Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, PR China.
J Ethnopharmacol. 2011 May 17;135(2):522-9. doi: 10.1016/j.jep.2011.03.060. Epub 2011 Apr 2.
ETHNOPHARMAOCOLOGICAL RELEVANCE: Shuang-Huang-Lian (SHL) is a traditional Chinese formula and has been used for the treatment of respiratory tract infections by inhalation. However, the pulmonary toxicity via inhalation is largely uninvestigated.
To evaluate the pulmonary toxicity of SHL following in vivo intratracheal spray to rats and in vitro exposures to A549 and Calu-3 cells.
Calu-3 and A549 cells were exposed to SHL, chlorogenic acid, baicalin and forsythin solutions and in vitro cytotoxicity was evaluated using an MTT assay, whilst rats were subjected to intratracheal administration of SHL solutions and in vivo toxicity was indicated by assaying the LDH activity and total protein content in bronchoalveolar lavage fluid (BALF) and observing the histopathologic changes of the lungs. Secretion of inflammatory mediators, including IL-6, IL-8 and TNF-α, in cell culture media and BALF was quantified by ELISA.
The MTT cell viability data revealed the presence of minor toxicity to Calu-3 or A549 cells following exposure to SHL and its major ingredients for 24h or 48 h. However, the cell cultural media showed no sign of inflammatory responses. The in vivo results showed that exposures to SHL at doses of up to 50mg/kg did not significantly increase the total protein content, the LDH activity and the concentrations of IL-6, IL-8 and TNF-α in BALF. However, although intratracheal sprayed SHL at doses of up to 6 mg/kg for histopathologic study and up to 25mg/kg for cell counts showed no sign of adverse effects, inhaled SHL at elevated doses appeared to induce alveolar fusion in the lung and significant increases in the cell number of monocytes and granulocytes in the BALF.
The results demonstrated that the pulmonary safety of inhaled SHL was dependent on the administered dose. Inhalation therapy of SHL may be safely used when the inhaled dose was properly controlled.
评估双黄莲（SHL）经体内气管内喷雾给药和体外暴露于 A549 和 Calu-3 细胞后的肺部毒性。
将 Calu-3 和 A549 细胞暴露于 SHL、绿原酸、黄芩苷和连翘酯苷溶液中，通过 MTT 测定法评估体外细胞毒性，而大鼠则接受 SHL 溶液气管内给药，通过测定支气管肺泡灌洗液（BALF）中的 LDH 活性和总蛋白含量以及观察肺的组织病理学变化来指示体内毒性。通过 ELISA 定量测定细胞培养物上清液和 BALF 中炎症介质（包括 IL-6、IL-8 和 TNF-α）的分泌。
MTT 细胞活力数据显示，暴露于 SHL 及其主要成分 24 小时或 48 小时后，Calu-3 或 A549 细胞的毒性较小。然而，细胞培养液中没有炎症反应的迹象。体内结果表明，暴露于高达 50mg/kg 的 SHL 剂量不会显著增加 BALF 中的总蛋白含量、LDH 活性以及 IL-6、IL-8 和 TNF-α的浓度。然而，尽管气管内喷雾 SHL 的剂量高达 6mg/kg 用于组织病理学研究和高达 25mg/kg 用于细胞计数未显示出不良反应迹象，但吸入较高剂量的 SHL 似乎会导致肺泡融合，并显著增加 BALF 中单核细胞和粒细胞的细胞数。
结果表明，吸入 SHL 的肺部安全性取决于给予的剂量。当适当控制吸入剂量时，SHL 的吸入疗法可能是安全的。
