| 摘要 |
[Objectives] To investigate the protective effects and underlying mechanisms of agarwood essential oil against isoprenaline (ISO)-induced myocardial ischemia (MI) in mice. [Methods] Utilizing network pharmacology methods, the active components, targets, and MI-related targets of agarwood were identified. Subsequently, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the identified targets. The efficacy and predictive pathways were evaluated using MI mice. Thirty male C57 mice were randomly divided to five groups: the control group (CTL), the model group (MOD), the positive control group (Pro), the low-dose agarwood essential oil group (Y01-L), and the high-dose agarwood essential oil group (Y01-H). Mice in each treatment group received continuous intragastric administration for 14 d. Beginning on day 8, 1 h post administration, mice in all groups except the control group were intraperitoneally injected with ISO at a dose of 10 mL/kg daily for 7 d. The control group received an equivalent volume of normal saline via intraperitoneal injection during this period. One hour following the final administration, blood samples were collected under anesthesia, and the heart was excised and weighed to determine the organ index. The activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in mouse serum were measured using biochemical assay kits. The protein expression levels of HIF-1α, P-AKT, and P-PI3K were analyzed using Western blot assay. [Results] The results of the network pharmacology analysis identified AKT1, MAPK14, and other targets as common to both agarwood and MI. GO functional analysis and KEGG pathway enrichment analysis demonstrated a significant association with the HIF-1α signaling pathway. The validation results in mice demonstrated that the active component, agarwood essential oil Y01, effectively inhibited cardiac swelling induced by ischemia. Serological indicators revealed that, compared to the model group, Y01 dose-dependently decreased serum MDA level and LDH activity (P<0.001) while increasing SOD activity (P<0.01, P<0.001). The Western blot assay demonstrated that Y01 significantly upregulated the protein expression levels of HIF-1α, P-AKT, and P-PI3K. [Conclusions] Y01 has the potential to mitigate myocardial injury induced by ischemia through the modulation of the HIF-1α and AKT/PI3K signaling pathways, thereby enhancing cardiac function. |
