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疏风解毒胶囊通过马鞭草苷激活GPR18减轻脂多糖诱导的急性肺炎症损伤。

Shufeng Jiedu Capsules Alleviate Lipopolysaccharide-Induced Acute Lung Inflammatory Injury via Activation of GPR18 by Verbenalin.

作者信息

Yuan Ying, Liao Qingwu, Xue Mingming, Shi Yujing, Rong Ling, Song Zhenju, Tong Zhaoyang, Zheng Wuhong, Zhu Qiang, Cui Xiaolan, Tao Zhengang

机构信息

Department of Presbyatrics, Affiliated Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Anesthesiology, Affiliated Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Cell Physiol Biochem. 2018;50(2):629-639. doi: 10.1159/000494184. Epub 2018 Oct 11.

Abstract

BACKGROUND/AIMS: Acute respiratory tract infection (ARTI) is the most common reason for outpatient physician office visits. Although powerful and significant in the treatment of infections, antibiotics used for ARTI inappropriately have been an important contributor to antibiotic resistance. We previously reported that Shufeng Jiedu Capsule (SJC) can effectively amplify anti-inflammatory signaling during infection. In this study, we aimed to systematically explore its composition and the mechanism of its effects in ARTI.

METHODS

Pseudomonas aeruginosa (PAK) strain was used to generate a mouse model of ARTI, which were then treated with different drugs or compounds to determine the corresponding anti-inflammatory roles. High-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry. was conducted to detect the chemical compounds in SJC. RNAs from the lung tissues of mice were prepared for microarray analysis to reveal globally altered genes and the pathways involved after SJC treatment.

RESULTS

SJC significantly inhibited the expression and secretion of inflammatory factors from PAK-induced mouse lung tissues or lipopolysaccharide-induced peritoneal macrophages. Verbenalin, one of the bioactive compounds identified in SJC, also showed notable anti-inflammatory effects. Microarray data revealed numerous differentially expressed genes among the different treatment groups; here, we focused on studying the role of GPR18. We found that the anti-inflammatory role of verbenalin was attenuated in GPR18 knockout mice compared with wild-type mice, although no statistically significant difference was observed in the untreated PAK-induced mice types.

CONCLUSION

Our data not only showed the chemical composition of SJC, but also demonstrated that verbenalin was a significant anti-inflammatory compound, which may function through GPR18.

摘要

背景/目的:急性呼吸道感染(ARTI)是门诊就医的最常见原因。尽管抗生素在感染治疗中作用强大且显著,但不恰当地用于ARTI已成为抗生素耐药性的一个重要因素。我们之前报道过,疏风解毒胶囊(SJC)在感染期间可有效增强抗炎信号。在本研究中,我们旨在系统探究其成分及其在ARTI中的作用机制。

方法

使用铜绿假单胞菌(PAK)菌株建立ARTI小鼠模型,然后用不同药物或化合物进行治疗,以确定相应的抗炎作用。采用高效液相色谱 - 四极杆飞行时间串联质谱法检测SJC中的化学成分。制备小鼠肺组织的RNA用于微阵列分析,以揭示SJC治疗后整体改变的基因及相关通路。

结果

SJC显著抑制PAK诱导的小鼠肺组织或脂多糖诱导的腹腔巨噬细胞中炎症因子的表达和分泌。马鞭草苷是在SJC中鉴定出的生物活性化合物之一,也显示出显著的抗炎作用。微阵列数据揭示了不同治疗组之间众多差异表达的基因;在此,我们重点研究GPR18的作用。我们发现,与野生型小鼠相比,马鞭草苷在GPR18基因敲除小鼠中的抗炎作用减弱,尽管在未治疗的PAK诱导小鼠类型中未观察到统计学上的显著差异。

结论

我们的数据不仅显示了SJC的化学成分,还证明了马鞭草苷是一种重要的抗炎化合物,其可能通过GPR18发挥作用。

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