scholarly journals Protective Effects ofDracocephalum heterophyllumin ConA-Induced Acute Hepatitis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zheng ◽  
Qilan Wang ◽  
Xiaohua Lu ◽  
Qiangqiang Shi ◽  
Junhui Zou ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Herbal Medicine ◽  
Liver Injury ◽  
Chinese Herbal Medicine ◽  
Tumor Necrosis ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Protective Effects ◽  
Chinese Herbal ◽  
Necrosis Factor

Dracocephalum heterophyllum(DH) is a Chinese herbal medicine used in treating hepatitis. However, the protective effects and pharmacological mechanisms of DH in hepatitis are unknown. In this study, we found that pretreatment with DH extract significantly ameliorated liver injury and suppressed the production of inflammatory cytokines, including tumor necrosis factor (TNF-α) and interferon-γ(IFN-γ) in Concanavalin A- (ConA-) induced hepatitis (CIH). DH recruited more CD11b+Gr1+myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of macrophages (Kupffer cells) in the liver. The present work explores DH as an effective hepatoprotective medicine to inhibit inflammation and liver injury caused by hepatitis.

scholarly journals LGR4 protects hepatocytes from injury in mouse

2019 ◽  
Vol 316 (1) ◽  
pp. G123-G131
Author(s):  
Ziru Li ◽  
Shiying Liu ◽  
Jianing Lou ◽  
Michael Mulholland ◽  
Weizhen Zhang
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Liver Injury ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Expression Profiles ◽  
Acute Injury ◽  
Protective Effects ◽  
Factor Α ◽  
Necrosis Factor

Leucine-rich repeat G protein-coupled receptors (LGRs) and their endogenous ligands R-spondin1–4 (Rspo) are critical in embryonic development and in maintenance of stem cells. The functions of the Rspo-LGR system in differentiated cells remain uncharacterized. In this study, the expression profiles of LGRs and Rspos were characterized in mature hepatocytes. A liver-specific knockout of LGR4 in mouse was generated and used to study hepatic ischemia/reperfusion-induced injury (HIRI) as well as lipopolysaccharide/ D- galactosamine (LPS/D-Gal)-induced liver injury. We have demonstrated that, in adult liver, LGR4 is expressed in hepatocytes and responds to Rspo1 with internalization. Rspo1 is responsive to various nutritional states and to mTOR signaling. Activation of LGR4 by Rspo1 significantly reduced tumor necrosis factor-α (TNFα)-induced cell death, and levels of NF-κB-p65 and caspase-3 in cultured hepatocytes. Knockdown of hepatic LGR4 rendered hepatocytes more vulnerable to TNFα-induced damage in cultured primary cells and in the setting of HIRI and LPS/D-Gal-induced liver injury. Rspo1 potentiated both basal and Wnt3a-induced stabilization of β-catenin. Disruption of β-catenin signaling reversed the protective effects of Rspo1 on TNFα-induced hepatocyte toxicity. LGR4 knockdown increased nuclear translocation of NF-κB-p65 in response to acute injury. Overexpression of IKKβ attenuated the protective effects of Rspo1 on TNFα-induced cell death. In conclusion, the Rspo1-LGR4 system represents a novel pathway for cytoprotection and modulation of stress-induced tissue damage. NEW & NOTEWORTHY Functional LGR4 is present in mature hepatocytes. R-spodin1 protects hepatocytes from tumor necrosis factor-α-induced cell death. Liver-specific knockdown of LGR4 renders liver more susceptible to acute injury. LGR4 protects hepatocytes from injury by inhibition of NF-κB signaling.

scholarly journals The pathogenic roles of tumor necrosis factor receptor p55 in acetaminophen-induced liver injury in mice

2003 ◽  
Vol 75 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Yuko Ishida ◽  
Toshikazu Kondo ◽  
Koichi Tsuneyama ◽  
Peirong Lu ◽  
Tatsunori Takayasu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Injury ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals Chinese Herbal Medicine Hepatotoxicity: The Evaluation and Recognization Based on Large-scale Evidence Database

2019 ◽  
Vol 20 (2) ◽  
pp. 138-146 ◽  
Author(s):  
Zhi Liu ◽  
Xin He ◽  
Lili Wang ◽  
Yunhua Zhang ◽  
Yue Hai ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Liver Injury ◽  
Chinese Herbal Medicine ◽  
Large Scale ◽  
Evaluation Method ◽  
Liver Toxicity ◽  
Assessment Method ◽  
Chinese Herbs ◽  
Data Resource ◽  
Chinese Herbal

Background:Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI).Methods:First, the database would provide full profile of HILI from the basic ingredients to clinical outcomes by the most advanced algorithms of artificial intelligence, and it is also possible that we can predict possibilities of HILI after patients taking Chinese herbs by individual patient evaluation and prediction. Second, the database would solve the chaos and lack of the relevant data faced by the current basic research and clinical practice of Chinese Herbal Medicine. Third, we can also screen the susceptible patients from the database and thus prevent the accidents of HILI from the very beginning.Results:The Roussel Uclaf Causality Assessment Method (RUCAM) is the most accepted method to evaluate DILI, but at present before using the RUCAM evaluation method, data resource collection and analysis are yet to be perfected. Based on existing research on drug-metabolizing enzymes mediating reactive metabolites (RMs), the aim of this study is to explore the possibilities and methods of building multidimensional hierarchical database composing of RMs evidence library, Chinese herbal evidence library, and individualized reports evidence library of herb induced liver injury HILI.Conclusion:The potential benefits lie in its ability to organize, use vast amounts of evidence and use big data mining techniques at the center for Chinese herbal medicine liver toxicity research, which is the most difficult key point of scientific research to be investigated in the next few years.

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