目的 通過系統(tǒng)藥理學方法探索裸花紫珠有效成分的藥理作用機制。方法 運用文獻搜索和TCMSP數(shù)據(jù)庫，建立裸花紫珠活性分子數(shù)據(jù)庫，通過對數(shù)據(jù)庫中的120個分子從口服利用度、類藥性分析等幾個方面進行篩選，預測出有潛在活性的分子，并通過王永華教授團隊研發(fā)的SYSDT以及WES技術進行靶標預測，進而通過藥物-靶標預測模型Sys TD、Drug Bank數(shù)據(jù)庫等構建靶標-疾病-通路網(wǎng)絡圖，并借助基因本位論（GO）分析裸花紫珠有效成分參與的生物學過程。結果 裸花紫珠中黃酮類化合物如木犀草素及其衍生物、甲基鼠李素和芹菜素等作用于較多的靶點，在裸花紫珠的藥效中起著關鍵作用；其對炎癥、癌癥、心血管疾病、神經(jīng)系統(tǒng)以及免疫系統(tǒng)均有影響，其中ABCB1、NOS3、MAPK14、PPARG、GSK3β、PTGS2等同時靶向治療多種類型疾病和多種生物學通路。GO分析表明了裸花紫珠對炎癥反應、凝血、血管生成、鈣離子信號傳導、血壓等具有調節(jié)作用。結論 裸花紫珠黃酮類化合物在的藥效中起關鍵作用，通過ABCB1、NOS3、MAPK14等靶點對炎癥反應、凝血、血管生成、鈣離子信號傳導、血壓等發(fā)揮調節(jié)作用。

Objective In this study, the method of systems pharmacology was used to explore the pharmacological mechanism of Callicarpa nudiflora. Methods The active molecule database of C. nudiflora was established by literature searching and TCMSP database. A total of 120 molecules were screened according to oral availability, drug-likeness analysis, blood brain barrier, and halflife to predict potential active molecules and targets based on SYSDT and WES technique established by Pro. Yonghua Wang. Screening was conducted from several aspects, including drug-target prediction model Sys TD, potential target prediction, disease analysis, network pharmacology analysis and GO analysis. Results Through the oral bioavailability, drug-likeness and blood-brain barrier analysis, 28 compounds were identified as effective active ingredients, including ones reported in the literature. There were 112 targets related to the 28 compounds, and the drug-target network revealed that Molecule M029 (luteolin) and its derivatives,Molecule M040 (apigenin) and M042 (rhamnazin) had a relatively high degree, they play significant roles in the drug-target network. The target-disease-pathways network analysis suggested that C. nudiflora had a good therapeutic effect on diseases including cancer, inflammation, metabolic disease, immune system disease, blood disease, cardiovascular disease, nervous system disease and bacterial infection. The GO analysis discovered that C. nudiflora had regulatory effects on cell proliferation, cell apoptosis, intracellular calcium concentration, inflammatory reaction, platelet activation, coagulation and angiogenesis, etc. In addition, the target NOS3, MAPK14, PIK3CG et al. were linked to a variety of diseases and biologic process. Conclusions Flavonoids from Callicarpa nudiflora play a key role in the pharmacodynamics. They regulate inflammation, coagulation, angiogenesis, calcium signal transduction and blood pressure through ABCB1, NOS3, MAPK14 and other targets.

海南省財政科技計劃資助（ZDYF2018228）