The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification

Yong Yuan; Huajiang Liu; Qingwen Meng

doi:10.31083/j.fbl2805094

The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification

Front Biosci (Landmark Ed). 2023 May 22;28(5):94. doi: 10.31083/j.fbl2805094.

Authors

Yong Yuan^{1

2}, Huajiang Liu³, Qingwen Meng^{4

5}

Affiliations

¹ College of Pediatrics, Hainan Medical University, 571199 Haikou, Hainan, China.
² Department of Traditional Chinese Medicine, The First Affiliated Hospital of Hainan Medical University, 570100 Haikou, Hainan, China.
³ Department of Interventional Vascular Surgery, The First Affiliated Hospital of Hainan Medical University, 570100 Haikou, Hainan, China.
⁴ Hainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan Medical University, 571199 Haikou, Hainan, China.
⁵ Department of Cardiovascular Medicine, The First Affiliated Hospital of Hainan Medical University, 570100 Haikou, Hainan, China.

PMID: 37258471
DOI: 10.31083/j.fbl2805094

Abstract

Background: Huang Qi (HQ, Astragalus) and Hong Hua (HH, Safflower), two Chinese herbal remedies, are widely used to treat coronary heart disease (CHD). However, the underlying mechanisms of this herb pair remain unclear. The aim of this study was to determine the potential synergistic effects and mechanisms of Astragalus-Safflower in the treatment of CHD.

Methods: Network pharamcology was performed to identify the core components, targets, and key genes of Astragalus-Safflower herbal pair (ASHP) for the treatment of CHD. Enrichment analysis was performed to identify overlapping genes. Ultrahigh-performance liquid chromatography coupled with Q-Exactive MS/MS (UHPLC-QE-MS) was used to detect the blood component of rat ASHP drug-containing serum, which is also considered to be the core components of the ASHP. Molecular docking of ASHP core compounds with core proteins of the pyroptosis pathway mediated by the NLR family pyrin domain containing 3 (NLRP3) inflammasomes. In vivo experiments were conducted to verify the effect and mechanism of ASHP in the CHD mice model.

Results: 54 active compounds and 404 target genes were identified from ASHP, and 1576 targets for CHD with 90 overlapping genes for both. IL6, AKT1, IL1B, TP53, VEGFA, PTGS2, MMP9, CCL2, CXCL8 and EGF were the key hub target genes. Enrichment analysis of Kyoto Encyclopedia of Gene and Genome (KEGG) revealed that the NLRP3 inflammasome-mediated signaling pathway was one of the more critical signaling pathways. The UHPLC-QE-MS was used to identify the rat ASHP containing serum enrollment compound as calycosin and isorhamnetin. Molecular docking showed that quercetin, kaempferol, apigenin, calycosin and isorhamnetin possessed good binding sites with NLRP3 and Caspase-1. Animal experiments showed that the expression of NLRP3, Caspase-1, GSDMD, IL-1β mRNA and protein levels were elevated in mouse models of CHD, and decreased after intervention with ASHP.

Conclusions: ASHP can effectively treat CHD, and the mechanism may be related to the inhibition of the NLRP3 inflammasome-mediated pathway.

Keywords: Astragalus-Safflower herb pair; NLRP3 inflammasome; coronary heart disease; network pharmacology; pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carthamus tinctorius*
Caspases
Inflammasomes / genetics
Mice
Molecular Docking Simulation
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
Network Pharmacology
Rats
Tandem Mass Spectrometry

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Caspases