The protective effects of total saponins from Ornithogalum saundersiae (Liliaceae) on acute hepatic failure induced by lipopolysaccharide and D-galactosamine in mice.
BACKGROUND
This study examined the protective effects of total saponins from Ornithogalum saundersiae (Liliaceae) on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure.


METHODS
Total saponins of Ornithogalum saundersiae (Liliaceae) (OC) were prepared with ethyl alcohol extract from bulbs of the plant. Mice were given an intraperitoneal injection of D-GalN (700 mg/kg)/LPS (10 μg/kg). OC (100 mg/kg, 200 mg/kg and 300 mg/kg) was administered orally for 3 days continuously, and at the last day at 1 h before the D-GalN/LPS injection. Mice were sacrificed at 8 h after the D-GalN/LPS injection. The liver injury was assessed biochemically, investigating aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione (GSH) activities, and the expressions of caspase-3 and hypoxia inducible factor-1α (HIF-1α) as well. Tumor necrosis factor (TNF-α) content was measured after D-GalN/LPS induced 1 h by ELISA assay. The survival rates after application of OC in 24 h also were observed.


RESULTS
D-GalN/LPS increased the serum aminotransferase levels and lipid peroxidation, while decreased the reduced glutathione level. The pretreatment with OC attenuated these changes in a dose-dependent manner. Elevation of TNF-α level and activation of caspase-3, HIF-1α were observed in the D-GalN/LPS group, which was attenuated by OC. The survival rate of the OC groups was significantly higher than that of the D-GalN/LPS group.


CONCLUSIONS
Protection afforded by OC against D-GalN/LPS-induced fulminant hepatic failure is the result of reduced oxidative stress, inhibited expression of caspase-3, HIF-1α, and anti-apoptotic activity.
Ying-Wan
Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, No. 1829, Juzi Street, Yanji 133002, Jilin Province, China.
Wu
Yan-Ling
YL
Feng
Xiao-Chun
XC
Lian
Li-Hua
LH
Jiang
Ying-Zi
YZ
Nan
Ji-Xing
JX
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D005688:Galactosamine; D005978:Glutathione / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D031442:Ornithogalum; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D020011:Protective Agents / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D020011:Protective Agents; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D005978:Glutathione