A Combined Phytochemistry and Network Pharmacology Approach to Reveal the Effective Substances and Mechanisms of Wei-Fu-Chun Tablet in the Treatment of Precancerous Lesions of Gastric Cancer

被引：37

作者：

Wang, Huijun ^{[1
,2
,3
,4
]}

Wu, Ruoming ^{[2
]}

Xie, Dong ^{[1
]}

Ding, Liqin ^{[5
]}

Lv, Xing ^{[2
]}

Bian, Yanqin ^{[1
]}

Chen, Xi ^{[1
]}

Lena, Bahaji Azami Nisma ^{[1
]}

Wang, Shunchun ^{[3
,4
]}

Li, Kun ^{[2
]}

Chen, Wei ^{[6
]}

Ye, Guan ^{[2
]}

Sun, Mingyu ^{[1
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Inst Liver Dis, Shuguang Hosp, Key Lab Liver & Kidney Dis,Minist Educ, Shanghai, Peoples R China

[2] Shanghai Pharmaceut Holding Co Ltd, Cent Res Inst, Shanghai, Peoples R China

[3] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai, Peoples R China

[4] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, SATCM Key Lab New Resources & Qual Evaluat Chines, Shanghai, Peoples R China

[5] Shanghai Zhonghua Pharmaceut Co Ltd, Shanghai, Peoples R China

[6] Huqingyutang Chinese Med Modernizat Res Inst Zhej, Hangzhou, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2020年 / 11卷

基金：

上海市自然科学基金;

关键词：

Wei-Fu-Chun tablet; precancerous lesions of gastric cancer; network pharmacology; effective substances and mechanism; UHPLC-ESI-Q-TOF; MS; OF-FLIGHT MASS; ELECTROSPRAY-IONIZATION; RAT SERUM; LC-MS/MS; NARINGIN; IDENTIFICATION; CONSTITUENTS; DITERPENOIDS; METABOLITES; ACTIVATION;

D O I：

10.3389/fphar.2020.558471

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Wei-Fu-Chun (WFC) tablet is a commercial medicinal product approved by China Food and Drug Administration, which is made of Panax ginseng C.A.Mey., Citrus aurantium L., and Isodon amethystoides (Benth.). WFC has been popularly used for the treatment of precancerous lesions of gastric cancer (PLGC) in clinical practice. In this study, a UHPLC-ESI-Q-TOF/MS method in both positive and negative ion mode was employed to rapidly survey the major constituents of WFC. 178 compounds including diterpenoids, triterpenes, sesquiterpenes, flavonoids, saponins, phenylpropanoids, lignans, coumarins, organic acids, fatty acids, quinones, and sterols, were identified by comparing their retention times, accurate mass within 5 ppm error, and MS fragmentation ions. In addition, 77 absorbed parent molecules and nine metabolites in rat serum were rapidly characterized by UHPLC-ESI-Q-TOF/MS. The network pharmacology method was used to predict the active components, corresponding therapeutic targets, and related pathways of WFC in the treatment of PLGC. Based on the main compounds in WFC and their metabolites in rat plasma and existing databases, 13 active components, 48 therapeutic targets, and 61 pathways were found to treat PLGC. The results of PLGC experiment in rats showed that WFC could improve the weight of PLGC rats and the histopathological changes of gastric mucosa partly by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathway to increase pepsin secretion. This study offers an applicable approach to identify chemical components, absorbed compounds, and metabolic compounds in WFC, and provides a method to explore bioactive ingredients and action mechanisms of WFC.

引用

页数：20

共 38 条

[1] Cancer Statistics in China, 2015 [J].

Chen, Wanqing ;

Zheng, Rongshou ;

Baade, Peter D. ;

Zhang, Siwei ;

Zeng, Hongmei ;

Bray, Freddie ;

Jemal, Ahmedin ;

Yu, Xue Qin ;

He, Jie .

CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132

[2]

CORREA P, 1975, LANCET, V2, P58

[3] A Rapid Ultra-performance Liquid Chromatography-Electrospray Ionisation Mass Spectrometric Method for the Analysis of Saponins in the Adventitious Roots of Panax notoginseng [J].

Dan, Mo ;

Xie, Guoxiang ;

Gao, Xianfu ;

Long, Xiangbao ;

Su, Mingming ;

Zhao, Aihua ;

Zhao, Tie ;

Zhou, Mingmei ;

Qiu, Yunping ;

Jia, Wei .

PHYTOCHEMICAL ANALYSIS, 2009, 20 (01) :68-76

[4] Genomic Profiling of HER2-Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2-Positive Advanced Gastric Cancer Treated with Trastuzumab [J].

Diaz-Serrano, Asuncion ;

Angulo, Barbara ;

Dominguez, Carolina ;

Pazo-Cid, Roberto ;

Salud, Antonieta ;

Jimenez-Fonseca, Paula ;

Leon, Ana ;

Carmen Galan, Maria ;

Alsina, Maria ;

Rivera, Fernando ;

Plaza, J. Carlos ;

Paz-Ares, Luis ;

Lopez-Rios, Fernando ;

Gomez-Martin, Carlos .

ONCOLOGIST, 2018, 23 (09) :1092-1102

[5] Determination of flavone, flavonol, and flavanone aglycones by negative ion liquid chromatography electrospray ion trap mass spectrometry [J].

Fabre, N ;

Rustan, I ;

de Hoffmann, E ;

Quetin-Leclercq, J .

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, 2001, 12 (06) :707-715

[6] Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways [J].

Gao, Hongwei ;

Kang, Naixin ;

Hu, Chao ;

Zhang, Ziyu ;

Xu, Qiongming ;

Liu, Yanli ;

Yang, Shilin .

PHYTOMEDICINE, 2020, 69

[7] The role of FoxO in the regulation of metabolism [J].

Gross, D. N. ;

van den Heuvel, A. P. J. ;

Birnbaum, M. J. .

ONCOGENE, 2008, 27 (16) :2320-2336

[8] Network pharmacology: the next paradigm in drug discovery [J].

Hopkins, Andrew L. .

NATURE CHEMICAL BIOLOGY, 2008, 4 (11) :682-690

[9]

Huang Xuan, 2014, Zhongguo Zhong Xi Yi Jie He Za Zhi, V34, P450

[10] Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Weifuchun tablet [J].

Jin, Yiran ;

Tian, Tingting ;

Ma, Yinghua ;

Xu, Huijun ;

Du, Yingfeng .

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2015, 1000 :112-119

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