| Title |
Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway
|
|---|---|
| Published in |
Drug Design, Development and Therapy, September 2015
|
| DOI | 10.2147/dddt.s90030 |
| Pubmed ID | |
| Authors |
Xiao Ma, Yan-ling Zhao, Yun Zhu, Zhe Chen, Jia-bo Wang, Rui-yu Li, Chang Chen, Shi-zhang Wei, Jian-yu Li, Bing Liu, Rui-lin Wang, Yong-gang Li, Li-fu Wang, Xiao-he Xiao |
| Abstract |
Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 15% |
| Student > Master | 2 | 8% |
| Researcher | 2 | 8% |
| Lecturer | 1 | 4% |
| Student > Doctoral Student | 1 | 4% |
| Other | 4 | 15% |
| Unknown | 12 | 46% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 4 | 15% |
| Medicine and Dentistry | 3 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Philosophy | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 12 | 46% |
Attention Score in Context
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#23,182,177
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Outputs of similar age from Drug Design, Development and Therapy
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