Quercetin and baicalein suppress monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats. 2017

Jiaqi Zhang, and Yuchen Sheng, and Liang Shi, and Zhiyong Zheng, and Minwei Chen, and Bin Lu, and Lili Ji
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.

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.

UI MeSH Term Description Entries
D008297 Male Males
D011794 Quercetin A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin. 3,3',4',5,7-Pentahydroxyflavone,Dikvertin
D006504 Hepatic Veno-Occlusive Disease Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction. Sinusoidal Obstruction Syndrome,Veno-Occlusive Disease, Hepatic,Hepatic Veno Occlusive Disease,Disease, Hepatic Veno-Occlusive,Hepatic Veno-Occlusive Diseases,Syndrome, Sinusoidal Obstruction,Veno Occlusive Disease, Hepatic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016686 Monocrotaline A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment. Monocrotaline Hydrochloride (13alpha,14alpha)-Isomer,Monocrotaline, (all-xi)-Isomer
D044950 Flavanones A group of FLAVONOIDS characterized with a 4-ketone. 2-Phenyl-Benzopyran-4-Ones,2 Phenyl Benzopyran 4 Ones
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D051193 Toll-Like Receptors A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS. Receptors, Toll-Like,Toll-Like Receptor,Receptor, Toll-Like,Receptors, Toll Like,Toll Like Receptor,Toll Like Receptors
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2

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