Journal of Surgery Concepts & Practice >

2025 , Vol. 30 >Issue 03: 247 - 255

DOI: https://doi.org/10.16139/j.1007-9610.2025.03.11

Original article

Investigation of the mechanism of Huaier (Vanderbylia robiniophila) anti-pancreatic cancer based on network pharmacology, molecular docking, and two-sample Mendelian randomization analysis

  • JIN Jiabin ,
  • MA Junjun ,
  • YE Feng ,
  • MA Shiyu ,
  • CHEN Jingxian
Expand
  • a. Department of General Surgery, b. Department of Pharmacy, c. Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2024-12-20

  Online published: 2025-09-01

Fold

Abstract

Objective To explore the mechanism of action of Huaier (Vanderbylia robiniophila) against pancreatic cancer. Methods The chemical components and targets of Huaier (Vanderbylia robiniophila) were searched through the Herb database. Pancreatic cancer-related targets were screened from GeneCards, NCBI, and DisGeNET online databases, and a Venn diagram was drawn to obtain the intersection targets of drugs and diseases. The protein-protein interaction (PPI) network was constructed using the String platform, and a series of network diagrams were drawn using Cytoscape 3.8.0 software to screen core targets and perform GO analysis and KEGG pathway enrichment analysis on the target genes. Finally, the key active components were molecularly docked with potential target genes using AutoDock software. The KEGG enrichment top 20 pathways and the whole-genome association analysis data of pancreatic cancer were used to further validate the results using the Open GWAS database through Mendelian randomization analysis. Results A total of 4 effective components of Huaier (Vanderbylia robiniophila) were identified, 112 drug-disease intersection targets, the main active components were kaempferol, rutin, genistein, and glucuronic acid, and the core targets were mitogen-activated protein kinase 8 (MAPK8), uridine diphosphate(UDP)-glucuronic acid transferase 1 family peptide A1 (UGT1A1), and superoxide dismutase 2 (SOD2). The mechanism of action may be related to pancreatic cancer, tumor necrosis factor(TNF) signaling pathway, and interleukin(IL)-17 signaling pathway. The molecular docking showed that the main active components had good docking activity with the key targets. After screening, 73 genes were retained, and 24,195,229 single nucleotide polymorphism(SNP) were used for two-sample Mendelian randomization analysis. The analysis results showed that MAPK8 may be an important therapeutic target for pancreatic cancer. Conclusions Huaier (Vanderbylia robiniophila) may exert an anti-pancreatic cancer effect by acting on MAPK8, providing initial theoretical evidence for further verifying the mechanism of action of Huaier in treating pancreatic cancer.

Key words： Huaier (Vanderbylia robiniophila); Pancreatic cancer; Network pharmacology; Molecular docking; Mendelian randomization analysis

Cite this article

JIN Jiabin , MA Junjun , YE Feng , MA Shiyu , CHEN Jingxian . Investigation of the mechanism of Huaier (Vanderbylia robiniophila) anti-pancreatic cancer based on network pharmacology, molecular docking, and two-sample Mendelian randomization analysis[J]. Journal of Surgery Concepts & Practice, 2025 , 30(03) : 247 -255 . DOI: 10.16139/j.1007-9610.2025.03.11

References

[1] RYAN D P, HONG T S, BARDEESY N. Pancreatic adenocarcinoma[J]. N Engl J Med, 2014, 371(11):1039-1049.
[2] KIM H, PARK S Y, PARK Y, et al. Assessment of learning curve and oncologic feasibility of robotic pancreaticoduodenectomy: a propensity score-based comparison with open approach[J]. J Hepatobiliary Pancreat Sci, 2022, 29(6):649-658.
[3] NAFFOUJE S A, POINTER D T Jr, SATYADI M A, et al. Surgical approach to pancreaticoduodenectomy for pancreatic adenocarcinoma:uncomplicated ends justify the means[J]. Surg Endosc, 2022, 36(7):4912-4922.
[4] 胡志强, 游伟程, 潘凯枫, 等. 中、美两国癌症流行特征分析——《2023美国癌症统计报告》解读[J]. 科技导报, 2023, 41(18):18-28.
  HU Z Q, YOU W C, PAN K F, et al. Epidemiological characteristics of cancers in China and America: interpretation of the report of American cancer statistics,2023[J]. Sci Technol Rev, 2023, 41(18):18-28.
[5] 雷蕾, 高彦茹, 蔡洲, 等. 槐耳多糖通过抑制AKT/GSK3β/Snail信号通路抑制胰腺癌细胞增殖和上皮间质转化[J]. 现代肿瘤医学, 2023, 31(24):4536-4541.
  LEI L, GAO Y R, CAI Z, et al. Huaier polysaccharide inhibits proliferation and epithelial-mesenchymal transition of pancreatic cancer cells by inhibiting AKT/GSK3β/Snail signaling pathway[J]. J Mod Oncol, 2023, 31(24):4536-4541.
[6] FANG S, DONG L, LIU L, et al. HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine[J]. Nucleic acids res, 2021, 49(D1):D1197-D1206.
[7] LOURENCO M V, FROZZA R L, DE FREITAS G B, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models[J]. Nat Med, 2019, 25(1):165-175.
[8] SAFRAN M, DALAH I, ALEXANDER J, et al. Gene-cards version 3: the human gene integrator[J]. Database(Oxford), 2010,2010:baq020.
[9] NCBI Resource Coordinators. Database resources of the national center for biotechnology information[J]. Nucleic Acids Res, 2018, 46(D1):D8-D13.
[10] PI?ERO J, BRAVO à, QUERALT-ROSINACH N, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants[J]. Nucleic acids research, 2017, 45(D1):D833-D839.
[11] SZKLARCZYK D, GABLE A L, LYON D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic acids research, 2019, 47(D1):D607-D613.
[12] DONCHEVA N T, MORRIS J H, GORODKIN J, et al. Cytoscape StringApp: network analysis and visualization of proteomics data[J]. J Proteome Res, 2019, 18(2):623-632.
[13] SUN C, YUAN Q, WU D, et al. Identification of core genes and outcome in gastric cancer using bioinformatics analysis[J]. Oncotarget, 2017, 8(41):70271-70280.
[14] 邓叔群. 中国的真菌[M]. 北京: 北京科技出版社,1963:515.
  DENG S Q. Fungi of China[M]. Beijing: Beijing Science and Technology Press,1963:515.
[15] 潘超, 郑吴彬, 付凯, 等. 槐耳清膏对胰腺癌细胞增殖和迁移的影响[J]. 江苏医药, 2019, 45(9):865-870,封2.
  PAN C, ZHENG W B, FU K, et al. Effects of Huaier cream on proliferation and migration of panereatie cancer cells[J]. Jiangsu Med J, 2019, 45(9):865-870,cover 2.
[16] 宋志远, 张晖, 孔棣. 槐耳颗粒对人胰腺癌细胞Panc-2原位移植模型的干预研究[J]. 吉林医学, 2019, 40(1):3-6.
  SONG Z Y, ZHANG H, KONG D. Interventional researches of Huai' er granula on human pancreatic carcinomas Mini-Panc-2 model[J]. Jilin Med, 2019, 40(1):3-6.
[17] LIN R, BAO X, WANG H, et al. TRPM2 promotes pancreatic cancer by PKC/MAPK pathway[J]. Cell Death Dis, 2021, 12(6):585.
[18] IMRAN M, SALEHI B, SHARIFI-RAD J, et al. Kaempferol: a key emphasis to its anticancer potential[J]. Mo-lecules, 2019, 24(12):2277.
[19] LEE J, KIM J H. Kaempferol inhibits pancreatic cancer cell growth and migration through the blockade of EGFR-related pathway in vitro[J]. PLoS One, 2016, 13:11(5):e0155264.
[20] WANG Y, DONG B, XUE W, et al. Anticancer effect of radix astragali on cholangiocarcinoma in vitro and its mechanism via network pharmacology[J]. Med Sci Monit, 2020,26:e921162.
[21] 陈素贤, 谷泽慧, 马炀斐, 等. 芦丁对人结肠癌SW480细胞凋亡的促进作用及其作用机制[J]. 吉林大学学报(医学版), 2022, 48(2):356-363.
  CHEN S X, GU Z H, MA Y F, et al. Promotion effect of rutin on apoptosis of human colon cancer SW480 cells and its mechanism[J]. J Jilin Univ (Med Ed), 2022, 48(2):356-363.
[22] 万英凤, 王玲兰, 许佑君, 等. 染料木素在乳腺癌MCF-7细胞内的代谢研究[J]. 沈阳药科大学学报, 2010, 27(10):813-820.
  WAN Y F, WANG L L, XU Y J, et al. Metabolism study of genistein in breast cancer MCF-7 cells[J]. J Shenyang Pharmaceutical Univ, 2010, 27(10):813-820.
[23] 程雨晴. 茵栀黄中药成分葡萄糖醛酸代谢筛选及其细胞毒性效应[D]. 湖南: 湖南师范大学, 2017.
  CHENG Y Q. Glucuronic acid metabolism screening of Yinzhihuang traditional Chinese medicine component and its cytotoxic effects[D]. Hunan: Hunan Normal University, 2017.
[24] 卢意, 蔡海波, 谭文松. 甘露糖和葡萄糖醛酸组合促进CIK细胞体外扩增[J]. 中国免疫学杂志, 2019, 35(15):1865-1870.
  LU Y, CAI H B, TAN W S. Mannose and glucuronic acid combination promotes in vitro expansion of CIK cells[J]. Chin J Immunol, 2019, 35(15):1865-1870.
[25] SAHU N, CHAN E, CHU F, et al. Cotargeting of MEK and PDGFR/STAT3 pathways to treat pancreatic ductal adenocarcinoma[J]. Mol Cancer Ther, 2017, 16(9):1729-1738.
[26] BIRNEY E. Mendelian randomization[J]. Cold Spring Harb Perspect Med, 2022, 12(4):a041302.
[27] 郭强, 黄兴, 夏宁, 等. 全球及中国胰腺癌的流行病学现状及趋势[J]. 中国普外基础与临床杂志, 2025, 32(6):677-686.
  GUO Q, HUANG X, XIA N, et al. Epidemiological status and trends of pancreatic cancer globally and in China[J]. Chin J Bases Clin Gen Surg, 2025, 32(6):677-686.
[28] 陈东宇, 杨晓雨, 樊文龙, 等. 1990-2019年亚洲主要国家胰腺癌疾病负担和归因风险因素及相关预测分析[J]. 中华肿瘤杂志, 2022, 44(9):955-961.
  CHEN D Y, YANG X Y, FAN W L, et al. Disease burden and attributable risk factors of pancreatic cancer and related predictive analysis in major Asian countries from 1990 to 2019[J]. Chin J Oncol, 2022, 44(9):955-961.
[29] 王运玉, 吴柱国. 槐耳抗肿瘤的机制及临床应用[J]. 广东医学院学报, 2007, 25(1):77-79.
  WANG Y Y, WU Z G. Mechanism and clinical application of huaier in tumor treatment[J]. J Guangdong Med Coll, 2007, 25(1):77-79.
Options
Outlines

/

〈 〉