†These authors contributed equally.
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-1
