目的 采用網(wǎng)絡(luò)藥理學(xué)研究藤黃健骨膠囊治療骨性關(guān)節(jié)炎的有效活性成分及主要作用機(jī)制。方法 采用TCMSP、Uniport、DrugBank數(shù)據(jù)庫檢索藤黃健骨膠囊的主要化學(xué)成分及作用靶點(diǎn)；基于DisGeNET、DrugBank、OMIM及Genecards數(shù)據(jù)庫獲取骨性關(guān)節(jié)炎的相關(guān)靶點(diǎn)；將藤黃健骨膠囊與骨性關(guān)節(jié)炎的靶點(diǎn)取交集，獲取藤黃健骨膠囊治療骨性關(guān)節(jié)炎的直接靶點(diǎn)；利用STRING數(shù)據(jù)庫得到蛋白相互作用（PPI）網(wǎng)絡(luò)；使用DAVID數(shù)據(jù)庫進(jìn)行GO和KEGG富集分析；采用Cytoscape 3.7.2軟件構(gòu)建PPI網(wǎng)絡(luò)、“藥物-活性成分-靶點(diǎn)”網(wǎng)絡(luò)和“活性成分–重要靶點(diǎn)–關(guān)鍵通路”網(wǎng)絡(luò)，并進(jìn)行相關(guān)網(wǎng)絡(luò)分析。結(jié)果 初步篩選藤黃健骨膠囊69個(gè)成分和257個(gè)靶點(diǎn)；骨性關(guān)節(jié)炎2 655個(gè)靶點(diǎn)，藥物-疾病交集靶點(diǎn)143個(gè)；經(jīng)過PPI、GO和KEGG富集及相關(guān)網(wǎng)絡(luò)分析，最終得到藥物的主要藥效成分有槲皮素、木犀草素、山柰酚、β-谷甾醇、芒柄花黃素、甘草查爾酮A、淫羊藿苷元等；關(guān)鍵靶點(diǎn)為PTGS2、TNF、PTGS1、PIK3CG、VEGFA、AKT1、ADRB2、MAPK1、ESR1、MMP2、IL-6、TGFB1等；映射的靶標(biāo)通路為PI3K-Akt信號(hào)通路、NF-κB信號(hào)通路、MAPK信號(hào)通路、Toll樣受體信號(hào)通路、破骨細(xì)胞分化、FoxO信號(hào)通路、HIF-1信號(hào)通路、NOD樣受體信號(hào)通路、雌激素信號(hào)通路等；涉及的生物過程主要有凋亡過程的負(fù)調(diào)控、炎癥反應(yīng)、對(duì)缺氧的反應(yīng)、對(duì)雌二醇的反應(yīng)、細(xì)胞對(duì)缺氧的反應(yīng)、ERK1和ERK2級(jí)聯(lián)的正調(diào)控、一氧化氮生物合成過程的正調(diào)控等。結(jié)論 藤黃健骨膠囊主要通過抑制炎癥反應(yīng)、抑制軟骨細(xì)胞凋亡、調(diào)節(jié)骨代謝、保護(hù)軟骨機(jī)制及調(diào)節(jié)軟骨下骨代謝平衡途徑發(fā)揮治療骨關(guān)節(jié)炎作用。

Objective To study the active ingredients and main mechanism of Tenghuang Jiangu Capsules in treatment of osteoarthritis based on network pharmacology. Methods Using TCMSP, Uniport, DrugBank databases, the chemical constituents and targets of Tenghuang Jiangu Capsules were screened. Using DisGeNET, and DrugBank, OMIM, and GeneCards databases, the targets of osteoarthritis were retrieved. The intersection of the target of Tenghuang Jiangu Capsules and osteoarthritis was taken to obtain the direct target of the treatment of osteoarthritis with Tenghuang Jiangu Capsules. Protein interaction (PPI) relationship was obtained by using String database. GO analysis and KEGG enrichment analysis were conducted by using the database of DAVID. Cytoscape 3.7.2 software were used to construct and analyse the networks of Protein-protein interaction, "medicine-active components-targets" and "active components-important targets-critical pathways". Results Tenghuang Jiangu Capsules had 69 components and 257 targets. There were 2 655 targets for osteoarthritis and 143 drug-disease intersection targets. Through PPI, GO, KEGG, and related network analysis, the main pharmacodynamic components of the drug were obtained, including quercetin, luteolin, kaempferol, β-sitosterol, formononetin, licorice chalcone A, icariin, etc. The key targets were PTGS2, TNF, PTGS1, PIK3CG, VEGFA, AKT1, ADRB2, MAPK1, ESR1, MMP2, IL-6, TGFB1, etc. The key pathways were PI3K-Akt signaling pathway, NF-κB signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, osteoclast differentiation, FoxO signaling pathway, HIF-1 signaling pathway, NOD receptor signaling pathway, estrogen signaling pathway, etc. The biological processes involved mainly include negative regulation of apoptosis, inflammation, response to hypoxia, response to estradiol, cell response to hypoxia, positive regulation of ERK1 and ERK2 cascade, positive regulation of nitric oxide biosynthesis, etc. Conclusion Tenghuang Jiangu Capsules mainly plays a role in treating osteoarthritis by inhibiting inflammatory reaction, inhibiting chondrocyte apoptosis, regulating bone metabolism, protecting cartilage mechanism and regulating subchondral bone metabolism balance.

R285

河南省科技發(fā)展計(jì)劃項(xiàng)目（202102310191）；河南省高等學(xué)校重點(diǎn)科研項(xiàng)目計(jì)劃（19A320070，21A360026）