Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid accumulation in human L02 hepatocytes.
OBJECTIVE
To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanol-induced lipid deposition in human L02 hepatocytes.


METHODS
L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl-tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively.


RESULTS
Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content (9.69±0.22 μg/mg protein vs. 4.93±0.49 μg/mg protein, P<0.01), and ROS formation (7254.8±385.7 vs. 5825.2±375.9, P<0.01). Meanwhile, improvements in mitochondrial membrane potential (10655.33±331.34 vs. 11129.52±262.35, P<0.05) and ATP level (1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P<0.01) were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression (P<0.01) and upregulate PPARα expression (P<0.01) in ethanol-treated cells.


CONCLUSIONS
Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPARα expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.
Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, Medical College, Jinan University, Guangzhou, 510632, China.
Chao-Feng
CF
Hu
Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, 518020, China.
Li-Ping
LP
Sun
Department of Traditional Chinese Medicine, Medical College, Jinan University, Guangzhou, 510632, China.
Qin-He
QH
Yang
Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, Medical College, Jinan University, Guangzhou, 510632, China. tldx2012@sina.com.
Da-Xiang
DX
Lu
Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, Medical College, Jinan University, Guangzhou, 510632, China.
Sen
S
Luo
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D000431:Ethanol; D036145:Ginsenosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D018547:Plant Stems / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D036145:Ginsenosides; D047493:PPAR alpha; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000431:Ethanol; D000255:Adenosine Triphosphate; D019392:Cytochrome P-450 CYP2E1
cytochrome P450 2E1; ginsenosides; hepatocyte steatosis; mitochondrial function; peroxisome proliferator-activated receptor α; reactive oxygen species