Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang–Qi–Gui–Zhi–Wu–Wu decoction against deep vein thrombosis

Abstract

Background Huangqi Guizhi Wuwu decoction (HQGZWWD) has been used to treat and prevent deep vein thrombosis (DVT) in China. However, its potential mechanisms of action remain unclear. This study aimed to utilize network pharmacology and molecular docking technology to elucidate the molecular mechanisms of action of HQGZWWD in DVT. Methods We identified the main chemical components of HQGZWWD by reviewing the literature and using a Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used GeneCards and Online Mendelian Inheritance in Man databases to identify the targets of DVT. Herb-disease-gene-target networks using Cytascape 3.8.2 software; a protein–protein interaction (PPI) network was constructed by combining drug and disease targets on the STRING platform. Additionally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking verification of active components and core protein targets was conducted. Results A total of 64 potential targets related to DVT were identified in HQGZWWD, with 41 active components; quercetin, kaempferol, and beta-sitosterol were the most effective compounds. The PPI network analysis revealed that AKT1, IL1B, and IL6 were the most abundant proteins with the highest degree. GO analysis indicated that DVT treatment with HQGZWWD could involve the response to inorganic substances, positive regulation of phosphorylation, plasma membrane protein complexes, and signaling receptor regulator activity. KEGG analysis revealed that the signaling pathways included pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results indicated that quercetin, kaempferol, and beta-sitosterol exhibited strong binding affinities for AKT1, IL1B, and IL6. Conclusion Our study suggests that AKT1, IL1B, and IL6 are promising targets for treating DVT with HQGZWWD. The active components of HQGZWWD likely responsible for its effectiveness against DVT are quercetin, kaempferol, and beta-sitosterol, they may inhibit platelet activation and endothelial cell apoptosis by regulating the PI3K/Akt and MAPK signaling pathways, slowing the progression of DVT.

Exploring the potential mechanism and molecular targets of Taohong Siwu Decoction against deep vein thrombosis based on network pharmacology and analysis docking

“…We have previously conducted network pharmacology studies on the treatment of deep vein thrombosis (DVT) using Chinese herbal medicine. [ 1 ] Surprisingly, our findings align with the results of this study. It is well-known that IL1B and IL6 are biologically active cytokines, [ 40 – 42 ] and their involvement in cellular inflammation has been linked to DVT occurrence.…”

“…[ 39 ] The 3 active ingredients, quercetin, beta-sitosterol, and kaempferol, are remarkably consistent with the effective ingredients of Huangqi Guizhi Wuwu Decoction that we previously researched for treating DVT. [ 1 ] This strengthens our belief in the crucial role these ingredients play in traditional Chinese medicine’s treatment of DVT and boosts our confidence for future experimental research.…”

“…This can block or narrow the vein, leading to serious complications. [ 1 , 2 ] DVT is highly prevalent, with studies showing that patients with femoral fractures have a preoperative incidence rate of 26.4% even with anticoagulants and physical prevention measures, [ 3 ] while those undergoing major orthopedic surgery have an incidence rate of 40% to 60%. [ 4 ] The danger of DVT lies in its potential to cause fatal pulmonary embolism when an embolus dislodges, resulting in high mortality rates and contributing significantly to perioperative and accidental hospital deaths.…”