School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
BMC Complement Altern Med. 2014 Oct 15;14:402. doi: 10.1186/1472-6882-14-402.
The fruit hull of Gleditsia sinensis (FGS) used in traditional Asian medicine was reported to have a preventive effect on lung inflammation in an acute lung injury (ALI) mouse model. Here, we explored FGS as a possible therapeutics against inflammatory lung diseases including ALI, and examined an underlying mechanism for the effect of FGS.
The decoction of FGS in water was prepared and fingerprinted. Mice received an intra-tracheal (i.t.) FGS 2 h after an intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). The effect of FGS on lung inflammation was determined by chest imaging of NF-κB reporter mice, counting inflammatory cells in bronchoalveolar lavage fluid, analyzing lung histology, and performing semi-quantitative RT-PCR analysis of lung tissue. Impact of Nrf2 on FGS effect was assessed by comparing Nrf2 knockout (KO) and wild type (WT) mice that were treated similarly.
Bioluminescence from the chest of the reporter mice was progressively increased to a peak at 16 h after an i.p. LPS treatment. FGS treatment 2 h after LPS reduced the bioluminescence and the expression of pro-inflammatory cytokine genes in the lung. While suppressing the infiltration of inflammatory cells to the lungs of WT mice, FGS post-treatment failed to reduce lung inflammation in Nrf2 KO mice. FGS activated Nrf2 and induced Nrf2-dependent gene expression in mouse lung.
FGS post-treatment suppressed lung inflammation in an LPS-induced ALI mouse model, which was mediated at least in part by Nrf2. Our results suggest a therapeutic potential of FGS on inflammatory lung diseases.
传统亚洲医学中使用的皂荚果(FGS)的果皮据称对急性肺损伤(ALI)小鼠模型中的肺部炎症具有预防作用。在这里,我们探讨了 FGS 作为一种治疗包括 ALI 在内的炎症性肺病的潜在疗法,并研究了 FGS 作用的潜在机制。
用水制备 FGS 的煎剂并进行指纹图谱分析。在腹腔内(i.p.)注射脂多糖(LPS)后 2 小时,给小鼠进行气管内(i.t.)FGS 处理。通过 NF-κB 报告小鼠的胸部成像、支气管肺泡灌洗液中炎症细胞的计数、肺组织学分析以及半定量 RT-PCR 分析来确定 FGS 对肺炎症的影响。通过比较接受类似处理的 Nrf2 敲除(KO)和野生型(WT)小鼠,评估 Nrf2 对 FGS 作用的影响。
来自报告小鼠胸部的生物发光在 LPS 腹腔注射后 16 小时逐渐增加至峰值。在 LPS 处理后 2 小时给予 FGS 治疗可降低生物发光和肺部促炎细胞因子基因的表达。虽然 FGS 后处理抑制了 WT 小鼠肺部炎症细胞的浸润,但在 Nrf2 KO 小鼠中未能减轻肺炎症。FGS 激活了 Nrf2,并诱导了小鼠肺部 Nrf2 依赖性基因表达。
FGS 后处理抑制了 LPS 诱导的 ALI 小鼠模型中的肺炎症,这至少部分是由 Nrf2 介导的。我们的结果表明 FGS 对炎症性肺病具有治疗潜力。