Herbal Formula Modified Bu-Shen-Huo-Xue Decoction Attenuates Intervertebral Disc Degeneration via Regulating Inflammation and Oxidative Stress

Abstract

Objective. This study aims to clarify the potential mechanism of modified Bu-Shen-Huo-Xue decoction (MBSHXD) in treating intervertebral disc degeneration (IDD) with methods of network pharmacology and molecular docking. Methods. An MBSHXD and IDD-related common target gene set was established through TCMSP, UniProt, and two disease gene databases. GO and KEGG enrichment analysis and protein-protein interaction (PPI) networks were performed through the R platform and STRING to discover the potential mechanism. Molecular docking between the active ingredients and the core genes is used to calculate the binding energy. Results. A total of 147 active ingredients and 79 common genes (including 10 core genes, TNF, VEGFA, IL6, MAPK3, AKT1, MAPK8, TP53, JUN, MMP9, and CXCL8) were identified. The results of GO and KEGG enrichment analysis showed that MBSHXD plays an essential role in regulating inflammation and oxidative stress. The meaningful pathways are the AGE-RAGE signaling pathway in diabetic complications, the IL-17 signaling pathway, the TNF signaling pathway, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and apoptosis. In addition, the PPI network and molecular docking further demonstrated the roles that nine bioactive ingredients of MBSHXD play in IDD treatment through their interference with core target proteins. Conclusion. This study reveals that MBSHXD has the characteristics of a “multi-component, multi-target, and multi-pathway” in the treatment of IDD by regulating inflammation and oxidative stress, and network pharmacology may provide a feasible method to verify the molecular mechanism of MBSHXD for IDD by combining with molecular docking.

Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration

“…Oxidative stress and inflammatory responses mediated by the AGE/RAGE signalling pathway are important in IDD progression. 52 Illien-Jünger et al 53 suggested that activation of the AGE/RAGE pathway induces hypertrophy and osteogenic differentiation of IVD cells. More importantly, the accumulation of AGEs caused changes in the oxidative microenvironment of nucleus pulposus tissues, which in turn led to IDD.…”

Identification of the active compounds and their mechanisms of medicinal and edible Heigen based on UHPLC-Q-Exactive Orbitrap MS and network pharmacology

“…Targets related to bioactive ingredients in Heigen were based on the analysis of the components in the serum of rats that were administered Heigen exacted, and the SDF files were downloaded from the PubChem database (Lin at al., 2022). Using Swiss Target Prediction to get an accurate prediction of the potential targets.…”

“…These main active ingredients are related to the following genes: AKT1, PTGS2, MMP9, EGFR, CASP3, PPARG, TLR4, ESR1, CCND1, and MAPK8, the molecular docking results shown in Table 4. The compound structures download from PubChem (Lin at al., 2022). The main results are visualized by Pymol as shown in Figure 7, these docking results indicate that these active components were bound to the target protein's active site.…”

“…UHPLC-Q-Exactive Orbitrap MS is an efficiency and sensitivity technique to detect and identify chemical components or biological sample (Li et al, 2020), it can rapidly identify known metabolites by ccomparing experimental spectral data with databases (Ghane et al, 2022). Network pharmacology is an emerging research approach combined with pharmacology, bioinformatics, and network biology (Lin et al, 2022). The compound-target-pathway networks can be predicted the biologically active ingredients and elaborate the compound mechanism of action (Wang et al, 2021).…”