Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity

Toxicol Mech Methods. 2023 Jan;33(1):38-46. doi: 10.1080/15376516.2022.2069531. Epub 2022 May 15.

Abstract

This study investigated the pharmacological mechanism of kaempferol in the treatment of oxaliplatin-induced neuropathic pain by network pharmacological method and cells experiment. The kaempferol and disease target genes were obtained from several databases, including TCMSP, SwissTargetPrediction, GeneCards, and CTD. Then, the common target genes of drugs and diseases were obtained using Venny online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were carried out to obtain the enriched molecular pathways associated with the kaempferol and disease. Finally, we constructed a neuropathic pain cell experiment to confirm the findings. 138 intersection targets were identified between targets of kaempferol and oxaliplatin-induced neurotoxicity. Enrichment analyses revealed that the IL-17 signaling pathway was associated with the therapeutic effects of kaempferol. Kaempferol down-regulated the mRNA expression levels of TNF-α, IL-6, and CCL2 in oxaliplatin-treated astrocytes. Our findings showed that kaempferol alleviated oxaliplatin-induced neurotoxicity via regulation of inflammation-related genes.

Keywords: Oxaliplatin; colorectal cancer; kaempferol; network pharmacology; neuropathic pain.

MeSH terms

  • Astrocytes
  • Databases, Factual
  • Drugs, Chinese Herbal*
  • Humans
  • Kaempferols / pharmacology
  • Molecular Docking Simulation
  • Neuralgia*
  • Neurotoxicity Syndromes* / drug therapy
  • Neurotoxicity Syndromes* / etiology
  • Neurotoxicity Syndromes* / prevention & control
  • Oxaliplatin / toxicity

Substances

  • Kaempferols
  • Oxaliplatin
  • Drugs, Chinese Herbal