School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, Shaanxi Province, 710061, People's Republic of China.
Inflammation. 2017 Aug;40(4):1111-1122. doi: 10.1007/s10753-017-0553-1.
Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.
急性肺损伤 (ALI) 的特征是肺部广泛炎症和肺泡毛细血管破坏，导致高发病率和死亡率。从延胡索中分离出的紫堇灵在以前的研究中显示出具有强大的抗炎作用。本研究旨在评估紫堇灵对脂多糖 (LPS) 诱导的 ALI 的保护作用，并阐明其体内和体外的潜在机制。在 LPS（30mg/kg）鼻内给药诱导 ALI 之前，通过腹腔注射给予小鼠紫堇灵（1、3 或 10mg/kg），分别在 1 小时和 12 小时进行给药。在 LPS 挑战后采集血样、肺组织和支气管肺泡灌洗液 (BALF)。此外，我们使用 LPS 诱导的肺上皮细胞 A549 来研究紫堇灵对肺损伤的作用机制。结果表明，紫堇灵预处理可显著降低肺湿重/干重（W/D）比值，降低 LPS 刺激小鼠 BALF 和血清中促炎细胞因子 TNF-α 和 IL-6 的水平，并减轻肺组织病理学变化。此外，Western blot 结果表明，紫堇灵抑制了 LPS 诱导的核因子-κB（NF-κB）p65 和 IκBα的磷酸化。总之，我们的结果表明，紫堇灵通过抑制促炎细胞因子 TNF-α和 IL-6 的产生和 NF-κB 信号通路的激活，对 LPS 诱导的小鼠急性肺损伤起保护作用。综上所述，紫堇灵可能对预防和治疗肺部炎症性疾病（如 ALI）有用。
