Effect of matrine on primary human hepatocytes in vitro

被引:25
作者
Gong, Xiaobing [1 ]
Gao, Yuan [1 ]
Guo, Guoqing [2 ]
Vondran, Florian W. R. [3 ]
Schwartlander, Ruth [3 ]
Efimova, Ekaterina [3 ]
Pless, Gesine [3 ]
Sauera, Igor M. [3 ]
Neuhaus, Peter [3 ]
机构
[1] Jinan Univ, Dept Gastroenterol, Affiliated Hosp 1, Guangzhou 510630, Guangdong, Peoples R China
[2] Jinan Univ, Dept Anat, Coll Med, Guangzhou 510630, Guangdong, Peoples R China
[3] Univ Med Berlin, Dept Gen Visceral & Transplantat Surg, Berlin, Germany
关键词
Primary human hepatocytes; Matrine; ECOD; CYP450; Apoptosis; CHRONIC HEPATITIS-B; NITRIC-OXIDE SYNTHASE; RAT HEPATOCYTES; DOWN-REGULATION; LIVER-CELLS; INFECTION; ETHOXYRESORUFIN; TRANSPLANTATION; MAINTENANCE; METABOLISM;
D O I
10.1007/s10616-013-9680-1
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Matrine is a bioactive component of the traditional Chinese medical herb Sophora flavescens that has been used in China to treat various kinds of diseases including virus hepatitis. However, the molecular mechanisms underlying its hepatoprotective effects remains elusive. In the present study, primary human hepatocytes were employed to elucidate the protective effects and molecular mechanisms of matrine. We observed that low concentrations of matrine had no significant impact on albumin secretion, but high concentrations (> 140 mg/L) of matrine decreased the albumin secretion in hepatocytes. Western blot data indicated that matrine at 140 mg/L at 72 h induced protein expression of CYP2A6, CYP2B6 and CYP3A4. Furthermore, high concentrations of matrine reduced LDH and AST levels and were cytotoxic to hepatocytes, leading to a decreased cell viability and total protein amount. Moreover, low concentrations of matrine, enhanced the ECOD activity and decreased the level of NO2 (-) induced by cytokines in human hepatocytes. Taken together, the present study sheds novel light on the molecular mechanisms of matrine and potential application of matrine in hepatic diseases.
引用
收藏
页码:255 / 265
页数:11
相关论文
共 42 条
[1]   Irological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapy [J].
Akuta, N ;
Suzuki, F ;
Kobayashi, M ;
Matsuda, M ;
Sato, J ;
Takagi, K ;
Tsubota, A ;
Suzuki, Y ;
Hosaka, T ;
Someya, T ;
Kobayashi, M ;
Saitoh, S ;
Arase, Y ;
Ikeda, K ;
Kumada, H .
JOURNAL OF MEDICAL VIROLOGY, 2003, 71 (04) :504-510
[2]   CRITERIA OF VIABILITY OF ISOLATED LIVER-CELLS [J].
BAUR, H ;
KASPEREK, S ;
PFAFF, E .
HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE, 1975, 356 (06) :827-838
[3]   EFFECT OF ALBUMIN ON METABOLISM OF ETHOXYRESORUFIN THROUGH O-DEETHYLATION AND SULFATE-CONJUGATION USING ISOLATED RAT HEPATOCYTES [J].
BURKE, MD ;
ORRENIUS, S .
BIOCHEMICAL PHARMACOLOGY, 1978, 27 (11) :1533-1538
[4]  
BURKE MD, 1974, DRUG METAB DISPOS, V2, P583
[5]   Nitric oxide release and enhancement of lipid peroxidation in regenerating rat liver [J].
Carnovale, CE ;
Scapini, C ;
Alvarez, MD ;
Favre, C ;
Monti, J ;
Carrillo, MC .
JOURNAL OF HEPATOLOGY, 2000, 32 (05) :798-804
[6]   A NEW TECHNIQUE FOR ISOLATING AND CULTURING HUMAN HEPATOCYTES FROM WHOLE OR SPLIT LIVERS NOT USED FOR TRANSPLANTATION [J].
DORKO, K ;
FREESWICK, PD ;
BARTOLI, F ;
CICALESE, L ;
BARDSLEY, BA ;
TZAKIS, A ;
NUSSLER, AK .
CELL TRANSPLANTATION, 1994, 3 (05) :387-395
[7]  
Dufour DR, 2000, CLIN CHEM, V46, P2027
[8]   Side effects of interferon-α in treating hepatitis C virus infection [J].
Fontaine, H ;
Pol, S .
TRANSPLANTATION PROCEEDINGS, 2001, 33 (03) :2327-2329
[9]   7-ETHOXYCOUMARIN O-DEETHYLASE INDUCTION BY PHENOBARBITONE AND 1,2-BENZANTHRACENE IN PRIMARY MAINTENANCE CULTURES OF ADULT-RAT HEPATOCYTES [J].
FRY, JR ;
WIEBKIN, P ;
BRIDGES, JW .
BIOCHEMICAL PHARMACOLOGY, 1980, 29 (04) :577-581
[10]   Liver disease selectively modulates cytochrome P450-mediated metabolism [J].
Frye, Reginald F. ;
Zgheib, Nathalie K. ;
Matzke, Gary R. ;
Chaves-Gnecco, Diego ;
Rabinovitz, Mordechai ;
Shaikh, Obaid S. ;
Branch, Robert A. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2006, 80 (03) :235-245