Flos Puerariae，Hoveniae Semen and Their Combinations Treat Oxidative Stress in Mice with Acute Alcoholic Liver Injury via Keap1/Nrf2/ARE Signaling Pathway
10.13422/j.cnki.syfjx.20222140
- VernacularTitle:基于Keap1/Nrf2/ARE信号通路探讨葛花、枳椇子及其配伍对急性酒精性肝损伤小鼠抗氧化应激的作用机制
- Author:
Wan XU
1
;
Na LI
1
;
Haiyan LIU
1
;
Linlin XIU
1
;
Xue YU
1
;
Shaohong CHEN
1
;
Gansheng ZHONG
1
Author Information
1. Beijing University of Chinese Medicine， Beijing 100029， China
- Publication Type:Journal Article
- Keywords:
Flos Puerariae;
Hoveniae Semen;
acute alcoholic liver injury;
antioxidation;
Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):37-44
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of Hoveniae Semen， Flos Puerariae and their combinations on acute alcoholic liver disease and provide a scientific basis for the drug use in clinical practice and the research on other alcoholic diseases. MethodThe acute alcoholic liver injury model of mice was established by one-time gavage with 56% （V/V） Hongxing Erguotou liquor （12 mL·kg-1）. One hundred and twenty male ICR mice were randomly assigned into blank group， model group， silybin group， Flos Puerariae group， Hoveniae Semen group， and Flos Puerariae-Hoveniae Semen combination groups （ratios of 1∶1， 1∶2 and 2∶1， respectively）， with 15 mice in each group. Each group was administrated with 10 mL·kg-1 corresponding preventive drugs for 3 days by gavage. Except the blank group， the other groups were given Erguotou liquor by gavage at 12 mL·kg-1. The mice were sacrificed 12 h after drinking for the observation of liver function and oxidative stress. The pathological changes of liver were observed via hematoxylin-eosin （HE） staining. Western blot was employed to determine the expression levels of proteins in the Kelch-like Ech-associated protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of related genes. ResultCompared with control group， the modeling elevated the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and alkaline phosphatase （ALP） in the serum and the content of malondialdehyde （MDA） and reactive oxygen species （ROS） in liver tissue （P<0.01） and decreased the activities of glutathione （GSH） and superoxide dismutase （SOD） （P<0.01）. The mRNA and protein expressions of Keap1 were significantly increased （P<0.05，P<0.01）， mRNA and protein expressions of Nrf2 were significantly decreased （P<0.01）. Compared with model group， Flos Puerariae-Hoveniae Semen 2∶1 lowered the levels of ALT， AST and ALP in the serum （P<0.01） and MDA and ROS in the liver （P<0.01）， and increased the activities of GSH and SOD （P<0.01）. Moreover， it alleviated the hepatic steatosis injury， up-regulated mRNA and protein levels of Nrf2 （P<0.01）， and down-regulated the mRNA and protein levels of Keap1 （P<0.01）. ConclusionFlos Puerariae， Hoveniae Semen and their combinations may exert the pre-protective effect on acute alcoholic liver injury in mice by regulating the Keap1/Nrf2/ARE pathway in the liver and restoring the liver oxidative balance destroyed by ethanol to inhibit the development of alcoholic liver disease .
