Zhu Guosong, Zhang Jiaqiang, Yang Yali, Zhang Haoran, Jin Wenwen, Su Fangchu, Liang Junting, Wang Kaiwei, Zhang Jianhua, Chen Chuanliang
Department of Anesthesia and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Medical Engineering Technology and Data Mining Institute, Zhengzhou University, Zhengzhou, China.
Front Pharmacol. 2021 Apr 26;12:650780. doi: 10.3389/fphar.2021.650780. eCollection 2021.
georgi is one of the most widely studied TCMs; its effects in ALI have been studied in a large number of experiments, and the efficacy of volatile oil from TCM remains to be studied. The volatile component of georgi was selected to act on the key target of acute lung injury and was preliminarily studied for its specific molecular mechanism. The volatile active substances of georgi were extracted by GC-MS, and the active ingredients related with the occurrence and development of acute lung injury were searched and matched by the TCMSP database. The pharmacologic data and analysis platform of TCM were used to retrieve and screen for the volatile active components and the possible therapeutic targets of georgi. In addition, acute lung injury was searched in the disease target database to identify the corresponding disease target proteins, thereby establishing a protein-protein interaction network. Finally, the effects of wogonin on the apoptotic and inflammatory factors in the acute lung injury cell model were analyzed experimentally. We identified 100 candidate targets and successfully constructed a complex target network. The targets identified by the above gene enrichment analysis played important roles in the autoimmune disease cell cycle apoptosis and related signaling pathways. The KEGG pathway analysis showed that most of the target genes were involved in the inflammatory response regulation of the TRP, PI3K-Akt, and IL-17 signaling pathways. The participation of wogonin in the specific regulatory pathways of PI3K-Akt signaling and IL-17 signaling was verified through experiments. In the lung-injured cell model, the results showed that wogonin inhibited the apoptosis of injured lung cells by inhibiting the expression of gene and the activation of cleaved gene while increasing Bcl-2 expression. In addition, wogonin inhibited the expression of the abovementioned inflammatory factors and further inhibited the inflammatory response in the lung injury cells. The results of pharmacological network analysis can predict and explain the regulation mechanism of multi-target and multi-pathway of TCM components. This study identified the potential target and important pathway of wogonin in regulating acute lung injury. At the same time, the accuracy of network pharmacological prediction is also preliminarily verified by molecular biology experiment.
地锦草是研究最为广泛的传统中药之一；其在急性肺损伤中的作用已在大量实验中得到研究，而中药挥发油的功效仍有待研究。选取地锦草的挥发成分作用于急性肺损伤的关键靶点，并对其具体分子机制进行了初步研究。采用气相色谱 - 质谱联用（GC - MS）法提取地锦草的挥发性活性物质，并通过中药系统药理学数据库与分析平台（TCMSP数据库）检索匹配与急性肺损伤发生发展相关的活性成分。利用中药药理数据与分析平台检索筛选地锦草的挥发性活性成分及其可能的治疗靶点。此外，在疾病靶点数据库中搜索急性肺损伤，以鉴定相应的疾病靶点蛋白，从而建立蛋白质 - 蛋白质相互作用网络。最后，通过实验分析汉黄芩素对急性肺损伤细胞模型中凋亡和炎症因子的影响。我们鉴定出100个候选靶点，并成功构建了一个复杂的靶点网络。上述基因富集分析鉴定出的靶点在自身免疫性疾病细胞周期凋亡及相关信号通路中发挥重要作用。KEGG通路分析表明，大多数靶基因参与了瞬时受体电位通道（TRP）、磷脂酰肌醇 - 3激酶 - 蛋白激酶B（PI3K - Akt）和白细胞介素 - 17（IL - 17）信号通路的炎症反应调节。通过实验验证了汉黄芩素参与PI3K - Akt信号通路和IL - 17信号通路的特异性调节途径。在肺损伤细胞模型中，结果表明汉黄芩素通过抑制基因表达和裂解基因的激活，同时增加Bcl - 2表达，抑制受损肺细胞的凋亡。此外，汉黄芩素抑制上述炎症因子的表达，并进一步抑制肺损伤细胞中的炎症反应。药理网络分析结果可以预测和解释中药成分多靶点、多途径的调控机制。本研究确定了汉黄芩素在调节急性肺损伤中的潜在靶点和重要途径。同时，分子生物学实验也初步验证了网络药理学预测的准确性。
