title: Quercetin and baicalein suppress monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats.
abstract: 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 (90mg/kg) to induce SOS, and 6, 30h later were orally given with quercetin and baicalein (40mg/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.
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China. Electronic address: shengych@163.com.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
authors.forename: Minwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China. Electronic address: lichenyue1307@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
mesh_terms: D000818:Animals; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D044950:Flavanones; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D051193:Toll-Like Receptors; C006680:baicalein; D016686:Monocrotaline; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Egr1; MAPKs; Nrf2; PI3K; Sinusoidal obstruction syndrome; TLRs/NFκB