Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte injury.
Salvia plebeia R. Br is a traditional Chinese herb which has been considered as an inflammatory mediator used for treatment of many infectious diseases including hepatitis. Previously, the compound homoplantaginin was isolated in our group. Hence, we evaluated the protective effects of homoplantaginin on hepatocyte injury. Homoplantaginin displayed an antioxidant property in a cell-free system and showed IC(50) of reduction level of DPPH radical at 0.35 microg/ml. In human hepatocyte HL-7702 cells exposed to H(2)O(2), the addition of 0.1-100 microg/ml of homoplantaginin, which did not have a toxic effect on cell viability, significantly reduced lactate dehydrogenase (LDH) leakage, and increased glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in supernatant. In vivo assay, we employed the model of Bacillus Calmette-Guérin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury mice to evaluate efficacy of homoplantaginin. Homoplantaginin (25-100mg/kg) significantly reduced the increase in serum alanine aminotranseferase (ALT) and aspartate aminotransferase (AST), decreased the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The same treatment also reduced the content of thiobarbituric acid-reactive substances (TBARS), elevated the levels of GSH, GSH-Px and SOD in hepatic homogenate. The histopathological analysis showed that the grade of liver injury was ameliorated with reduction of inflammatory cells and necrosis of liver cells in homoplantaginin treatment mice. These results suggest that homoplantaginin has a protective and therapeutic effect on hepatocyte injury, which might be associated with its antioxidant properties.
Qu
Xian-Jun
XJ
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
Xia
Xue
X
Wang
Yuan-Shu
YS
Song
Mei-Juan
MJ
Liu
Li-Li
LL
Xie
Yan-Ying
YY
Cheng
Yan-Na
YN
Liu
Xiang-Juan
XJ
Qiu
Lu-Lu
LL
Xiang
Lan
L
Gao
Jian-Jun
JJ
Zhang
Xiao-Fan
XF
Cui
Shu-Xiang
SX
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D004798:Enzymes / Q000097:blood; D005419:Flavonoids / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007375:Interleukin-1 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents; D027544:Salvia / Q000737:chemistry*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C403862:6-methoxy-4',5-dihydroxyflavone-7-O-glucoside; D000975:Antioxidants; D004798:Enzymes; D005419:Flavonoids; D005960:Glucosides; D007375:Interleukin-1; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase