Mechanism of Rhizoma Chuanxiong for the treatment of diabetic kidney disease based on network pharmacology

Abstract

Background: Although Rhizoma Chuanxiong has been used for the treatment of diabetic kidney disease (DKD), the relevant mechanisms remain unclear. The purpose of this study was to investigate the potential targets and mechanisms of Rhizoma Chuanxiong in treating DKD, utilizing network pharmacology.

Methods: Active compounds of Rhizoma Chuanxiong were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform database. SwissTargetPrediction was used to obtain the potential targets of active ingredients. DKD-associated targets were gathered from the GeneCards, DisGeNET, and OMIM databases. The STRING database and Cytoscape 3.7.2 were used for investigating core targets and interactions among targets. Gene Ontology and Kyoto Encyclopedia of Gene Genomes enrichment were performed using DAVID database. Molecular docking was performed using AutoDock-1.5.7 based on the crystal structures of the targets as deposited in the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank.

Results: The top 10 core targets were identified, namely PPARG, AKT1, EGFR, STAT3, CASP3, PPARA, ICAM1, PTGS2, SRC, and MMP9. Enrichment analysis revealed that the primary pathways involving these targets including prolactin signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, VEGF signaling pathway, and FoxO signaling pathway. Molecular docking demonstrated that mandenol exhibited a strong binding affinity toward EGFR domain, and wallichilide displayed pronounced binding affinity toward AKT1, EGFR, STAT3, and PTGS2 domains. Additionally, myricanone and senkyunone also showed strong binding affinity for AKT1, EGFR, CASP3, STAT3, and PTGS2 domains.

Conclusions: This study revealed the potential multi-component and multi-target mechanisms of Rhizoma Chuanxiong in treating DKD through network pharmacology. Supplementary experiments are required to further verify these findings.

Keywords: DKD; Rhizoma Chuanxiong; mechanism; network pharmacology.

Figure 1.

The overlapping targets between Rhizoma Chuanxiong and DKD.

Figure 2.

PPI network of overlapping targets.

Figure 3.

Screening and visualization of core targets.

Figure 4.

(a–c) GO (BP, MF, CC) analyses the therapeutic target genes of Rhizoma Chuanxiong for treatment of DKD.

Figure 5.

KEGG enrichment analysis of the Rhizoma Chuanxiong for the treatment of DKD.

Figure 6.

Relationships between KEGG pathways and active compounds, targets of Rhizoma Chuanxiong for the treatment of DKD.

Figure 7.

Molecular docking between active ingredients and key targets. (a) Mandenol with AKT1 (PDB code: 4GV1); (b) Mandenol with EGFR (PDB code: 4RJ3); (c) Mandenol with CASP3 (PDB code: 5IAE); (d) Mandenol with STAT3 (PDB code: 6QHD); (e) Mandenol with PTGS2 (PDB code: 5F1A); (f) Myricanone with AKT1 (PDB code: 4GV1); (g) Myricanone with EGFR (PDB code: 2RGP); (h) Myricanone with CASP3 (PDB code: 3PD1); (i) Myricanone with STAT3 (PDB code: 6TLC); (j) Myricanone with PTGS2 (PDB code: 5IKV); (k) Senkyunone with AKT1 (PDB code: 3QKL); (l) Senkyunone with EGFR (PDB code: 3IN8); (m) Senkyunone with CASP3 (PDB code: 4EHL); (n) Senkyunone with STAT3 (PDB code: 6QHD); (o) Senkyunone with PTGS2 (PDB code: 5IKR); (p) Wallichilide with AKT1 (PDB code: 7NH5); (q) Wallichilide with EGFR (PDB code: 3WA4); (r) Wallichilide with CASP3 (PDB code: 5IAB); (s) Wallichilide with STAT3 (PDB code: 5AX3); (t) Wallichilide with PTGS2 (PDB code: 5IKR).