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.

Safflower has long been used to treat coronary heart disease (CHD). However, the underlying mechanism remains unclear. The goal of this study was to predict the therapeutic effect of safflower against CHD using a network pharmacology and to explore the underlying pharmacological mechanisms. Firstly, we obtained relative compounds of safflower based on the TCMSP database. The TCMSP and PubChem databases were used to predict targets of these active compounds. Then, we built CHD-related targets by the DisGeNET database. The protein-protein interaction (PPI) network graph of overlapping genes was obtained after supplying the common targets of safflower and CHD into the STRING database. The PPI network was then used to determine the top ten most significant hub genes. Furthermore, the DAVID database was utilized for the enrichment analysis on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To validate these results, a cell model of CHD was established in EAhy926cells using oxidized low-density lipoprotein (ox-LDL). Safflower was determined to have 189 active compounds. The TCMSP and PubChem databases were used to predict 573 targets of these active compounds. The DisGeNET database was used to identify 1576 genes involved in the progression of CHD. The top ten hub genes were ALB, IL6, IL1B, VEGFA, STAT3, MMP9, TLR4, CCL2, CXCL8, and IL10. GO functional enrichment analysis yielded 92 entries for biological process (BP), 47 entries for cellular component (CC), 31 entries for molecular function (MF), and 20 signaling pathways, which were obtained from KEGG pathway enrichment screening. Based on these findings, the FoxO signaling pathway is critical in the treatment of CHD by safflower. The in vitro results showed that safflower had an ameliorating effect on ox-LDL-induced apoptosis and mitochondrial membrane potential. The western blot results showed that safflower decreased Bax expression and acetylation of FoxO1 proteins while increasing the expression of Bcl-2 and SIRT1 proteins. Safflower can be used in multiple pathways during CHD treatment and can exert anti-apoptotic effects by regulating the expression of Bax, Bcl-2, and SIRT1/FoxO1 signaling pathway-related proteins.

Brain endothelial cells (BECs) are situated at the interface between the bloodstream and the brain, serving a crucial function in the development and maturation of the brain, particularly in upholding the integrity of the blood-brain barrier (BBB). Consequently, any modifications or gradual breakdown of the endothelium can significantly disrupt brain homeostasis. Ischemic stroke (IS), characterized by the progressive compromise of the BBB and increased BECs mortality, stands as a prominent global cause of mortality and disability. This review will utilize recent research to explore mechanisms underlying death.