Mechanism of modified danggui buxue decoction in glucocorticoid-induced osteoporosis: A discussion based on network pharmacology and molecular docking

Abstract

Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights.

Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs' therapeutic mechanisms.

Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1.

Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.

Keywords: Glucocorticoid-induced osteoporosis; Modified danggui buxue decoction; Molecular docking; Network pharmacology.

Fig. 1

Overview of the methodological framework for investigating the effects of Modified Danggui Buxue Decoction (DGBXD) on glucocorticoid-induced osteoporosis (GIOP). The schematic diagram outlines the step-by-step approach utilized in our study, including the identification of active compounds in DGBXD, prediction of target genes, network pharmacology analysis, and molecular docking studies.

Fig. 2

GIOP target and common target prediction. A–B, Venn diagrams for the GIOP-related targets (A) and the common targets of DGBXD-GIOP (B). DGBXD, Modified Danggui Buxue Decoction; GIOP, glucocorticoid-induced osteoporosis.

Fig. 3

Establishment of protein–protein interaction network. The edge represented the protein–protein interaction. The thickness of the edge indicated the intensity of the data support. All nodes were visualized with a degree value. Larger nodes with darker colors indicated higher degree values.

Fig. 4

Drug-active compound-disease-target network diagram. A, The top 10 key target genes; B, The Sankey diagram for the 10 main effective active compounds and 10 key target genes.

Fig. 5

GO and KEGG enrichment analyses. A, The results of the GO functional enrichment analysis. The ordinate included molecular functions (MFs), cell components (CCs), and biological processes (BPs), and the abscissa indicated the degree of enrichment. B, The results of the KEGG enrichment analysis. The ordinate included related diseases and involved pathways, and the abscissa meant the degree of enrichment. The size of each dot corresponds to the number of genes involved, with larger dots denoting a greater quantity of genes. The color gradient from blue to red reflects the increasing levels of enrichment significance, with red indicating the highest degree of enrichment. All displayed results represent findings with a p-value <0.05, emphasizing statistically significant enrichments.

Fig. 6

Molecular docking heat map of the 10 main active components and 10 target proteins of the Modified Danggui Buxue Decoction (DGBXD).

Fig. 7

Molecular docking results. (A) AKT1-luteolin; (B) AKT1-formononetin; (C) AKT1-beta-carotene; (D) AKT1-isorhamnetin; (E) ESR1-formononetin; (F) ESR1-isorhamnetin.