Erxian decoction (EXD) is an empirical formula for treating cardiovascular disease, our previous work has shown that EXD could improve the cardiovascular structure and function in ovariectomized (OVX) rats, but its pharmacological mechanism is still unclear. Network pharmacology was utilized to assess the key active components and central targets of EXD in treating postmenopausal cardiovascular disease. Then, an OVX rat model was established, HE staining and transmission electron microscope were utilized to observe myocardial tissue morphology, TUNEL staining was utilized to detect cardiomyocyte apoptosis, western blot, and ELISA were used to confirm efficacy and pathway of EXD. The network pharmacology prediction results showed that 129 common targets were identified by intersecting EXD targets and postmenopausal cardiovascular disease targets, including AKT1, TNF, IL-6, IL-1β, PTGS2 and other core targets, apoptosis, PI3K/AKT, and other signaling pathways may be closely related to postmenopausal cardiovascular disease. After ovariectomy, the myocardial tissue of rats was damaged, the expression level of PI3K/AKT pathway-related molecules in the myocardial tissue were decreased, the apoptosis index of cardiomyocytes was increased, and the levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were enhanced. EXD intervention could improve myocardial tissue injury, EXD could up-regulate the protein expression of PI3K and p-AKT in myocardial tissue, and thereby prevent myocardial cell apoptosis. At the same time, EXD downregulated the levels of inflammatory factors in serum of ovariectomized rats. EXD may prevent myocardial tissue damage through induction of the PI3K/AKT signaling pathway, thereby reducing cardiomyocyte apoptosis and inflammation. EXD may be a potential drug for the treatment of postmenopausal cardiovascular disease.

Aims. Abnormal changes in cardiac function have been reported in menopausal women, but there are few clinical studies on this topic. Erxian decoction (EXD) is a classic prescription that is widely used in the treatment of female menopausal diseases. The purpose of this study was to investigate the dynamic evolution of cardiac function and glucose and lipid metabolism in ovariectomized (OVX) rats and the intervention effect of EXD. Materials and Methods. The OVX climacteric rat model was established by bilateral ovariectomy. After successful modeling, the rats were randomly divided into four groups: the sham operation (SHAM) group (equal volumes of purified water), OVX group (equal volumes of purified water), estradiol (E₂) group (1.8 × 10⁻⁴ g/kg), and EXD group (9 g/kg). Each group of rats was treated for 16 weeks. At the 4^th, 8^th, 12^th, and 16^th weeks after treatment, the cardiac function of the rats in each group was evaluated by ultrasound. The coaxial method was used to measure blood pressure (BP). Serum endothelin-1 (ET-1) and angiotensin-2 (Ang II) levels were determined by the enzyme-linked immunosorbent assay (ELISA). The strip method was used to measure fasting blood glucose (FBG). The serum total cholesterol (TC) and triglyceride (TG) levels of rats were measured with the oxidase method. Direct methods were used to measure serum high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. At week 16 of dosing, serum E₂ levels were determined by E₂ radioimmunoassay. The myocardium and uterus of the rats in each group were stained with HE (hematoxylin-eosin). The ultrastructure of the rat myocardium was observed by electron microscopy. Results. After the 16^th week of treatment, the serum E₂ level decreased ( ), and the uterus was atrophied in OVX rats. The cardiac ejection fraction (EF%) decreased at 4 weeks after treatment, and systolic and diastolic function decreased after 12 weeks. After the 16^th week, the EF%, which reflects the “pump” function of the heart, decreased significantly ( or ). At the 4^th, 8^th, 12^th, and 16^th weeks of treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean pressure (MBP) of the rats in the OVX group increased with time ( or ). The serum ET-1 and Ang II levels of rats in the OVX group increased ( or ). In the OVX group, FBG was increased ( or ), and blood lipids, especially LDL-C, were significantly increased ( or ). After the 16^th week of treatment, the myocardial tissue of OVX rats showed obvious pathological changes. EXD significantly increased serum E₂ levels ( ), decreased ET-1 and Ang II levels ( ), reduced the cardiac function risk factors BP, FBG, and blood lipids, and significantly improved cardiac function and structural changes in OVX rats ( or ). Conclusions. EXD can improve abnormal cardiac structure and function in OVX rats.

Coronary heart disease (CHD) is a global cardiovascular disease with high morbidity and mortality, and its complex pathological mechanism poses great challenges to clinical prevention and treatment. Paeoniflorin (PA), a monoterpene glycoside active ingredient from Ranunculaceae plants, has shown potential in cardiovascular protection, but its specific anti-CHD molecular targets and systematic regulatory networks remain unclear. In this study, a mouse model of CHD was established, and a multi-omics strategy combining label-free quantitative proteomics and metabolomics was adopted to explore the mechanism of PA in treating CHD. The results showed that PA significantly improved cardiac function, alleviated myocardial pathological injury and fibrosis, and regulated lipid metabolism in CHD model mice, with the high-dose group showing the optimal effect. Proteomic analysis identified 51 key differentially expressed proteins (DEPs) reversed by PA, which were mainly enriched in complement and coagulation cascades, and neutrophil extracellular trap formation pathways, with the C3-Cfd-C3aR signaling axis as the core hub. Further verification confirmed that PA could downregulate the expression of C3, Cfd, C3aR, and their downstream molecule BTK, thereby inhibiting myocardial inflammatory response and cardiomyocyte apoptosis. In addition, PA downregulated the expression of platelet activation markers ITGA2B/ITGB3. Metabolomic analysis revealed that PA reversed 57 abnormal metabolites in CHD mice, which were enriched in GABAergic synapse, retrograde endocannabinoid signaling and other pathways. Molecular docking confirmed that PA could stably bind to C3, Cfd, C3aR, BTK, and ITGA2B/ITGB3 with strong binding activity. In conclusion, PA exerts anti-CHD effects through a multi-target and multi-pathway synergism, mainly by targeting the C3-Cfd-C3aR axis to inhibit inflammation, apoptosis and platelet activation, and regulating metabolic disorders. This study provides experimental evidence and theoretical support for the clinical application of PA as a multi-target therapeutic drug for CHD.

This study aimed to systematically elucidate the antihyperlipidemic mechanism of paeoniflorin, and we adopted an integrated multi-omics strategy to screen the key molecular targets and regulatory pathways involved in its action, followed by experimental validation to verify the potential regulatory effects of paeoniflorin on the screened targets and metabolic processes. Rats with high-fat diet-induced hyperlipidemia received paeoniflorin treatment. Liver histopathology was evaluated using hematoxylin–eosin and Oil Red O staining. Serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bile acids, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen were measured using a biochemical analyzer. Integrated multi-omics analyses were performed to investigate paeoniflorin’s lipid-lowering mechanism. Critical pathways and targets identified were validated using Western blotting. Paeoniflorin alleviated pathological liver damage in hyperlipidemic rats and improved blood lipid levels, coagulation function, and liver function markers. Multi-omics analyses verified that paeoniflorin downregulated the expression of TREM-1, TLR4, NF-κB, TNF-α, and IL-1β, thereby alleviating hepatic inflammation. Paeoniflorin also upregulated the expression of low-density lipoprotein receptors (LDLR), liver X receptor alpha (LXRα), and ATP-binding cassette subfamily G member 1 (ABCG1), while downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, contributing to balanced cholesterol metabolism. Paeoniflorin normalized glycerophospholipid and branched-chain amino acid metabolism, which correlated with reduced inflammation and improved cholesterol metabolism. Paeoniflorin ameliorates hyperlipidemia through multitarget mechanisms, potentially by suppressing the TREM-1-TLR4-NF-κB signaling pathway to reduce inflammation and by regulating cholesterol metabolism via the PCSK9-LDLR and LXRα-ABCG1 pathways.

Background: Coronary heart disease (CHD) has a high global disease burden. According to traditional Chinese medicine theory, the main syndrome type of CHD is the syndrome of intermingled phlegm and blood stasis (SI-GPBS). Tanyu Tongzhi Decoction (TYTZD) exerts clear cardioprotective effects on CHD patients with SI-GPBS, while its specific regulatory mechanism remains unclear. Methods: Clinical serum proteomics and network pharmacology were used to screen key targets and pathways for CHD with SI-GPBS. An APOE^−/− mouse model of CHD complicated with SI-GPBS was established and treated with TYTZD. Transcriptomics, proteomics and WGCNA were combined to screen core genes, with Western blotting, immunofluorescence, co-localization analysis and Carstairs staining for target verification and observation of coronary microthrombosis and endothelial injury. Results: A total of 754 differentially expressed proteins were identified in CHD patients with SI-GPBS, significantly enriched in the platelet activation pathway, with ITGA2B as the upregulated core hub protein. Network pharmacology found 94 active ingredients and 144 therapeutic targets of TYTZD for CHD with SI-GPBS, and key components bound well with ITGA2B. In APOE^−/− mice with SI-GPBS, TYTZD improved cardiac function, reduced blood lipids, myocardial enzymes, aortic lipid deposition and myocardial damage, downregulated ITGA2B, F2RL2, FGA and FGB, inhibited integrin αIIbβ3 signaling, restrained endothelial activation and reduced coronary microthrombosis. Conclusions: TYTZD treats CHD with SI-GPBS mainly by inhibiting platelet activation, improving endothelial dysfunction, and reducing coronary microthrombosis. This study provides experimental basis for TYTZD’s clinical application in CHD with SI-GPBS and new ideas for TCM syndrome–disease combination research.