Department of Pulmonary and Critical Care Medicine, Tongde Hospital of Zhejiang Province, Hangzhou City, Zhejiang Province, People's Republic of China.
Department of Medical Oncology, Tongde Hospital of Zhejiang Province, Hangzhou City, Zhejiang Province, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2024 Aug 8;19:1819-1834. doi: 10.2147/COPD.S459814. eCollection 2024.
Sangbaipi decoction (SBPD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat acute exacerbation of chronic obstructive pulmonary disease (AECOPD), while the underlying pharmacological mechanism remains unclear due to the complexity of composition.
A TCM-active ingredient-drug target network of SBPD was constructed utilizing the TCM-Systems-Pharmacology database. AECOPD-relevant proteins were gathered from Gene Cards and the Online-Mendelian-Inheritance-in-Man database. Protein-protein interaction, GO and KEGG enrichment analyses of the targets from the intersection of SBPD and AECOPD targets were performed to identify the core signaling pathway, followed by molecular docking verification of its interaction with active ingredients. The network pharmacology results were checked using experiments. To induce AECOPD, rats were exposure to combined tobacco smoke and lipopolysaccharide (LPS). Then rats underwent gavage with stigmasterol (SM) after successful modeling. The involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling was investigated using its inhibitor, LY294002. Lung function and histopathology were examined. The levels of inflammatory cytokines in the lung and serum were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and/or Enzyme-linked immunosorbent assay (ELISA).
SM was recognized as an active ingredient of SBPD and stably bound to Akt1. SM improved lung function and histological abnormalities, concomitant with suppressed PI3K/Akt signaling, downregulated lung and serum Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) levels and serum transforming growth factor-β (TGF-β) levels and upregulated lung and serum Interleukin 10 (IL-10) levels in AECOPD rats. In AECOPD rats, LY294002 restored lung function, and it also improved lung histological abnormalities and inflammation, which was found to be potentiated by SM.
SM targets PI3K/Akt signaling to reduce lung injury and inflammation in AECOPD rats.
桑白皮汤（SBPD）是一种中药方剂，已广泛用于治疗慢性阻塞性肺疾病急性加重（AECOPD），但其作用机制尚不清楚，因为其成分复杂。
利用中药系统药理学数据库构建了 SBPD 的中药活性成分-药物靶标网络。从基因卡片和在线孟德尔遗传在线人类数据库中收集 AECOPD 相关蛋白。对 SBPD 和 AECOPD 靶标交集的靶标进行蛋白质-蛋白质相互作用、GO 和 KEGG 富集分析，以确定核心信号通路，然后对其与活性成分的相互作用进行分子对接验证。使用实验检查网络药理学结果。通过暴露于香烟烟雾和脂多糖（LPS）来诱导 AECOPD，然后在成功建模后用豆甾醇（SM）对大鼠进行灌胃。使用其抑制剂 LY294002 研究磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）信号通路的参与情况。通过定量逆转录-聚合酶链反应（qRT-PCR）、Western blot 和/或酶联免疫吸附测定（ELISA）检测肺和血清中炎症细胞因子的水平。
SM 被认为是 SBPD 的一种活性成分，并且与 Akt1 稳定结合。SM 改善了 AECOPD 大鼠的肺功能和组织学异常，同时抑制了 PI3K/Akt 信号通路，下调了肺和血清中白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）水平以及血清转化生长因子-β（TGF-β）水平，并上调了肺和血清中白细胞介素 10（IL-10）水平。在 AECOPD 大鼠中，LY294002 恢复了肺功能，并且还改善了肺组织学异常和炎症，发现 SM 可增强其作用。
SM 通过靶向 PI3K/Akt 信号通路来减轻 AECOPD 大鼠的肺损伤和炎症。
