A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui‐Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases

Abstract

Cardiocerebral vascular diseases (CCVDs) are the main reasons for high morbidity and mortality all over the world, including atherosclerosis, hypertension, myocardial infarction, stroke, and so on. Chinese herbs pair of the Cinnamomum cassia Presl (Chinese name, rougui) and the Aconitum carmichaelii Debx (Chinese name, fuzi) can be effective in CCVDs, which is recorded in the ancient classic book Shennong Bencao Jing, Mingyibielu and Thousand Golden Prescriptions. However, the active ingredients and the molecular mechanisms of rougui-fuzi in treatment of CCVDs are still unclear. This study was designed to apply a system pharmacology approach to reveal the molecular mechanisms of the rougui-fuzi anti-CCVDs. The 163 candidate compounds were retrieved from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). And 84 potential active compounds and the corresponding 42 targets were obtained from systematic model. The underlying mechanisms of the therapeutic effect for rougui-fuzi were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, component-target-disease (C-T-D) and target-pathway (T-P) networks were constructed to further dissect the core pathways, potential targets, and active compounds in treatment of CCVDs for rougui-fuzi. We also constituted protein-protein in interaction (PPI) network by the reflect target protein of the crucial pathways against CCVDs. As a result, 21 key compounds, 8 key targets, and 3 key pathways were obtained for rougui-fuzi. Afterwards, molecular docking was performed to validate the reliability of the interactions between some compounds and their corresponding targets. Finally, UPLC-Q-Exactive-MSE and GC-MS/MS were analyzed to detect the active ingredients of rougui-fuzi. Our results may provide a new approach to clarify the molecular mechanisms of Chinese herb pair in treatment with CCVDs at a systematic level.

Decoding the Mechanism of Huanglian Jiedu Decoction in Treating Pneumonia Based on Network Pharmacology and Molecular Docking

“…The lower the binding energy, the more stable the binding conformation of the receptor and the ligand. The binding energy −5.0 kcal/mol is set as the threshold to determine whether the binding of the receptors and ligands is good or not ( Li et al, 2020 ). Therefore, we screened out the ligand which binds the best (with the lowest energy) to the receptor based on the binding energy.…”

A Song of Ice and Fire: Cold and Hot Properties of Traditional Chinese Medicines

“…Fuzi, the processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), is an herb extensively used in TCM to treat the diseases with cold symptoms because of its hot property, which was originally recorded in Shennong Bencao Jing ( Zheng et al, 2014 ; Li C. et al, 2020 ) . In Bencao Jingdu , it was viewed as the key TCM to ameliorate Yang deficiency and rescue the patient from prostration ( Zhou et al, 2015 ).…”

“…For example, both Fuzi and Rougui are hot TCMs; however, they cannot be used interchangeably in the clinic in most cases. A previous study based on network pharmacology to explore the mechanism of Fuzi and Rougui in the treatment of cardiocerebral vascular diseases showed that, among the 194 targets of Fuzi and Rougui, 45 targets are shared; that is, three-quarters of the targets are different ( Li C. et al, 2020 ). In addition, from a metabolic perspective, Fuzi can promote energy metabolism by increasing the activity of Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase enzymes in hepatocytes, which is closely related to thermogenesis ( Yu et al, 2012 ).…”

A Review of the Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicology of Corydalis yanhusuo

“…Network pharmacology explains the therapeutic effect of herb pairs. 104 We cross-referenced the chemical compositions of C. yanhusuo with the pharmacological functions mentioned in the Chinese Medicine System Pharmacology Database. Using the systems pharmacology analysis platform TCMSP (http:// bigd.…”