State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
Biomed Pharmacother. 2017 Oct;94:758-766. doi: 10.1016/j.biopha.2017.07.118. Epub 2017 Aug 9.
Shufengjiedu Capsule (SFJD) is a type of Chinese traditional medicine compound for the treatment of acute upper respiratory tract infection. The present work aims to decipher the mechanism of SFJD.
In this study, we used target prediction and RNA sequence (RNA-Seq) based on transcriptome analysis to clarify the inflammation-eliminating mechanism of SFJD. Firstly, Pseudomonas aeruginosa (PAK) was used to induce acute lung injury in KM mice. After being treated by SFJD, the differently expressed genes were analyzed by RNA-Seq. Secondly, the chemical constituents of SFJD were identified by ultra-performance liquid chromatography quadrupole/time of flight mass spectrometry (UPLC/Q-TOF-MS) and submitted to PharmMapper to predict targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and String 9.1 websites were employed to establish the interaction network of inflammation of these targets.
The results indicated that SFJD alleviated PAK induced lung injury in KM mice. We infer that the mechanism is a complex network containing 15 pathways related to inflammation regulated by 16 types of components from six types of herbs via 29 proteins. The ERK signaling pathway was a key pathway among them, which was predicted to be regulated by 14 types of components in SFJD. Phillyrin, emodin, and verbenalin were screened out by binding capacity, and the synergistic effect of them was further confirmed.
Various components of SFJD ameliorated PAK induced upper respiratory tract infection via multiple targets, of which ERK phosphorylation might be the key event regulated specifically by verbenalin, phillyrin and emodin.
疏风解毒胶囊（SFJD）是一种治疗急性上呼吸道感染的中药复方。本研究旨在解析 SFJD 的作用机制。
本研究采用基于转录组分析的靶标预测和 RNA 测序（RNA-Seq）方法，阐明 SFJD 的抗炎机制。首先，采用铜绿假单胞菌（PAK）诱导 KM 小鼠急性肺损伤模型，SFJD 治疗后，采用 RNA-Seq 分析差异表达基因。其次，采用超高效液相色谱-四极杆飞行时间质谱联用（UPLC/Q-TOF-MS）技术鉴定 SFJD 的化学成分，并通过 PharmMapper 预测靶标。采用京都基因与基因组百科全书（KEGG）和 String 9.1 网站构建这些靶标炎症相关的相互作用网络。
结果表明，SFJD 减轻了 PAK 诱导的 KM 小鼠肺损伤。我们推断其作用机制是一个复杂的网络，包含 16 种成分通过 29 种蛋白调节 15 条与炎症相关的通路，这 16 种成分来源于 6 种草药。其中 ERK 信号通路是一个关键通路，SFJD 中推测有 14 种成分可以调节该通路。通过结合能力筛选出汉黄芩素、大黄素和马鞭草苷，并进一步证实了它们的协同作用。
SFJD 的多种成分通过多个靶标改善了 PAK 诱导的上呼吸道感染，其中 ERK 磷酸化可能是被马鞭草苷、汉黄芩素和大黄素特异性调节的关键事件。
