Yang Jing, Shen Xin, Qin Mi, Zhou Ping, Huang Fei-Hong, You Yun, Wang Long, Wu Jian-Ming
Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, PR China.
School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China.
Heliyon. 2024 Jan 18;10(3):e24336. doi: 10.1016/j.heliyon.2024.e24336. eCollection 2024 Feb 15.
Qing-Jin-Hua-Tan decoction (QJHTD) is a classic traditional Chinese medicine (TCM) prescription that first appeared in the ancient book Yi-Xue-Tong-Zhi. QJHTD has shown effectiveness for treating chronic obstructive pulmonary disease (COPD), although its mechanisms of action are still perplexing. The molecular mechanisms underlying the curative effects of QJHTD on COPD is worth exploring.
antiapoptotic and antiinflammatory activities of QJHTD were evaluated using cell viability, proliferation, apoptosis rate, and expression of IL-1β and TNF-α in BEAS-2B and RAW264.7 cells challenged with cigarette smoke (CS) extract (CSE) and lipopolysaccharide (LPS). therapeutic activities of QJHTD were evaluated using respiratory parameters (peak inspiratory flow (PIFb) and peak expiratory flow (PEFb) values), histopathology (mean linear intercept, MLI), and proinflammatory cytokine (IL-1β and TNF-α) and cleaved caspase-3 (c-Casp3) levels in the lung tissue of CS-LPS-exposed BALB/c mice. Network pharmacology-based prediction, transcriptomic analysis, and metabolic profiling were employed to investigate the signaling molecules and metabolites pertinent to the -COPD action of QJHTD.
Increased cell viability and proliferation with decreased apoptosis rate and proinflammatory cytokine expression were noted after QJHTD intervention. QJHTD administration elevated PEFb and PIFb values, reduced MLI, and inhibited IL-1β, TNF-α, and c-Casp3 expression . Integrated network pharmacology-transcriptomics revealed that suppressing inflammatory signals (IL-1β, IL-6, TNF, IκB-NF-κB, TLR, and MAPK) and apoptosis contributed to the -COPD property of QJHTD. Metabolomic profiling unveiled prominent roles for the suppression of apoptosis and sphingolipid (SL) metabolism and the promotion of choline (Ch) metabolism in the -COPD effect of QJHTD. Integrative transcriptomics-metabolomics unraveled the correlation between SL metabolism and apoptosis. molecular docking revealed that acacetin, as an active compound in QJHTD, could bind with high affinity to MEK1, MEK2, ERK1, ERK2, Bcl2, NF-κB, and alCDase target proteins.
The therapeutic effect of QJHTD on COPD is dependent on regulating inflammatory signals and apoptosis-directed SL metabolism. These findings provide deeper insights into the molecular mechanism of action of QJHTD against COPD and justify its theoretical promise in novel pharmacotherapy for this multifactorial disease.
清金化痰汤（QJHTD）是一首经典的中药方剂，最早见于古籍《医学统旨》。清金化痰汤已显示出对慢性阻塞性肺疾病（COPD）的治疗效果，但其作用机制仍不明确。清金化痰汤治疗COPD的分子机制值得探索。
使用细胞活力、增殖、凋亡率以及在香烟烟雾（CS）提取物（CSE）和脂多糖（LPS）刺激的BEAS-2B和RAW264.7细胞中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达，评估清金化痰汤的抗凋亡和抗炎活性。使用呼吸参数（吸气峰流速（PIFb）和呼气峰流速（PEFb）值）、组织病理学（平均线性截距，MLI）以及在暴露于CS-LPS的BALB/c小鼠肺组织中的促炎细胞因子（IL-1β和TNF-α）和裂解的半胱天冬酶-3（c-Casp3）水平，评估清金化痰汤的治疗活性。采用基于网络药理学的预测、转录组分析和代谢谱分析，研究与清金化痰汤治疗COPD作用相关的信号分子和代谢物。
清金化痰汤干预后，细胞活力和增殖增加，凋亡率和促炎细胞因子表达降低。给予清金化痰汤可提高PEFb和PIFb值，降低MLI，并抑制IL-1β、TNF-α和c-Casp3的表达。综合网络药理学-转录组学研究表明，抑制炎症信号（IL-1β、IL-6、TNF、IκB-NF-κB、TLR和MAPK）和凋亡有助于清金化痰汤的抗COPD特性。代谢组学分析揭示了抑制凋亡和鞘脂（SL）代谢以及促进胆碱（Ch）代谢在清金化痰汤抗COPD作用中的重要作用。综合转录组学-代谢组学揭示了SL代谢与凋亡之间的相关性。分子对接显示，刺槐素作为清金化痰汤中的一种活性化合物，可与MEK1、MEK2、ERK1、ERK2、Bcl2、NF-κB和半胱天冬酶靶蛋白高亲和力结合。
清金化痰汤对COPD的治疗作用依赖于调节炎症信号和凋亡导向的SL代谢。这些发现为清金化痰汤治疗COPD的分子作用机制提供了更深入的见解，并证明了其在这种多因素疾病新药物治疗中的理论前景。
