Cynaropicrin Alleviates Pulmonary Embolism in Rats by Inhibiting the MEK/ERK/Egr-1/TF Signaling Pathway, Suppress Inflammatory Pathways, and Apoptotic Cascades

Background: Cynaropicrin (CYN) exhibits anti-inflammatory and anti-thrombotic properties, but its effects on pulmonary embolism (PE) are poorly understood. Objectives: This study aimed to investigate the effects of CYN on PE induced by autologous blood clots in a rat model and to explore the underlying mechanisms. Materials and Methods: Forty male Wistar rats were divided into four groups: sham, PE, PE + 10 mg CYN, and PE + 25 mg CYN. CYN’s impact on inflammatory factors and coagulation was assessed using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA) for oxidative stress (OS) and inflammatory markers (tissue factor (TF), monocyte chemoattractant protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1)). Real-time polymerase chain reaction (PCR) analyzed the MEK/ERK/early growth response protein 1 (Egr-1)/TF signaling pathway, while immunohistochemistry (IHC) examined caspase-3 and p53 expression in lung tissue. Results: CYN treatment significantly reduced body and lung weights in the PE groups (p < .05). Serum levels of inflammatory markers were elevated in the PE group but decreased with CYN treatment (p < .05). OS markers improved with CYN, and gene expression of MEK/ERK pathway components was reduced (p < .05). CYN also led to dose-dependent decreases in apoptosis markers (caspase-3, p53). Structural improvements in lung tissue were observed via stereological and transmission electron microscopic (TEM) analyses. Conclusion: CYN demonstrated therapeutic effects by inhibiting inflammation and suppressing the MEK/ERK/Egr-1/TF signaling pathway. Further research is warranted to confirm these findings and assess CYN’s safety and efficacy in humans.