College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China.
Department of Respiration, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China.
Biomed Res Int. 2022 Feb 7;2022:8752325. doi: 10.1155/2022/8752325. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and poor prognosis. The prognostic signatures related to conventional therapy response remain limited. The Wenfei Buqi Tongluo (WBT) formula, a traditional Chinese medicine (TCM) formula, has been widely utilized to treat respiratory diseases in China, which is particularly effective in promoting inflammatory absorption. In this study, we aim to explore the mechanism of the WBT formula in the inhibition of inflammatory response during IPF, based on network pharmacology and experiments.
Network pharmacology was applied to predict the changes of biological processes and potential pathways for the WBT formula against IPF. Histopathological changes, inflammatory factors (IL-6, IL-1, and TNF-), and the proteins of the TLR4/MyD88/NF-B pathway in bleomycin- (BLM-) induced mice model were examined by hematoxylin-eosin (H&E), Masson or immunohistochemistry staining, Western blot, and enzyme-linked immunosorbent assay analysis.
A total of 163 possible components and 167 potential targets between the WBT formula and IPF were obtained. The enrichments of network pharmacology showed that inflammation response, TNF, and NF-B pathways were involved in the treatment of WBT against IPF. The experiments indicated that the WBT formula could ameliorate inflammatory exudation and collagen deposition at a histopathology level in the BLM-induced mice model. The levels of IL-6, IL-1, and TNF- were reduced after the WBT formula treatment. Moreover, the expressions of phosphorylated-NF-B p65, TLR4, and MyD88 were significantly downregulated by the WBT formula, compared with the BLM-induced group.
These results indicated that the WBT formula can suppress BLM-induced IPF in a mouse model by inhibiting the inflammation via the TLR4/MyD88/NF-B pathway. This study provides a new insight into the molecular mechanisms of the WBT formula in the application at the clinic.
特发性肺纤维化（IPF）是一种死亡率高、预后差的进行性疾病。与常规治疗反应相关的预后标志物仍然有限。温肺补气通络方（WBT）是一种中药（TCM）配方，在中国被广泛用于治疗呼吸系统疾病，尤其在促进炎症吸收方面效果显著。在这项研究中，我们旨在基于网络药理学和实验探索 WBT 配方抑制 IPF 中炎症反应的机制。
网络药理学用于预测 WBT 配方对 IPF 的生物过程和潜在途径的变化。通过苏木精-伊红（H&E）、Masson 或免疫组织化学染色、Western blot 和酶联免疫吸附试验分析，观察博来霉素（BLM）诱导的小鼠模型中的组织病理学变化、炎症因子（IL-6、IL-1 和 TNF-）和 TLR4/MyD88/NF-B 通路的蛋白。
共获得 WBT 配方与 IPF 之间的 163 种可能成分和 167 个潜在靶点。网络药理学的富集结果表明，炎症反应、TNF 和 NF-B 途径参与了 WBT 治疗 IPF。实验表明，WBT 配方可改善 BLM 诱导的小鼠模型中的炎症渗出和胶原沉积。WBT 配方治疗后，IL-6、IL-1 和 TNF-水平降低。此外，与 BLM 诱导组相比，WBT 配方显著下调了磷酸化-NF-B p65、TLR4 和 MyD88 的表达。
这些结果表明，WBT 配方可通过抑制 TLR4/MyD88/NF-B 通路抑制 BLM 诱导的 IPF，为 WBT 配方在临床上的应用提供了新的分子机制见解。
