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

doi:10.16139/j.1007-9610.2025.03.11

Abstract

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

CLC Number:

R735.9

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.

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Name	Average shortest path length	Betweenness centrality	Closeness centrality	Degree
Genistein	1.547 008 55	0.255 887	0.646 409	83
Kaempferol	2.111 111 11	0.087 602	0.473 684	50
Rutin	2.794 871 79	0.004 041	0.357 798	10
Glucuronic acid	2.846 153 85	0.001 373	0.351 351	7

Cluster	Nodes	Edges	Node IDs
1	53	1 137	SIRT1, INS, CDKN1A, PPARG, BCL2, PTGS2, CXCL1,MAPK8, CDK1, PPARA, TNF, GSK3B,STAT3, MMP9, PTEN, JUN, AKT1, ESR1, STAT1, RELA, FN1, CASP9, NOS2, AR, PGR, MMP1, CASP3, CXCL8, FOS, VCAM1, ATM, EGFR, ERBB2, TP53, CDK2, ICAM1, IL1B, MAPK3, MDM2, CCNB1, CCNA2, MAPK14, IGF1R, IFNG, CCL2, MPO, HIF1A, IKBKB, TGFB1, TIMP1, CDKN2A, HMOX1, MAPK1
2	5	9	NR1I2, GSTM1, UGT1A1, CYP1A2, CYP1B1
3	5	6	SOD1, SLC2A4, PPARGC1A, HMGCR, SOD2

Protein and PDB ID	Genistein	Glucuronic acid	Kaempferol	Rutin
MAPK8（3ELJ）	-8.5	-5.3	-8.2	-7.9
UTG1A1（AF-P22309-F1）	-8.2	-5.6	-8.3	-9.8
SOD2（1PL4）	-7.5	-5.1	-7.9	-8.2