Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice
| Autor: | Zhiyong Weng, Jing Xie, Jingzhou Mu, Jiehua Hu, Li Lihua, Chenjuan Yao, Xuefeng Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Necrosis dehydroandrographolide Extrahepatic Cholestasis Gastroenterology digestive system 03 medical and health sciences Hydroxyproline chemistry.chemical_compound 0302 clinical medicine Cholestasis Fibrosis Internal medicine medicine liver adaptive response Bile duct business.industry obstructive cholestasis medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis Hepatic stellate cell Liver function medicine.symptom business anti-fibrosis formation Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Zhiyong Weng 1 , Xuefeng Liu 1 , Jiehua Hu 2 , Jingzhou Mu 3 , Jing Xie 1 , Chenjuan Yao 4 and Lihua Li 1 1 Department of Cell Biology, Jinzhou Medical University, Jinzhou, PR China 2 Naval University of Engineering, Logistics College, Information Center, Tianjin, PR China 3 Department of Physiology, Dalian Medical University, Dalian, PR China 4 Department of Molecular Oral Physiology, The University of Tokushima Graduate School, Tokushima, Japan Correspondence to: Lihua Li, email: lilihua1018@sina.com Keywords: dehydroandrographolide, obstructive cholestasis, liver adaptive response, anti-fibrosis formation Received: April 15, 2017 Accepted: August 23, 2017 Published: September 23, 2017 ABSTRACT Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. Results: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. Conclusions: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction. |
| Databáze: | OpenAIRE |
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