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Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats.
Qian, Hui; Shi, Jian; Fan, Ting-Ting; Lv, Jiao; Chen, Si-Wen; Song, Chun-Yan; Zheng, Zhi-Wu; Xie, Wei-Fen; Chen, Yue-Xiang.
Afiliación
  • Qian H; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Shi J; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Fan TT; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Lv J; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Chen SW; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Song CY; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Zheng ZW; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Xie WF; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
  • Chen YX; Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
World J Gastroenterol ; 20(7): 1822-32, 2014 Feb 21.
Article en En | MEDLINE | ID: mdl-24587659
ABSTRACT

AIM:

To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.

METHODS:

Sophocarpine was injected intraperitoneally in two distinct rat hepatic fibrosis models induced either by dimethylnitrosamine or bile duct ligation. Masson's trichrome staining, Sirius red staining and hepatic hydroxyproline level were used for collagen determination. Primary hepatic stellate cells (HSCs) were isolated and treated with different concentrations of sophocarpine. Real-time reverse transcription-polymerase chain reaction was used to detect the mRNA levels of fibrotic markers and cytokines. The expression of pathway proteins was measured by Western blot. The Cell Counting Kit-8 test was used to detect the proliferation rate of activated HSCs treated with a gradient concentration of sophocarpine.

RESULTS:

Sophocarpine decreased serum levels of aminotransferases and total bilirubin in rats under chronic insult. Moreover, administration of sophocarpine suppressed extracellular matrix deposition and prevented the development of hepatic fibrosis. Furthermore, sophocarpine inhibited the expression of α-smooth muscle actin (SMA), interleukin (IL)-6, transforming growth factor-ß1 (TGF-ß1), Toll-like receptor 4 (TLR4), and extracellular-related kinase (ERK) in rats. Sophocarpine also down-regulated the mRNA expression of α-SMA, collagen I, collagen III, TGF-ß1, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1, and decreased protein levels of TLR4, p-ERK, p-JNK, p-P38 and p-IKK in vitro after Lipopolysaccharide induction. In addition, sophocarpine inhibited the proliferation of HSCs accompanied by a decrease in the expression of Cyclin D1. The protein level of proliferating cell nuclear antigen was decreased in activated HSCs following a gradient concentration of sophocarpine.

CONCLUSION:

Sophocarpine can alleviate liver fibrosis mainly by inhibiting the TLR4 pathway. Sophocarpine may be a potential chemotherapeutic agent for chronic liver diseases.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Alcaloides / Receptor Toll-Like 4 / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: World J Gastroenterol Asunto de la revista: GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Alcaloides / Receptor Toll-Like 4 / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: World J Gastroenterol Asunto de la revista: GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: China