Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways. 2019

Ning Liu, and Jiao Feng, and Xiya Lu, and Zhilu Yao, and Qing Liu, and Yang Lv, and Yuru Han, and Jingfan Deng, and Yingqun Zhou
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.

OBJECTIVE Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. METHODS Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl4) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl4 model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor β1 (TGF-β1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-β1-mediated Smad3 and p38 MAPK signaling pathways.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
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
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
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
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D048051 p38 Mitogen-Activated Protein Kinases A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens. Mitogen-Activated Protein Kinase p38,p38 Mitogen-Activated Protein Kinase,p38 MAP Kinase,p38 MAPK,p38 Protein Kinase,p38 SAPK,MAP Kinase, p38,MAPK, p38,Mitogen Activated Protein Kinase p38,Protein Kinase, p38,p38 Mitogen Activated Protein Kinase,p38 Mitogen Activated Protein Kinases
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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