阴阳火及其成分治疗慢性阻塞性肺疾病:临床前证据及可能机制。

Wang Yide, Gao Zhen
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引用次数: 0

摘要

目的:结合meta分析和生物信息学策略,初步探讨阴阳火及其提取物治疗慢性阻塞性肺疾病(COPD)的潜在机制。方法:首先进行meta分析。采用主题词与游离词相结合的系统策略,检索阴阳火治疗COPD的中英文文献。采用sycle风险偏倚评估工具对纳入的研究进行评价,评价后使用评价管理软件合并效应量进行统计分析。然后,基于生物信息学技术,筛选阴阳火()的有效成分及其靶点,并与COPD靶点作图比较,获得交叉基因。构建“药材-化合物-靶点模型”,并对关键通路进行标注。最后,将核心靶点与重要化合物对接。结果:meta分析共纳入8项研究。结果显示,阴阳火组可显著下调COPD模型中肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-8等促炎因子的表达,提高IL-10、磷酸化蛋白激酶B (P - akt)等抗炎因子和抗氧化因子的表达(均P < 0.05)。通过生物信息学技术共获得阴阳火(草本淫羊藿)的23个有效成分和102个对应的靶基因,其中17个化合物和63个靶点与COPD密切相关。富集分析结果主要包括TNF信号通路、PI3K /Akt信号通路、肿瘤信号通路以及其他炎症反应、氧化应激、肿瘤相关通路。分子对接结果表明,24- epicamstreol前5个组分与IL-6等10个核心靶点的结合能分数均小于-5.0 kcal/mol,具有较好的结合能力。结论:荟萃分析和生物信息学结果提示阴阳火及其成分对COPD的治疗作用可能与拮抗炎症和氧化应激有关。以上研究结果为阴阳火作为防治慢性阻塞性肺病的天然药物的开发提供了初步依据。
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Yinyanghuo () and its components for chronic obstructive pulmonary disease: preclinical evidence and possible mechanisms.

Objective: To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo () and its extract in treating chronic obstructive pulmonary disease (COPD).

Methods: First, Meta-analysis was carried out. The Chinese and English literature of Yinyanghuo () in treating COPD was searched using the systematic strategy of combining subject words with free words. The included studies were evaluated by the SYRCLE risk bias assessment tool, after which the review manager software was used to combine the effect quantities for statistical analysis. Then, based on bioinformatics technology, the active ingredients and their targets of Yinyanghuo () were screened, and the intersection genes were obtained by mapping and comparing with the targets of COPD. The "medicinal materials-compounds-targets model" was constructed, and the key pathways were annotated. Finally, the core target was docked with important compounds.

Results: A total of 8 studies were included in the Meta-analysis. The results showed that the Yinyanghuo (Herba Epimedii Brevicornus) group could significantly down-regulate pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B (p-AKT) in the COPD model (all P < 0.05). A total of 23 active components and 102 corresponding target genes of Yinyanghuo (Herba Epimedii Brevicornus) were obtained by bioinformatics technology, among which 17 compounds and 63 targets were closely related to COPD. The results of enrichment analysis mainly included TNF signaling pathway, phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, cancer signaling pathway, and other inflammatory reactions, oxidative stress, and tumor-related pathways. The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such as IL-6 were all less than ﹣5.0 kcal/mol, suggesting good binding ability.

Conclusions: Meta-analysis and bioinformatics results indicated that the therapeutic effect of Yinyanghuo () and its components on COPD might be related to antagonizing inflammation and oxidative stress. The above findings provide a preliminary basis for the development of Yinyanghuo () as a natural drug for preventing and treating COPD.

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