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| Study on the intervention effect of baicalein derivative on acute hepatic encephalopathy in rats |
| Hits 626 Download times 469 Received:July 21, 2021 |
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| DOI
10.11656/j.issn.1672-1519.2021.11.20 |
| Key Words
hepatic encephalopathy;baicalein derivative;blood ammonia;neurotransmitter;PI3K/AKT signaling pathway |
| Author Name | Affiliation | E-mail | | FAN Baishuang | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WU Zijun | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LIU Shihao | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LI Siqin | State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Guangdong Pharmaceutical University, Guangzhou 510006, China | | | WANG Lili | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | HE Xin | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Guangdong Pharmaceutical University, Guangzhou 510006, China | hexintn@163.com |
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| Abstract
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| [Objective] The protective effect of baicalein derivative (disulfonate baicalein,DB) on acute hepatic encephalopathy by constructing a thioacetamide (TAA) induced acute hepatic encephalopathy rats was studied. [Methods] Wistar rats,as the research objects,were randomly divided into control group,model group,DB groups (6.25,25,100 mg/kg) and positive drug group (lactulose,6 g/kg). The rats in each group were intragastric the corresponding dose of drugs,while the rats in the control group and the model group were given the same amount of normal saline. During this period,the behavioral changes of rats were detected by the morris water maze test. The rats were sacrificed after 7 days of administration and colon contents,hepatic and brain tissue were collected. The content of blood ammonia was detected by rapid ammonia analyzer. The pH of colon contents was measured by pH meter. The concentrations of aspartate aminotransferase (AST),alanine aminotransferase (ALT),alkaline phosphatase (ALP),and total bilirubin (TBiL) in serum were determined by automatic biochemical analyzer. HE staining was performed for hepatic tissues. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the contents of gamma aminobutyric acid (GABA) and glutamic acid (Glu) in prefrontal cortex were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phosphatidylinositol 3 kinase (PI3K) and phosphorylated protein kinase B (p-AKT) in prefrontal cortex were detected by Western bloting. [Results] Compared with the model group,DB low,middle and high dose groups reduced the mortality of rats with hepatic encephalopathy,enhanced rat's learning and memory ability,and improved the pathological damage and fibrosis of liver tissue. The middle and high dose groups significantly reduced blood ammonia and pH of colon contents (P<0.01),also decreased the serum levels of ALT,AST,ALP,TBiL,TNF-α and IL-6 (P<0.05, 0.01),decreased GABA content in prefrontal cortex (P<0.01),increased Glu content in prefrontal cortex. The middle dose group could decrease the protein expression levels of PI3K and p-AKT in prefrontal cortex (P<0.01). [Conclusion] DB can improve the learning and memory ability and liver function of rats with TAA induced acute hepatic encephalopathy,reduce ammonia levels,inhibit the expression of inflammatory factors,and regulate neurotransmitters (GABA and Glu) levels in prefrontal cortex. Its mechanism may be related to the regulation of PI3K/AKT signaling pathway. |
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