Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection

Abstract

Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI’s role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1β, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

“…In the vascular endothelium, DHI attenuates lipopolysaccharides (LPS) and oxidized LDL (oxLDL) induced secretion of tumor necrosis factor-α (TNF-α), interleukin 1 β (IL-1β), and interleukin 10 (IL-10), by inhibiting the activation of p38, nuclear factor-kappa B (NF-κB), and c-jun. This may be a potential mechanism for DHI to protect against stroke and coronary heart disease [10]. DHI attenuates hypoxic damage in brain microvascular endothelial cells.…”

“…DHI is a composite formula of two eminent Chinese herbal medicine-Salviae Miltiorrhizae (Dan Shen) and Flos Carthami (Hong Hua). Compared with single-target western medicine, DHI is a multi-component and multi-target medicinal preparation, which indicates that DHI may have a wider range of clinical applications [10,86,106].…”

“…Alternative and complementary therapies have played a major role in the management and treatment of cardiovascular and cerebrovascular diseases. Danhong Injection (DHI) is widely used in China due to its safety and efficacy in treating cardiovascular and cerebrovascular diseases [10][11][12][13]. Therefore, DHI could be exploited as an important complementary drug preparation for pharmacotherapy of cardiovascular and cerebrovascular diseases.…”

Application of Traditional Chinese Medicines in Postoperative Abdominal Adhesion

“…Wu et al [83] have reported that treatment with DHI for 7 days alleviates the formation of abdominal adhesion by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model. DHI has been extensively used in clinical practices for a long time, which supported to serve as a promising drug to prevent PAA [84].…”

Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology

“…DAVID provides high-throughput functional annotation bioinformatics to perform functional annotation and enrichment analysis. e cutoff of recognized GO terms is set to FDR < 0.01 and KEGG pathways is set to P value <0.05 [26,27].…”