Chlorogenic acid suppresses monocrotaline-induced sinusoidal obstruction syndrome: The potential contribution of NFκB, Egr1, Nrf2, MAPKs and PI3K signals

• CGA attenuated MCT-induced SOS in rats.
• CGA attenuated MCT-induced hepatic inflammation and oxidative injury.
• CGA inhibited MCT-induced transcriptional activation of NFκB and Egr1.
• CGA enhanced Nrf2 transcriptional activation.
• CGA abrogated MCT-induced activation of MAPKs and PI3K signaling pathways.

Hepatic sinusoidal obstruction syndrome (SOS) is a highly lethal liver disease. This study aims to observe the protection and its engaged mechanism of chlorogenic acid (CGA) against monocrotaline (MCT)-induced SOS. Results of detecting liver ascites, measuring serum transaminases, liver histological evaluation and scanning electron microscope observation all demonstrated that CGA prevented MCT-induced SOS in rats. CGA reduced MCT-induced increased liver myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)α and interleukin (IL)-1β mRNA expression, toll-like receptor (TLR)-2,3,6,9 expression, and nuclear factor κB (NFκB) transcriptional activation. CGA also decreased MCT-induced early growth response1 (Egr1) activation. CGA reduced MCT-induced elevated liver malondialdehyde (MDA) amount and enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). CGA blocked MCT-induced PI3K and MAPKs activation. In conclusion, this study demonstrates the protection of CGA against MCT-induced SOS. Transcriptional factor NFκB, Egr1 and Nrf2-regulated inflammation, coagulation-fibrinolysis, and antioxidant, and PI3K and MAPKs all contribute to such protection.

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