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

Chun Li,Jie Zhou,Wen Bing Zhi,Qi-Qi Liu,Xia Du,Yang Liu,Hong Zhang,Ye Li,Chun Liu Wang

doi:10.1155/2020/5196302

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.

Highlights

Cardiocerebral vascular diseases (CCVDs), including thrombosis, atherosclerosis, hypertension, cardiac hypertrophy, myocardial infarction, heart failure, stroke, and cerebral ischemia, are the major health problem all over the world, claiming more than 17.3 million lives annually [1,2,3]
It is potently demonstrated that the same active ingredients can act on different targets, and different active constituents can act on the same target, reflecting its multicomponent, multitarget anti-CCVD mode of action. en, through the OMIM and pharmGKB databases, 158 targets obtained were mapped to stroke-related drug targets, 547 targets obtained were reflected to antiplatelet aggregation-related drug targets, 232 targets obtained were mirrored to antiatherosclerosis-related drug targets, 479 targets obtained were reflected to improve microcirculation-related drug targets, and 79 targets obtained were mirrored to antithrombinrelated drug targets
We found the complement and coagulation cascades pathway (DC 7, cell component (CC) 0.2381, betweenness centrality (BC) 0.5017) and PI3K-Akt signaling pathway (DC 6, CC 0.2518, BC 0.5513) showed higher centrality in the target-pathway network

Summary

Introduction

Cardiocerebral vascular diseases (CCVDs), including thrombosis, atherosclerosis, hypertension, cardiac hypertrophy, myocardial infarction, heart failure, stroke, and cerebral ischemia, are the major health problem all over the world, claiming more than 17.3 million lives annually [1,2,3]. Given the high incidence and high mortality of CCVDs, seeking feasible prevention and treatment strategy is highly imperative and critical to human health [4, 5]. Western medicine is currently the mainstream medical treatment for CCVDs. some certainly existing ill-effects are still unavoidable. Erefore, it is very indispensable to seek better, safe, and effective treatment strategies in treatment of CCVDs. Herb pairs, the simplest form and the centralized representative of Chinese herbal compatibility, intrinsically convey the basic idea of traditional Chinese medicines’ prescriptions that has attracted comprehensive attention Some antihypertensive drugs have triggered serious side effects, with hot flush, fatigue, shortness of breath, headache, dizziness rhabdomyolysis, and hepatic diseases [6,7,8]. erefore, it is very indispensable to seek better, safe, and effective treatment strategies in treatment of CCVDs.

Methods

Discussion

Conclusion