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

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 me...

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Main Authors: Yong Yuan, Huajiang Liu, Qingwen Meng
Format: Article
Language:English
Published: IMR Press 2023-05-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805094
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author Yong Yuan
Huajiang Liu
Qingwen Meng
author_facet Yong Yuan
Huajiang Liu
Qingwen Meng
author_sort Yong Yuan
collection DOAJ
description 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.
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spelling doaj.art-4a593428a6a945ce94f3b5550abd7ad22023-06-01T02:53:04ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-05-012859410.31083/j.fbl2805094S2768-6701(23)00794-3The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental VerificationYong Yuan0Huajiang Liu1Qingwen Meng2College of Pediatrics, Hainan Medical University, 571199 Haikou, Hainan, ChinaDepartment of Interventional Vascular Surgery, The First Affiliated Hospital of Hainan Medical University, 570100 Haikou, Hainan, ChinaHainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan Medical University, 571199 Haikou, Hainan, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805094coronary heart diseaseastragalus-safflower herb pairnetwork pharmacologynlrp3 inflammasomepyroptosis
spellingShingle Yong Yuan
Huajiang Liu
Qingwen Meng
The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
Frontiers in Bioscience-Landmark
coronary heart disease
astragalus-safflower herb pair
network pharmacology
nlrp3 inflammasome
pyroptosis
title The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
title_full The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
title_fullStr The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
title_full_unstemmed The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
title_short The Cardioprotective Effects and Mechanisms of Astragalus-Safflower Herb Pairs on Coronary Heart Disease Identified by Network Pharmacology and Experimental Verification
title_sort cardioprotective effects and mechanisms of astragalus safflower herb pairs on coronary heart disease identified by network pharmacology and experimental verification
topic coronary heart disease
astragalus-safflower herb pair
network pharmacology
nlrp3 inflammasome
pyroptosis
url https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805094
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