Saponins from Panax japonicus protect against alcohol-induced hepatic injury in mice by up-regulating the expression of GPX3, SOD1 and SOD3.
OBJECTIVE
The purpose of this study was to investigate the possible mechanism(s) of saponins from Panax japonicus (SPJ) on alcohol-induced hepatic damage in mice.


METHODS
SPJ were identified by high performance liquid chromatography-evaporative light scattering detection-mass spectrometry (LC-ELSD-MS). Non-toxic concentrations of SPJ were assayed on alcohol-induced hepatic injury in male ICR mice and human hepatic cells. The protective effects were evaluated by biochemical values, histopathological observations and the relative gene expression. Results. In vitro, SPJ showed significant hydroxyl radical scavenging capacity. In vivo, SPJ (50 mg/kg) could rectify the pathological changes of aspartate transaminase, alanine transaminase, malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) caused by alcohol metabolism to normal levels except for hepatic GSH and CAT. In hepatic cells, the results were in agreement with foregoing results determined in mice after pretreatment of SPJ (100 microg/ml). RT-PCR results showed that CAT, GPX and SOD mRNA decreased by alcohol metabolism were reversed, in which GPX3, SOD1 and SOD3 could return to a normal level, but CAT, GPX1 and SOD2 mRNA were still evidently lower than the control. Histopathological observations provided supportive evidence for biochemical analyses.


CONCLUSIONS
SPJ plays an important role in the protection of the structure and function of hepatic mitochondria and karyon by directly scavenging reactive oxygen species/free radicals and up-regulating the expression of antioxidant enzymes (SOD, GPX and CAT), especially to GPX3, SOD1 and SOD3.
Li
You-Gui
YG
College of Animal Science, Zhejiang University, Hangzhou 310029, China.
Ji
Dong-Feng
DF
Zhong
Shi
S
Shi
Lian-Gen
LG
Hu
Gui-Yan
GY
Chen
Shi
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D005894:Panax / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D012503:Saponins; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1