Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma

HUANG Ruyi; LI Jinyu; LIN Wenqi; JIANG Xin; CHEN Yanling; HUANG Weikun; YANG Lin

doi:10.6039/j.issn.1001-0408.2026.02.05

您当前的位置：

首页 >

文章列表页 >

Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma

更新时间：2026-02-10

- Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma
- ZHONGGUO YAOFANG Vol. 37, Issue 2, Pages: 161-167(2026)
- 作者机构：
  
  1.福建医科大学肿瘤临床医学院/福建省肿瘤医院药学部，福州　350011
  2.福州大学化学学院，福州　350108
  3.福建中医药大学药学院，福州　350122
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.02.05
  CLC： R965;R733.4
- Received：08 September 2025，
  
  Revised：2025-10-15，
  
  Accepted：26 December 2025，
  
  Published：30 January 2026
- 稿件说明：
移动端阅览
黄茹意,李金宇,林文琪,等.西黄丸抗弥漫大B细胞淋巴瘤的作用机制预测与验证[J].中国药房,2026,37(02):161-167.

HUANG Ruyi,LI Jinyu,LIN Wenqi,et al.Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma[J].ZHONGGUO YAOFANG,2026,37(02):161-167.
黄茹意,李金宇,林文琪,等.西黄丸抗弥漫大B细胞淋巴瘤的作用机制预测与验证[J].中国药房,2026,37(02):161-167. DOI： 10.6039/j.issn.1001-0408.2026.02.05.

HUANG Ruyi,LI Jinyu,LIN Wenqi,et al.Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma[J].ZHONGGUO YAOFANG,2026,37(02):161-167. DOI： 10.6039/j.issn.1001-0408.2026.02.05.

摘要

目的

探讨西黄丸抗弥漫大B细胞淋巴瘤（DLBCL）的作用机制。

方法

基于TCMSP、GeneCards、DisGeNET等数据库筛选西黄丸活性成分及DLBCL相关疾病靶点；利用String数据库和Cytoscape软件，构建蛋白质-蛋白质相互作用网络以筛选核心成分与核心靶点，然后进行基因本体功能和京都基因与基因组数据库通路富集分析；利用GEPIA和PanCanSurvPlot数据库分析核心靶点的临床相关性；进一步对核心成分与核心靶点进行分子对接和分子动力学模拟验证，并采用分子力学泊松-玻尔兹曼表面积（MM-PBSA）算法计算结合自由能。采用CCK-8法、流式细胞术及Western blot法验证西黄丸对DLBCL的作用及相关分子机制。

结果

网络药理学共筛选出108个西黄丸活性成分和410个西黄丸治疗DLBCL的潜在靶点，获得17 beta-estradiol（17

-雌二醇）、quercetin（槲皮素）等6个核心成分，肿瘤蛋白53（TP53）、酪氨酸蛋白激酶Src（SRC）等10个核心靶点。富集分析显示，西黄丸抗DLBCL主要涉及凋亡信号通路、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路等。临床相关性分析显示，TP53、SRC在DLBCL样本中高表达，且与患者不良预后相关（

＜0.05）。分子对接、分子动力学模拟及MM-PBSA结合自由能计算证实，SRC-槲皮素复合物具有更强而稳定的结合亲和力。体外实验结果显示，西黄丸可浓度依赖性抑制DLBCL细胞的增殖；与对照组比较，西黄丸中、高浓度组可显著诱导SU-DHL2和SU-DHL4细胞凋亡，显著降低SU-DHL4细胞中SRC蛋白、磷酸化PI3K（p-PI3K）/PI3K、p-Akt/Akt的表达（

＜0.05）。

结论

西黄丸可能通过调控SRC/PI3K/Akt信号通路抑制DLBCL细胞增殖并诱导其凋亡。

Abstract

OBJECTIVE

To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）.

METHODS

The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot.

RESULTS

Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）

]

were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （

＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a stronger and more stable binding affinity.

In vitro

experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down-regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （

＜0.05）.

CONCLUSIONS

XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

关键词

Keywords

references

BARRACLOUGH A ， HAWKES E ， SEHN L H ， et al . Diffuse large B-cell lymphoma [J ] . Hematol Oncol ， 2024 ， 42 （ 6 ）： e3202 .

WANG L ， LI L R ， YOUNG K H . New agents and regimens for diffuse large B cell lymphoma [J ] . J Hematol Oncol ， 2020 ， 13 （ 1 ）： 175 .

CRUMP M ， NEELAPU S S ， FAROOQ U ， et al . Outcomes in refractory diffuse large B-cell lymphoma：results from the international SCHOLAR-1 study [J ] . Blood ， 2017 ， 130 （ 16 ）： 1800 - 1808 .

ZHANG J ， GU Y ， CHEN B A . Drug-resistance mechanism and new targeted drugs and treatments of relapse and refractory DLBCL [J ] . Cancer Manag Res ， 2023 ， 15 ： 245 - 255 .

ZHANG G F ， QIN Y M ， LIU S B ， et al . Bibliometric analysis of research trends and topic areas in traditional Chinese medicine therapy for lymphoma [J ] . Pharm Biol ， 2024 ， 62 （ 1 ）： 13 - 21 .

王洪绪 . 外科证治全生集 [M ] . 北京：人民卫生出版社， 1989 ： 36 .

国家药典委员会 . 中华人民共和国药典：一部 [M ] . 2020年版 . 北京：中国医药科技出版社， 2020 ： 876 - 877 .

GUO Q J ， LIN J Y ， LIU R ， et al . Review on the applications and molecular mechanisms of Xihuang pill in tumor treatment [J ] . Evid Based Complement Alternat Med ， 2015 ， 2015 ： 854307 .

CAO B ， WANG S Y ， LI R S ， et al . Xihuang pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway [J ] . Biomed Pharmacother ， 2022 ， 151 ： 113081 .

CHEN C ， YUAN S M ， CHEN X H ， et al . Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway [J ] . Am J Cancer Res ， 2023 ， 13 （ 4 ）： 1347 - 1362 .

CHEN Z H ， LI Z M ， YANG S ， et al . The prospect of Xihuang pill in the treatment of cancers [J ] . Heliyon ， 2023 ， 9 （ 4 ）： e15490 .

MAO D ， FENG L ， HUANG S Q ， et al . Meta-analysis of Xihuang pill efficacy when combined with chemotherapy for treatment of breast cancer [J ] . Evid Based Complement Alternat Med ， 2019 ， 2019 ： 3502460 .

董旭辉 . 西黄丸联合CHOP方案治疗B细胞非霍奇金淋巴瘤临床疗效 [J ] . 中医药临床杂志， 2018 ， 30 （ 8 ）： 1492 - 1494 .

王钧 . 西黄丸联合CHOP方案治疗非霍奇金淋巴瘤的效果探析 [J ] . 当代医药论丛， 2019 ， 17 （ 9 ）： 175 - 176 .

ZHAO L ， ZHANG H ， LI N ， et al . Network pharmacology，a promising approach to reveal the pharmacology mechanism of Chinese medicine formula [J ] . J Ethnopharmacol ， 2023 ， 309 ： 116306 .

WU X D ， XU L Y ， LI E M ， et al . Application of molecular dynamics simulation in biomedicine [J ] . Chem Biol Drug Des ， 2022 ， 99 （ 5 ）： 789 - 800 .

RU J L ， LI P ， WANG J N ， et al . TCMSP：a database of systems pharmacology for drug discovery from herbal medicines [J ] . J Cheminform ， 2014 ， 6 ： 13 .

WANG H ， DU Y Y ， JI J ， et al . Utilizing network toxico-logy and molecular dynamics simulations to efficiently evaluate the neurotoxicity and underlying mechanisms of the endocrine-disrupting chemical triclosan [J ] . Int J Mol Sci ， 2025 ， 26 （ 19 ）： 9458 .

WANG Y ， WANG W H ， LIU K L ， et al . The mechanism of Xihuang pills’ intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway [J ] . J Ethnopharmacol ， 2024 ， 331 ： 118278 .

吴若霞，陈锦东，李松辉，等 . 西黄丸抗肿瘤作用机制的研究进展 [J ] . 湖南中医杂志， 2021 ， 37 （ 12 ）： 190 - 192 .

EL HAMEED EBID O A ， EZZ EL ARAB L R ， SAAD A S ， et al . Prognostic impact of MYD88 and TP53 mutations in diffuse large B Cell lymphoma [J ] . Ann Hematol ， 2023 ， 102 （ 12 ）： 3477 - 3488 .

WANG P H ， MA Y ， RAO X H ， et al . Kaempferol targets Src to exert its chemopreventive effects on mammary tumorigenesis via regulation of the PI3K/AKT pathway [J ] . Phytomedicine ， 2025 ， 141 ： 156701 .

PEIRÓ G ， ORTIZ-MARTÍNEZ F ， GALLARDO A ， et al . Src，a potential target for overcoming trastuzumab resistance in HER2-positive breast carcinoma [J ] . Br J Cancer ， 2014 ， 111 （ 4 ）： 689 - 695 .

LANTERMANS H C ， MINDERMAN M ， KUIL A ， et al . Identification of the SRC-family tyrosine kinase HCK as a therapeutic target in mantle cell lymphoma [J ] . Leukemia ， 2021 ， 35 （ 3 ）： 881 - 886 .

ZHANG N N ， ZHANG G ， LIU N ， et al . A novel orally available Syk/Src/Jak2 inhibitor，SKLB-850，showed potent anti-tumor activities in B cell lymphoma（BCL）mo-dels [J ] . Oncotarget ， 2017 ， 8 （ 67 ）： 111495 - 111507 .

CHEN J F ， GE X W ， ZHANG W ， et al . PI3K/AKT inhibition reverses R-CHOP resistance by destabilizing SOX2 in diffuse large B cell lymphoma [J ] . Theranostics ， 2020 ， 10 （ 7 ）： 3151 - 3163 .

SADAQAT M ， QASIM M ， TAHIR UL QAMAR M ， et al . Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining，molecular modeling，and microarray data analysis [J ] . Comput Biol Med ， 2023 ， 161 ： 107059 .

SULEMAN M ， YOUSAFI Q ， ALI J ， et al . Bioinformatics analysis of the differences in the binding profile of the wild-type and mutants of the SARS-CoV-2 spike protein variants with the ACE2 receptor [J ] . Comput Biol Med ， 2021 ， 138 ： 104936 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Study on the anti-hepatitis mechanism of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. and Abrus pulchellus subsp. mollis （Hance） Verdc. based on serum pharmacochemistry and network pharmacology

Mechanism prediction and validation of Kaixinsan in ameliorating neuroinflammation in Alzheimer’s disease

Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease

Material basis and mechanism of Kazakh classic prescription Wuzdekh in the treatment of enteritis

Study on the effects and mechanism of luteolin on osteogenic repair of bone defects

Related Author

FAN Lanlan

ZHANG Zijia

WANG Zhengtao

CHEN Wenya

LI Li

HUANG Mingjuan

WANG Xue

ZHOU Qiaowen

Related Institution

College of Pharmacy， Guangxi University of Chinese Medicine

Shanghai Key Laboratory of Compound Chinese Medicines， Institute of Chinese Materia Medica， Shanghai University of Traditional Chinese Medicine

School of Pharmacy， Guizhou University of Traditional Chinese Medicine

Preparation Department， the Affiliated Hospital of Traditional Chinese Medicine， Guangzhou Medical University

Geriatric Medicine Institute， Shenzhen Second People’s Hospital

⁰