Exploring the Mechanism of Hawthorn Leaves Against Coronary Heart Disease Using Network Pharmacology and Molecular Docking

Abstract

Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.

Exploring the Mechanism of Arctium Lappa L. Leaves in the Treatment of Alzheimer's Disease Based on Chemical Profile, Network Pharmacology and Molecular Docking

“…Molecular Docking: A molecular docking method was performed as described previously with some modifications. [29] The 2D structures of compounds were provided by PubChem (https://pubchem.ncbi.nlm.nih. gov/).…”

“…A molecular docking method was performed as described previously with some modifications. [ 29 ] The 2D structures of compounds were provided by PubChem (https://pubchem.ncbi.nlm.nih.gov/). The Chem 3D software was used to convert the 2D structure into 3D and optimized the 3D structure with the minimum free energy.…”

Integrating UPLC-Q-Orbitrap MS with serum pharmacochemistry network and experimental verification to explore the pharmacological mechanisms of Cynanchi stauntonii rhizoma et radix against sepsis-induced acute lung injury

“…The potential targets of the main active ingredients of traditional Chinese medicine in mouse serum were identified using PharmMapper (http://www.lilab-ecust.cn/PharmMapper/). These ingredients were then used to search for target genes by utilizing 2D molecules downloaded from PubChem (Ding et al, 2022). The UniProt ID (https://www.uniprot.org/) was standardized with the gene symbol and duplicate Csrer targets were eliminated (Tian et al, 2020).…”