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Detoxification mechanism of psoralea corylifolia reverse compatibility based on the AMPK/GSK-3β/Nrf2 signaling pathway

  • role： First author第一作者
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

  • Introduction：王婧，女，在读硕士生
WANG Jing1,  
  • Affiliation：

    Queen Mary School, Nanchang University, Nanchang 330031, China

WEI Wenxin2,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

LI Xingyu1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

CHEN Sikai1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

ZHANG Mengmeng1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

LI Yao1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

DONG Taiwei1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

GAO Feng1,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

LI Min1,  
  • Affiliation：

    Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712021, China

XI Miaomiao3,  
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

XIE Yundong1,  
  • role： Corresponding author通信作者
  • Affiliation：

    Shaanxi University of Chinese Medicine, Xianyang 712046, China

    Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712021, China

  • Email：weipeifeng@163.com
  • Introduction：Prof. WEI Peifeng, Ph. D., Master’s Supervisor. Second Affiliated Hospital of Shaanxi University of Chinese Medicine, No. 831, Longtaiguan Road, Fengxi New Town, Xixian New District, Xianyang 712021. E-mail: weipeifeng@163.com
WEI Peifeng13*

Resümee

ObjectiveTo investigate the attenuating effect of reverse compatibility of psoralea corylifolia on rat liver and the underlying mechanism.MethodsAccording to the random number table method, 80 SD rats were divided into the blank group, the model group, the psoralea corylifolia group, the psoralea corylifolia + polygonum multiflorum 1∶1 group, the psoralea corylifolia + polygonum multiflorum 1∶2 group, the psoralea corylifolia + polygonum multiflorum 2∶1 group, the psoralea corylifolia + rehmannia glutinosa 1∶1 group, the psoralea corylifolia + schisandra chinensis 1∶1 group, with 10 rats in each group. Rats in all groups except for the blank group were subcutaneously injected with hydrocortisone (25 mg/kg) once a day for 14 days to establish a rat model of kidney yang deficiency. After the model of kidney yang deficiency was established, the rats were given corresponding drugs for 4 weeks; the drug dose was 12.6 g/kg in each group. HE staining was used to observe the pathological changes of rat liver tissue. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin (DBIL) and total bilirubin (TBIL) and the expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in liver tissue were detected by ELISA. The mRNA expression levels of NF-E2-related factor 2 (Nrf2), Kelch-like epichlorohydrin-related protein 1 (Keap1), heme oxygenase-1 (HO-1), and quinone oxidoreductase NADH1 (NQO1) were detected by real-time PCR. The protein expression levels of phosphorylated AMPK (p-AMPK), phosphorylated GSK-3β (p-GSK-3β), Nrf2, and HO-1, which were involved in the AMPK/GSK-3β/Nrf2 signaling pathway, were determined by Western blotting.ResultsCompared with the psoralea corylifolia group, the structure of hepatic lobules in rats was improved and the inflammatory infiltration cells were reduced after the compatibility of psoralea corylifolia and medicinals for replenishing yin such as polygonum multiflorum, rehmannia glutinosa and schisandra chinensis. Compared with the psoralea corylifolia group, the serum levels of AST, ALT, ALP, DBIL, and TBIL of rats in the psoralea corylifolia+ polygonum multiflorum 1∶2 group, the psoralea corylifolia+ rehmannia glutinosa 1∶1 group, the psoralea corylifolia+ schisandra chinensis 1∶1 group were reduced (P<0.01); the expression levels of SOD, GSH-Px and MDA in liver tissue of rats were improved in psoralea corylifolia+ polygonum multiflorum 1∶2 group (P<0.01); the mRNA levels of Nrf2, HO-1, and NQO1 were up-regulated (P<0.01) and the mRNA level of Keap1 was down-regulated (P<0.01) in the psoralea corylifolia+ polygonum multiflorum 1∶2 group; the protein expression levels of p-AMPK, p-GSK-3β, Nrf2, and HO-1 were increased in the psoralea corylifolia+ polygonum multiflorum 1∶2 group, the psoralea corylifolia+ polygonum multiflorum 2∶1 group, the soralea corylifolia+ rehmannia glutinosa 1∶1 group, and the soralea corylifolia+ schisandra chinensis 1∶1 group (P<0.05, P<0.01).ConclusionThe compatibility of psoralea corylifolia and medicinals for replenishing yin polygonum multiflorum, rehmannia glutinosa and schisandra chinensis can improve the liver injury caused by psoralea corylifolia. The mechanism may be to activate the AMPK/GSK-3β/Nrf2 signaling pathway and inhibit the oxidative stress state to play a protective role in the liver. The compatibility ratio of psoralea corylifolia and polygonum multiflorum 1∶2 has the best attenuation effect.

Schlüsselwort

psoralea corylifolia;reverse compatibility;hepatotoxicity;AMPK/GSK-3β/Nrf2 signaling pathway;rats

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