Department of Internal Medicine, Taipei Medical University Hospital, Taiwan.
Evid Based Complement Alternat Med. 2011;2011:132374. doi: 10.1093/ecam/nep088. Epub 2011 Feb 10.
S-Petasin is the main sesquiterpene of Petasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1-5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma. S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC(50)) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis, S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (K(i)) of 25.3 and 18.1 μM, respectively. Both IC(50) and K(i) values for PDE3 were significantly greater than those for PDE4. S-Petasin (10-30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition, S-petasin (10-30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG(2a) level in serum of these mice. The PDE4(H) value of S-petasin was >300 μM; therefore, its PDE4(H)/PDE4(L) value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.
S-金合欢素是台湾传统民间药物大泽兰中的一种主要倍半萜烯，用于治疗高血压、肿瘤和哮喘。本研究旨在探讨 S-金合欢素对磷酸二酯酶（PDE）1-5 的抑制作用，并在卵清蛋白（OVA）诱导的变应性哮喘小鼠模型中观察其对气道高反应性（AHR）的抑制作用。S-金合欢素呈浓度依赖性抑制 PDE3 和 PDE4 活性，半数抑制浓度（IC50）分别为 25.5 和 17.5 μM。根据 Lineweaver-Burk 分析，S-金合欢素竞争性抑制 PDE3 和 PDE4 活性，抑制剂结合的解离常数（K(i)）分别为 25.3 和 18.1 μM。PDE3 的 IC50 和 K(i)值均显著大于 PDE4。S-金合欢素（10-30 μmol/kg，皮下注射）剂量依赖性显著降低致敏和激发后小鼠由乙酰甲胆碱（MCh）引起的增强呼气暂停（P(enh)）值。它还显著抑制了总炎性细胞、淋巴细胞、中性粒细胞、嗜酸性粒细胞和细胞因子（白细胞介素（IL）-2、IL-4 和 IL-5、肿瘤坏死因子（TNF）-α 和干扰素（IFN）-γ）在这些小鼠的支气管肺泡灌洗液（BALF）中的水平升高。此外，S-金合欢素（10-30 μmol/kg，皮下注射）剂量依赖性显著降低了这些小鼠血清和 BALF 中的总和 OVA 特异性免疫球蛋白 E（IgE）水平，并增强了血清中的 IgG(2a)水平。S-金合欢素的 PDE4(H)值大于 300 μM；因此，其 PDE4(H)/PDE4(L)值计算大于 17。综上所述，本研究结果至少部分解释了为什么大泽兰被用作台湾治疗哮喘的民间药物。
