Gegen Qinlian Decoction abates nonalcoholic steatohepatitis associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of toll-like receptor 4 signaling pathways

Autor: Cao Zheng, Xiao-quan Luo, Ke-zhong Deng, Li-fen Zhou, Xiao Qin, Ya-nan Xue, Chen Chen, Min Shi, Ying-qian Cao, Jun-qing Sheng, Tong-tong Liu, Chang-hua Zhang
Rok vydání: 2020
Předmět:
0301 basic medicine
Lipopolysaccharides
Proteomics
Lipopolysaccharide
Anti-Inflammatory Agents
Pharmacology
medicine.disease_cause
Antioxidants
chemistry.chemical_compound
Mice
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Non-alcoholic steatohepatitis
Toll-like receptor
Chemistry
General Medicine
030220 oncology & carcinogenesis
GNMT
Cytokines
lipids (amino acids
peptides
and proteins)
Female
medicine.symptom
Signal transduction
Inflammation Mediators
Signal Transduction
Inflammation
RM1-950
Models
Biological
Cell Line
03 medical and health sciences
medicine
Animals
Gegen Qinlian Decoction
Gene Expression Profiling
nutritional and metabolic diseases
Lipid metabolism
Lipid Metabolism
Rats
Toll-Like Receptor 4
Disease Models
Animal
Oxidative Stress
Hepatic lipid metabolism
030104 developmental biology
TLR4
Therapeutics. Pharmacology
Transcriptome
Oxidative stress
Biomarkers
Drugs
Chinese Herbal
Zdroj: Biomedicine & Pharmacotherapy, Vol 126, Iss, Pp 110076-(2020)
ISSN: 1950-6007
Popis: Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.
Databáze: OpenAIRE
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