Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2024-01-28 , DOI: 10.1016/j.jep.2024.117816 Hui Ren 1 , Wenxing Wu 1 , Jiangyan Chen 1 , Quan Li 2 , Hengbin Wang 2 , Dawei Qian 1 , Sheng Guo 1 , Jin-Ao Duan 1
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Ethnopharmacological relevance
Bufei Huoxue capsule (BHC) as a classic Chinese patent medicine formula, has the efficacy of tonifying the lungs and activating the blood. It has been extensively used in China for the treatment of chronic obstructive pulmonary disease (COPD) clinically. However, its mechanism is still unclear, which hampers the applications of BHC in treating COPD.
Aim of the study
The purpose of the present study was to demonstrate the protective efficacy and mechanism of BHC on COPD model rats by integrating serum metabolomics analysis and network pharmacology study.
Materials and methods
A COPD rat model was established by cigarette fumigation combined with lipopolysaccharide (LPS) airway drip for 90 consecutive days. After oral administration for 30 days, the rats were placed in the body tracing box of the EMKA Small Animal Noninvasive Lung Function Test System to determine lung function related indexes. Histopathological alteration was observed by H&E staining and Masson staining. The serum levels of inflammatory cytokine, matrix metalloprotein 9, and laminin were determined by ELISA kits. Oxidative stress levels were tested by biochemical methods. UHPLC-Q-TOF/MS analysis of serum metabolomics and network pharmacology were performed to reveal the bioactive metabolites, key components and pathways for BHC treating COPD. WB and ELISA kits were used to verify the effects of BHC on key pathway.
Results
BHC could improve lung function, immunity, lung histopathological changes and collagen deposition in COPD model rats. It also could significantly reduce inflammatory response in vivo, regulate oxidative stress level, reduce laminin content, and regulate protease-antiprotease balance. Metabolomics analysis found 46 biomarkers of COPD, of which BHC significantly improved the levels of 23 differential metabolites including arachidonic acid, leukotriene B4 and prostaglandin E2. Combined with the results of network pharmacology, the components of BHC, such as calycosin, oxypaeoniflora, (S)-bavachin and neobavaisoflavone could play therapeutic roles through the arachidonic acid pathway. In addition, the results of WB and ELISA indicated that BHC could suppress the expressions of COX2 and 5-LOX in lung tissues and inhibit the generation of AA and its metabolites in serum samples. Regulation of arachidonic acid metabolic pathway may be the crucial mechanism for BHC treating COPD.
Conclusions
In summary, the studies indicated that BHC exhibited the protective effect on COPD model rats by anti-inflammatory and anti-oxidative properties through arachidonic acid metabolism pathway. This study provided beneficial support for the applications of BHC in treating COPD.
中文翻译：
补肺活血胶囊对慢性阻塞性肺疾病大鼠活性代谢物的综合血清代谢组学和网络药理学分析及机制探讨
民族药理学相关性
补肺活血胶囊（BHC）作为经典中成药配方，具有补肺活血的功效。在我国临床上已广泛用于治疗慢性阻塞性肺疾病（COPD）。但其作用机制尚不清楚，这限制了BHC在治疗COPD中的应用。
研究目的
本研究的目的是通过整合血清代谢组学分析和网络药理学研究来论证BHC对COPD模型大鼠的保护功效和机制。
材料和方法
采用香烟熏蒸联合脂多糖（LPS）气道滴注连续90 d建立COPD大鼠模型。口服给药30天后，将大鼠置于EMKA小动物无创肺功能检测系统体迹盒中，测定肺功能相关指标。通过H&E染色和Masson染色观察组织病理学改变。采用ELISA试剂盒测定血清炎症细胞因子、基质金属蛋白9和层粘连蛋白的水平。通过生化方法测试氧化应激水平。对血清代谢组学和网络药理学进行 UHPLC-Q-TOF/MS 分析，揭示 BHC 治疗 COPD 的生物活性代谢物、关键成分和通路。采用WB和ELISA试剂盒验证BHC对关键通路的影响。
结果
BHC可改善COPD模型大鼠的肺功能、免疫力、肺组织病理学变化和胶原沉积。它还可以显着减轻体内炎症反应，调节氧化应激水平，降低层粘连蛋白含量，调节蛋白酶-抗蛋白酶平衡。代谢组学分析发现了 46 个 COPD 生物标志物，其中 BHC 显着提高了花生四烯酸、白三烯 B4 和前列腺素 E2 等 23 种差异代谢物的水平。结合网络药理学结果，BHC成分如毛蕊异黄酮、氧芍药、(S)-补骨脂二氢黄酮、新补骨脂异黄酮可通过花生四烯酸途径发挥治疗作用。此外，WB和ELISA结果表明，BHC可以抑制肺组织中COX2和5-LOX的表达，并抑制血清样品中AA及其代谢物的生成。花生四烯酸代谢途径的调节可能是BHC治疗COPD的重要机制。
结论
综上所述，研究表明BHC通过花生四烯酸代谢途径发挥抗炎和抗氧化特性，对COPD模型大鼠具有保护作用。该研究为BHC在慢阻肺治疗中的应用提供了有益的支持。
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