Protective Effect of Matrine on Lithocholic Acid Induced Liver Injury Cell Lines by Regulating PXR-CYP3A4 Pathway
YANG Li-mei1, CHEN Shu-fang2, HUANG Xu-hui2*, ZHUANG Jie1
1. Department of Pharmacy,Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350000, China; 2. Department of Pharmacy, Fujian Provincial Hospital South Branch, Fujian Provincial Hospital Jinshan Branch, Fuzhou 350000, China
Abstract:OBJECTIVE To OBJECTIVE of this study was to explore the protective effect and potential mechanism of matrine (MT) on lithocholine acid (LCA)-induced liver injury Chang-liver and Huh-7 cell lines. METHODS Chang liver cell line and Huh-7 cell lines were respectively cultured in 1640 medium and DMEM medium which contained penicillin and streptomycin. Four groups which were blank group, LCA group, and different doses of MT group (0.5, 1, 2 μmol·L-1) were installed. After intervention with agents, ALT, AST, TBIL, ALP of cells were detected by automatic biochemical analyzer. The expression of PXR and CYP3A4 mRNA was detected by RT-PCR, and the expression of PXR and CYP3A4 protein was detected by Western blot. RESULTS For Chang liver cell, MT significantly decreased ALT, AST, TBiL and ALP levels, up-regulated PXR mRNA expression, down-regulated CYP3A4 mRNA expression, and down-regulated PXR and CYP3A4 protein expression in cells which were treated by LCA. For Huh-7 cell, MT significantly decreased ALT, AST and ALP levels, up-regulated PXR and CYP3A4 mRNA expression and and down-regulated CYP3A4 protein expression in cells which were treated by LCA. CONCLUSION This study shows that MT could improve the liver function index in LCA-induced injury liver cells. The mechanism might be related to the regulation of mRNA and protein expression of PXR and CYP3A4. However, the effects of MT on Chang live cells and Huh-7 cells are different.
ZHANG M F, SHEN Y Q. Research advances on clinical pharmacological action of anti-inflammatory agent and immunosuppressant of matrine[J]. Anti Infect Pharm(抗感染药学), 2018,15(5):737-743.
[2]
YANG L M, HUANG X H, CAO W, et al. Protective effects of matrine on α-naphthl isocyanate-induced cholestatic liver injury in rats[J]. Chin Pharm J(中国药学杂志), 2018, 53(10):783-787.
[3]
LU Y H, YI Y, LONG L, et al. Effects of matrine on renal injury involved in upregulation of renal MCP-1 and NF-κB expression in the mice with lupus nephritis[J]. Chin Pharm J(中国药学杂志), 2010, 45(19):1469-1474.
[4]
LIU J J, MOU Y L. Advances in research on anti-tumor mechanism of matrine[J]. J Chin Pharm(中国药房), 2017, 28 (19):2707-2711.
[5]
WANG F, LI K. Mechanisms of hydrophobic bile acid mediating hepatocyte injury[J]. J Med Postgr(医学研究生学报), 2012, 25(8):882-886.
[6]
WANG Y G, WANG S Q, GAO Y. The induction of CYP3A regulated by pregnane X receptor and its significance in drug metabolism [J]. Acta Pharm Sin(药学学报), 2006, 41(1):1-6.
[7]
BEUERS U, TRAUNER M, JANSEN P, et al. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond[J]. J Hepatol, 2015, 62(S1):25-37.
[8]
XU C, HUANG M, BI H. PXR- and CAR-mediated herbal effect on human diseasesa[J]. Biochim Biophys Act, 2016, 1859(9):1121-1129.
[9]
WANG Y G, ZHANG X X, LI H, et al. Pharmacology research on PXR as a potential target in screening bioactive components of Chinese material medica[J]. China J Chin Mater Med(中国中药杂志), 2015, 40(17):3444-3449.
[10]
XUE C M, ZHANF B, LIN Z J. Study on effect of Curculiginis Rhizoma and its active ingredient on PXR-CYP3A of L02 cells in different states [J]. China J Chin Mater Med(中国中药杂志), 2013, 38(19):3348-3352.
[11]
LU W, QIAN F Y, FENG Z, et al. Paracetamol-induced liver injury via regulating the pregnane X receptor [J]. J Int Pharm Res(国际药学研究杂志), 2018, 45(2):112-118.