目的 采用網(wǎng)絡(luò)藥理學方法研究金銀花抗肺癌的主要有效成分和潛在作用靶點，探討其“多成分-多靶點-多通路”的抗肺癌作用機制。方法 通過PubMed、TCMSP數(shù)據(jù)庫篩選金銀花的主要活性成分和相關(guān)成分的作用靶點，并把口服生物利用度（OB）≥20%和類藥性（DL）≥0.1作為篩選金銀花活性成分的條件。通過CTD在線數(shù)據(jù)庫檢索與肺癌有關(guān)的作用靶點，采用String數(shù)據(jù)庫分別構(gòu)建金銀花成分靶點和肺癌相關(guān)作用靶點的PPI網(wǎng)絡(luò)圖，并利用cytoscape 3.7獲得兩個PPI網(wǎng)絡(luò)圖的交集網(wǎng)絡(luò)，篩選出與肺癌有關(guān)的關(guān)鍵作用靶點。最后對關(guān)鍵靶點進行通路富集分析研究其作用的信號通路。結(jié)果 金銀花治療肺癌的主要活性成分有槲皮素、芹黃素、山柰酚、毛地黃黃酮等。金銀花與肺癌相關(guān)的潛在作用靶點有38個，如PON1、NQO1、AHR、MMP10、CYP1A2、CYP1B1、GJA1、NOS2、RXRA、IL10等。共富集出18條與以上38個關(guān)鍵靶點有關(guān)的信號通路，如膀胱癌、細胞色素p450氧化酶、甲狀腺癌、小細胞肺癌、子宮內(nèi)膜癌等。此外，金銀花還參與調(diào)節(jié)炎癥反應(yīng)、脂質(zhì)代謝、細胞凋亡等生物過程，顯示了金銀花“多成分-多靶點-多通路”共同發(fā)揮協(xié)同作用的特點。結(jié)論 為研究金銀花抗肺癌的藥效物質(zhì)基礎(chǔ)和作用機制提供新思路，為金銀花的進一步開發(fā)應(yīng)用提供了科學依據(jù)。

Objective The main effective components and action pathway of Lonicera japonica against lung cancer were studied by network pharmacology, to explore the anti-lung cancer mechanism of "multi-component-multi-target-multi-pathway". Methods PubMed and TCMSP databases were used to screen the main active ingredients of Lonicera japonica, and oral bioavailability (OB) ≥ 20%and chemotherapy-like (DL) ≥ 0.1 were used as the conditions for screening the active components of Lonicera japonica, then Cytoscape 3.7 was used to construct the network diagram of "component-target". PPI network graph between honeysuckle component targets and lung cancer related targets was constructed through CTD and String database, then the intersection network of the two PPI network graphs was analyzed. Results The main active ingredients of Lonicera japonica in treatment of lung cancer include quercetin, coniferin, kaempferol and foxglove and so on. It may act on 38 lung cancer related targets, such as PON1, NQO1, AHR, MMP10, CYP1A2, CYP1B1, GJA1, NOS2, RXRA, IL10 and so on. It was regulated by 18 signaling pathways including bladder cancer, cytochrome P450, drug metabolism-cytochrome p450, thyroid cancer and endometrial cancer and so on. The results showed that Lonicera japonica anti-lung cancer "multi-component-multi-target-multi-pathway" action mechanism characteristics. Conclusions This study provides a scientific basis for the analysis of the mechanism of action of Lonicera japonica in the treatment of lung cancer, and points out the direction for the further experimental confirmation of the anti-lung cancer target and its signaling pathway of the active components of Lonicera japonica.

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