The stems of Syringa oblata Lindl. exert cardioprotective effects against acute myocardial ischemia by inhibiting the TLR4/MyD88/NF-κB and NLRP3 inflammasome signaling pathways in mice.

ETHNOPHARMACOLOGICAL RELEVANCE

The stripped roots and stems of Syringa oblata Lindl. (SO), a Mongolian and Tibetan folk medicinal plant, are renowned for their traditional use against "Khii", pain relief, and heat clearing. It is used to treat cardiovascular diseases (CVDs), upset, insomnia, and other symptoms and is commonly used as a substitute for another plant known as S. pinnatifolia, which is used in Mongolian folk medicine.

OBJECTIVE

This study analyzed the cardioprotective effect of SO against myocardial ischemia and the underlying mechanism through cardiac inflammation and the pyroptosis pathway.

MATERIALS AND METHODS

This study developed an acute myocardial infarction (AMI) model by ligating the left anterior descending coronary artery (LAD) in mice. Additionally, the cardioprotective effect was determined via echocardiography, detection of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin-I (cTnI) detection, and hematoxylin and eosin (HE) staining. Lipopolysaccharide (LPS) plus adenosine triphosphate (ATP) was used to stimulate RAW264.7 mouse monocyte macrophages to induce pyroptosis. The cell morphology was monitored by scanning electron microscopy. The underlying mechanisms were assessed via immunohistochemistry, immunofluorescence staining, and western blotting (WB).

RESULTS

SO (40-160 mg/kg) significantly decreased the values of left ventricular internal dimension diastole (LVID; d) and left ventricular internal dimension systole (LVID; s), increased the ejection fraction (EF) and fractional shortening (FS), reduced serum levels of CK-MB, LDH, and cTnI, and mitigated microstructural destruction of MI tissue. SO at concentrations of 1.25-10 μg/mL significantly inhibited nitrogen monoxide (NO) production. At 10 μg/mL, it strongly suppressed pyroptosis while maintaining the morphological features of RAW264.7 cells. These findings suggest that SO has significant anti-myocardial ischemic effects. Administration of SO (40-160 mg/kg) in mice significantly reduced interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels, accompanied by decreased fluorescence intensities of the apoptosis speck-like protein containing a caspase recruitment domain (ASC), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and cysteinyl aspartate-specific protease-1 (caspase-1) proteins. WB analysis revealed that SO (40-160 mg/kg) treatment reduced inflammatory protein levels, including toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Additionally, the phosphorylation levels of nuclear factor-kappa-B (NF-κB) and inhibitors of NF-kappa-Bα (IκBα) were suppressed. Moreover, levels of pyroptosis-related proteins, including ASC, caspase-1, NLRP3, and gasdermin D (GSDMD), were reduced.

CONCLUSIONS

SO may protect against myocardial ischemia through modulation of the TLR4/MyD88/NF-κB inflammatory pathway and suppression of NLRP3 inflammasome-mediated pyroptosis. This study demonstrates that SO alleviates AMI by mechanisms involving anti-inflammatory effects and pyroptosis inhibition, establishing an experimental basis for evaluating its therapeutic efficacy and clinical translation.