Quercetin and baicalein suppress monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats

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• 作者：Jiaqi Zhang^a ; Yuchen Sheng^b ; ^{shengych@163.com} ; Liang Shi^a ; Zhiyong Zheng^a ; Minwei Chen^a ; Bin Lu^a ; Lili Ji^a ; ^{lichenyue1307@126.com}
• 关键词：Sinusoidal obstruction syndrome ; TLRs/NFκB ; Egr1 ; Nrf2 ; MAPKs ; PI3K
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：795
• 期：Complete
• 页码：160-168
• 全文大小：2575 K
• 卷排序：795

文摘

Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCT)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MCT (90 mg/kg) to induce SOS, and 6, 30 h later were orally given with quercetin and baicalein (40 mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats. Quercetin and baicalein reduced the increased metalloproteinase-9 (MMP-9) expression, liver myeloperoxidase (MPO) activity, toll-like receptor (TLR)-2,3,6,9 expression and nuclear factor κB (NFκB) transcriptional activation induced by MCT. Quercetin and baicalein reduced MCT-induced nuclear translocation of early growth response1 (Egr1) and increased expression of Serpine1 and tissue factor (TF). Quercetin and baicalein reduced MCT-induced increased liver malondialdehyde (MDA) amount and enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Quercetin and baicalein also abrogated MCT-induced activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling cascades. In conclusion, this study demonstrated the protection of quercetin and baicalein against MCT-induced SOS in rats, indicating the potential application of them for the treatment of SOS in clinic. Transcriptional factor NFκB, Egr1 and Nrf2-regulated inflammation, coagulation-fibrinolysis and antioxidant, and PI3K and MAPKs signaling cascades are all involved such protection.