Monotropein alleviates acute pulmonary embolism in rats by inhibiting the NF-κB pathway.

ABSTRACT

OBJECTIVE: This study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment. METHODS: Thirty Sprague Dawley (SD) rats were randomly assigned to five groups (n = 6 per group) sham, Mon (40 mg/kg), APE, APE + 20 mg/kg Mon, and APE + 40 mg/kg Mon. APE was induced via autologous thrombus infusion in all groups except sham and Mon-only groups. We assessed blood gas parameters, lung wet/dry weight (W/D) ratio, and oxidative stress markers. Additionally, excised lung tissues underwent evaluation for serum inflammatory factors via ELISA, apoptotic cells via TUNEL assay, and protein expression via Western blot. RESULTS: Compared to the sham group, APE-induced rats exhibited significantly elevated blood oxygen levels and increased pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-8. Mon treatment effectively mitigated these APE-induced changes, reducing blood oxygen concentration and downregulating IL-1ß and TNF-α levels. Furthermore, Mon demonstrated anti-apoptotic effects by decreasing cleaved caspase-3 and Bax protein levels while upregulating Bcl-2 expression. Mon also suppressed nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation levels of p65/RelA and IκBα proteins, while the total protein level of IκBα was increased with Mon treatment. CONCLUSION: Mon effectively ameliorated lung tissue injury in APE rats by inhibiting apoptosis, attenuating inflammatory responses, and alleviating oxidative stress. These beneficial effects appear to be mediated through modulation of the NF-κB pathway, suggesting Mon as a promising therapeutic candidate for APE treatment.