acting and long-acting β-agonists and inhaled corticosteroids (ICS). As many as 40% of patients with asthma use herbal therapies to manage asthma symptoms, often without proven efficacy or known mechanisms of action. Therefore, investigations of both the therapeutic and possible detrimental effects of isolated components of herbal treatments on the airway are important. We hypothesized that ginger and its active components induce bronchodilation by modulating intracellular calcium (Ca(2+)) in airway smooth muscle (ASM). In isolated human ASM, ginger caused significant and rapid relaxation. Four purified constituents of ginger were subsequently tested for ASM relaxant properties in both guinea pig and human tracheas: [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted ASM (100-300 μM), whereas [10]-gingerol failed to induce relaxation. In human ASM cells, exposure to [6]-gingerol, [8]-gingerol, and [6]-shogaol, but not [10]-gingerol (100 μM), blunted subsequent Ca(2+) responses to bradykinin (10 μM) and S-(-)-Bay K 8644 (10 μM). In A/J mice, the nebulization of [8]-gingerol (100 μM), 15 minutes before methacholine challenge, significantly attenuated airway resistance, compared with vehicle. Taken together, these novel data show that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering Ca(2+) regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics, including β(2)-agonists, in airway diseases such as asthma.
近年来，哮喘的患病率有所增加，其特征为气道高反应性和炎症。许多患者报告说，他们使用替代疗法来自我治疗哮喘症状，作为短效和长效β-激动剂和吸入皮质类固醇（ICS）的辅助治疗。多达 40%的哮喘患者使用草药疗法来控制哮喘症状，而这些疗法往往没有经过证实的疗效或已知的作用机制。因此，研究草药治疗的单个成分对气道的治疗和可能的有害影响非常重要。我们假设姜及其活性成分通过调节气道平滑肌（ASM）中的细胞内钙（Ca(2+)）来诱导支气管扩张。在分离的人 ASM 中，姜引起了显著而快速的松弛。随后，对姜的四种纯化成分在豚鼠和人气管中进行了 ASM 松弛特性的测试：[6]-gingerol、[8]-gingerol 和 [6]-shogaol 诱导预先收缩的 ASM 快速松弛（100-300 μM），而 [10]-gingerol 则不能诱导松弛。在人 ASM 细胞中，暴露于 [6]-gingerol、[8]-gingerol 和 [6]-shogaol，但不是 [10]-gingerol（100 μM），可使随后对缓激肽（10 μM）和 S-(-)-Bay K 8644（10 μM）的 Ca(2+)反应减弱。在 A/J 小鼠中，与载体相比，在乙酰甲胆碱挑战前 15 分钟雾化 [8]-gingerol（100 μM）可显著减轻气道阻力。总之，这些新数据表明，姜及其分离的活性成分 [6]-gingerol、[8]-gingerol 和 [6]-shogaol 可松弛 ASM，而 [8]-gingerol 可减轻气道高反应性，部分原因是通过改变 Ca(2+)(i)调节。这些纯化的化合物可能单独或与β(2)-激动剂等公认的治疗药物联合，为哮喘等气道疾病提供一种治疗选择。
