经典名方阳和汤的抗乳腺癌活性成分筛选  

Screening of Anti-breast Cancer Active Ingredients in Famous Classical Formula Yanghetang

作　　者：苏思佳 赵鑫宇 周静娜 高俊峰[1] 唐旭[1] 温彬宇[1] SU Sijia;ZHAO Xinyu;ZHOU Jingna;GAO Junfeng;TANG Xu;WEN Binyu(Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东方医院,北京100078

出　　处：《中国实验方剂学杂志》2025年第8期21-30,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：北京市中医药科技发展资金项目(JJ-2020-39)。

摘　　要：目的:基于超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS),将血清药物化学、血清药物成分响应特征、网络药理学及药物相似性预测等方法相结合,筛选经典名方阳和汤抗乳腺癌潜在活性成分。方法:采用UPLC-QTOF-MS/MS鉴别阳和汤不同溶剂(甲醇、50%甲醇、水)提取物中的主要成分,并分析雌性SD大鼠给药0.5、1、2 h后含药血清的入血成分,结合UNIFI 1.8.2软件所得血清药物成分响应特征值进一步筛选入血原型成分及代谢产物,得到具有显著消长规律的阳和汤入血成分。应用网络药理学构建“药物-成分-通路-靶点-疾病”网络,将阳和汤入血成分和乳腺癌关键靶点进行分子对接并通过SwissADME数据库分析其药物相似性。结果:阳和汤样品经过不同溶剂提取后共鉴定出42个化合物,其中16个化合物为3种不同提取溶剂共有成分。阳和汤入血成分共16种,其中含5种原型药物和11种代谢产物。网络药理学分析表明,阳和汤治疗乳腺癌涉及禽肉瘤病毒致癌基因同源物(SRC)、表皮生长因子受体(EGFR)、磷脂酰肌醇3-激酶催化亚基α(PIK3CA)等15个关键靶点。分子对接显示,16个潜在活性成分与预测作用靶点结合良好,结合药物相似性分析,最终鉴定阳和汤入血成分中12个化合物具有抗乳腺癌活性潜质,主要包括α-蒎烯、γ-桉叶醇及其代谢产物,其中1种来自麻黄,1种来自熟地黄,8种来自肉桂。结论:阳和汤化学成分主要包括多糖类、单萜苷类和香豆素类等化合物,其原型成分入血后主要发生氧化、水解及乙酰化等反应,其抗乳腺癌机制可能与调控丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)等信号通路有关。该研究结果可为进一步探索阳和汤治疗乳腺癌奠定理论基础。Objective:Based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS),the combination of serum pharmacochemistry,response profile of absorbed components in serum,network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer.Methods:UPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang,and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5,1,2 h of administration.Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2,the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth.Network pharmacology was applied to construct a drug-component-pathway-target-disease network,and molecular docking was performed between absorbed components and key targets of breast cancer,and the drug similarity was analyzed by SwissADME.Results:Forty-two compounds were identified in Yanghetang samples extracted with different solvents,of which 16 compounds were common to the three different extraction solvents(methanol,50%methanol and water).The results of drug-containing serum analysis showed that there were 16 absorbed components in serum,including 5 prototypes and 11 metabolites.Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src(SRC),epidermal growth factor receptor(EGFR)and phosphoinositide 3 kinase catalytic alpha polypeptide(PIK3CA).Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets.Combined with drug likenesses,12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity,mainly includingα-pinene andγ-eudesmol and their metabolites,of

关 键 词：中医药 活性成分 乳腺癌 阳和汤 网络药理学 分子对接 药物相似性 超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS) 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R271.1[理学—分析化学] O657[理学—化学] R73