基于LC-MS结合网络药理学探讨参白解毒方抗结直肠腺瘤癌变成分及作用机制  

Exploring the Components and Mechanism of Shenbai Jiedu Decoction in Treating CRA Carcinogenesis Based on LC-MS and Network Pharmacology

作　　者：刘丽 闫秋莹 范晓萱 范旻旻 李柳 陶李蕙苹[1,2,3] 常澍晨 程海波 孙东东 LIU Li;YAN Qiuying;FAN Xiaoxuan;FAN Minmin;LI Liu;TAO-LI Huiping;CHANG Shuchen;CHENG Haibo;SUN Dongdong(Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor,Nanjing 210023,China;The First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China;The Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]江苏省中医药防治肿瘤协同创新中心,江苏南京210023 [2]南京中医药大学第一临床医学院,江苏南京210023 [3]南京中医药大学附属医院,江苏南京210029

出　　处：《南京中医药大学学报》2024年第8期771-784,共14页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074318,82374287);国家自然科学基金重点项目(81930117);江苏省科技计划项目(BK20230452);江苏省中医药科技发展计划项目(ZD202201);江苏省研究生科研创新计划(KYCX23_2203)。

摘　　要：目的解析治疗结直肠腺瘤(CRA)的临床验方参白解毒方(SBJDD)化学成分并探究其防治CRA癌变的潜在机制。方法建立超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF-MS)检测方法,分析SBJDD水煎液及口服该方大鼠的血浆样品中化学成分;基于网络药理学方法筛选SBJDD在CRA癌变不同阶段的潜在活性成分,探究其抗CRA癌变作用机制;开展体外实验验证SBJDD抗CRC作用机制。结果在SBJDD水煎液和大鼠口服该方后的血浆样品中分别鉴定出152和41种化学成分。网络药理学结果表明,在结直肠上皮炎症(CREI)阶段,SBJDD中潜在活性成分Epiberberine和Kushenol H等可能通过作用于PIK3CA、MAPK3和PIK3CB等靶点,影响PI3K-AKT和Ras等信号通路,调控与蛋白质磷酸化和信号转导等相关的生物过程;在CRA阶段,该方中活性成分3,7-Dihydroxycoumarin、Palmatine和Kushenol A等可能通过靶向AKT和EGFR等靶点,影响HIF-1、Rap1等信号通路,调控细胞凋亡和细胞增殖等生物过程;在CRA癌变阶段,3,7-Dihydroxycoumarin等潜在活性成分可能通过作用于TP53等靶点,影响PI3K-AKT和甲状腺激素等信号通路,调控RNA聚合酶Ⅱ启动子转录和细胞凋亡等生物过程;在CRC阶段,p-Coumaric acid等潜在活性成分通过作用于PRKCB等靶点,影响EGFR酪氨酸激酶抑制剂耐药性和PI3K-AKT等信号通路,调控细胞凋亡和信号转导等生物过程。体外研究表明,SBJDD显著抑制HT29细胞增殖,并抑制EG-FR和PKC蛋白的表达。结论SBJDD中化学成分主要由生物碱、有机酸和黄酮类成分组成,方中成分在CRA癌变的不同阶段中与不同的靶点结合,调节相关的信号通路,产生治疗效果。OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction SBJDD a traditional Chinese cine medi-TCM prescription clinically used for the treatment of colorectal adenoma CRA and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry UPLC-Q-TOF-MS method was established to detect the chemical components in the decoction of SBJDD and the ma plas-samples of rats after administration with SBJDD.Based on the network pharmacological method SBJDD was screened for the potential active ingredients at different stages of CRA carcinogenesis and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer CRC action of SBJDD.RESULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage the potential active ingredients in SBJDD including epiberberine and kushenol H might affect target proteins such as PIK3CA MAPK3 and PIK3CB.This in turn can influence signaling pathways like PI3K-AKT and Ras signaling pathways and regulate biological processes like protein phosphorylation and signal transduction.During the CRA stage the potential active ingredi-ents from SBJDD such as 37-dihydroxycoumarin palmatine and kushenol A might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process and positive regulation of cell proliferation and modify HIF-1 and Rap1 signaling pathways.During the progression of CRA carcinogenesis potential active ingredients such as 37-dihydroxycouma-rin may interact with TP53 and impact the PI3K-AKT and Thyroid hormone signaling pathways to regulate biological processes in-cluding positive regulation of transcription from RNA polymeraseⅡp

关 键 词：参白解毒方 结直肠腺瘤癌变 UPLC-Q-TOF-MS 网络药理学 

分 类 号：R285.5[医药卫生—中药学]