Systematic Elaboration of the Pharmacological Targets and Potential Mechanisms of ZhiKe GanCao Decoction for Preventing and Delaying Intervertebral Disc Degeneration

Abstract

Background. ZhiKe GanCao Decoction (ZKGCD) is a commonly used traditional Chinese medicine in the clinical treatment of intervertebral disc degeneration (IDD). However, its active ingredients and mechanism of action remain unclear. This study aims to propose the systematic mechanism of ZKGCD action on IDD based on network pharmacology, molecular docking, and enrichment analysis. Methods. Firstly, the common target genes between ZKGCD and IDD were identified through relevant databases. Secondly, the protein-protein interaction (PPI) network of common genes was constructed and further analyzed to determine the core active ingredients and key genes. Thirdly, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of common genes were performed. Finally, the stability of the binding between core active ingredients and key genes was verified by molecular docking analysis. Results. “Intersecting genes-active components” network consists of 154 active ingredients and 133 common genes. The ten key genes are AKT1, TNF, IL6, TP53, IL1B, JUN, CASP3, STAT3, MMP9, and MAPK3. Meanwhile, quercetin (Mol000098), luteolin (Mol000006), and kaempferol (Mol000422) are the most important core active ingredients. The main signal pathways selected by KEGG enrichment analysis includes AGE-RAGE signaling pathway in diabetic complications (hsa04933), TNF signaling pathway (hsa04668), IL-17 signaling pathway (hsa04657), cellular senescence (hsa04218), apoptosis (hsa04210), and PI3K-Akt signaling pathway (hsa04151), which are mainly involved in inflammation, apoptosis, senescence, and autophagy. Conclusion. This study provides a basis for further elucidating the mechanism of action of ZKGCD in the treatment of IDD and offers a new perspective on the conversion of the active ingredient in ZKGCD into new drugs for treating IDD.

Network pharmacology approach to investigate the multitarget mechanisms of Zhishi Rhubarb Soup on acute cerebral infarction

“…Binding energy is considered to be one of the key indicators to verify the stability of the conformation of the bound protein and active ingredient (Sun et al. 2022 ). Therefore, we performed molecular docking analysis on the top 5 key target and the top 4 bioactive components, and the results are shown in Figure 5 .…”

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

“…Finally, kaempferol administration significantly relieved the IL-1β-stimulated increase in p38, JNK and ERK1/2 phosphorylation [ 56 ]. In favor of the IVD-protective role of kaempferol, the compound was found to be among the active ingredients of ZhiKe GanCao Decoction (ZKGCD)—a commonly used traditional Chinese medicine in the clinical treatment of IDD—based on network pharmacology, molecular docking and enrichment analysis [ 57 ].…”

Exploring the molecular mechanism of notoginsenoside R1 in sepsis-induced cardiomyopathy based on network pharmacology and experiments validation

“…In this study, molecular docking analysis was used to determine whether the key targets had good stability with the corresponding active ingredients. Binding energy is considered to be one of the key indicators to verify the stability of the conformation of the bound protein and active ingredient (Sun et al, 2022). Molecular docking of hub genes involved in the inflammatory pathway and cAMP pathway to NG-R1 was performed using Autodock Vina software by the comprehensive network pharmacology analysis described above.…”