目的 基于指紋圖譜和網(wǎng)絡(luò)藥理學(xué)方法，分析預(yù)測樹參Dendropanax dentiger的差異活性成分，并建立其定量分析方法，為樹參的質(zhì)量控制提供參考。方法 采用HPLC法建立樹參的指紋圖譜并結(jié)合化學(xué)計量學(xué)篩選不同產(chǎn)地樹參的主要差異成分。通過網(wǎng)絡(luò)藥理學(xué)方法，確定樹參特征成分治療類風(fēng)濕關(guān)節(jié)炎（rheumatoid arthritis，RA）的核心靶點和關(guān)鍵通路，繪制“成分-核心靶點-通路”網(wǎng)絡(luò)圖，以預(yù)測樹參抗RA的差異活性成分。以28批樹參藥材為研究對象，對其差異活性成分進行含量測定，確定出樹參的差異活性成分。結(jié)果 建立了28批樹參藥材的指紋圖譜，標定了13個共有峰，并指認出5個共有峰，分別為原兒茶酸、紫丁香苷、綠原酸、異綠原酸A、異綠原酸C。通過化學(xué)計量學(xué)分析，初步篩選出紫丁香苷、綠原酸、異綠原酸A和異綠原酸C為主要差異性成分。網(wǎng)絡(luò)藥理學(xué)分析顯示，紫丁香苷、綠原酸、異綠原酸A、異綠原酸C可能通過前列腺素內(nèi)過氧化物合酶2（prostaglandin-endoperoxide synthase 2，PTGS2）、半胱天冬酶-3（Caspase-3，CASP3）、表皮生長因子受體（epidermal growth factor receptor，EGFR）、基質(zhì)金屬蛋白酶-2 （matrix metalloproteinase-2，MMP2）、基質(zhì)金屬蛋白酶-3（matrix metalloproteinase-3，MMP3）、E-選擇素（E-selectin，SELE）、P-選擇素（P-selectin，SELP）、前列腺素內(nèi)過氧化物合酶1 （prostaglandin-endoperoxide synthase 1，PTGS1）8個核心靶點，影響脂質(zhì)與動脈粥樣硬化、腎素-血管緊張素系統(tǒng)、白細胞介素-17（interleukin-17，IL-17）和腫瘤壞死因子（tumor necrosis factor，TNF）等信號通路，從而發(fā)揮治療RA的作用。最終確定紫丁香苷、綠原酸、異綠原酸A、異綠原酸C可作為樹參治療RA的差異活性成分。結(jié)論 建立的質(zhì)量評價方法準確可靠，結(jié)合網(wǎng)絡(luò)藥理學(xué)篩選出的差異活性成分可為樹參質(zhì)量控制提供依據(jù)，并為其治療RA的作用機制提供參考。

Objective To analyze and predict the differential active components of Dendropanax dentiger using fingerprint and network pharmacology methods, establish quantitative analysis methods, and provide a reference for the quality control of D. dentiger. Methods High-performance liquid chromatography (HPLC) was used to establish the fingerprint of D. dentiger, and chemometric analysis was employed to screen the main differential components from different origins. Furthermore, network pharmacology was applied to identify the core targets and key pathways of the characteristic components of D. dentiger in the treatment of rheumatoid arthritis (RA). A “component-core target-pathway” network was constructed to predict the differential active components of D. dentiger for anti-RA effects. The content of the differential active components was determined in 28 batches of D. dentiger samples, and the final differential active components were identified. Results The HPLC fingerprint of 28 batches of D. dentiger samples was established, with 13 common peaks identified, including 5 peaks assigned as protocatechuic acid, syringin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C. Chemometric analysis preliminarily identified syringin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C as the main differential components. Network pharmacology analysis revealed that syringin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C might exert therapeutic effects on RA through 8 core targets, including prostaglandin-endoperoxide synthase 2 (PTGS2), caspase 3 (CASP3), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-3 (MMP3), E-selectin (SELE), P-selectin (SELP), and prostaglandin-endoperoxide synthase 1 (PTGS1), influencing signaling pathways such as lipid and atherosclerosis, renin-angiotensin system, interleukin-17 (IL-17), and tumor necrosis factor (TNF). Finally, syringin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were determined as the differential active components of D. dentiger for the treatment of RA. Conclusion The established quality evaluation method is accurate and reliable. The differential active components screened by network pharmacology provide a basis for the quality control of D. dentiger and insights into its mechanism of action in treating RA.

R286.2

麗水市自籌類公益性技術(shù)應(yīng)用研究項目（2022SJZC037）；浙江省中醫(yī)藥管理局共建科技計劃項目（GZY-ZJ-KJ-23098）；浙江省中醫(yī)藥科技計劃項目（2024ZR205）；靈澤片主成分溫莪術(shù)藥材質(zhì)量提升及其真實世界臨床研究（KJHX2206）