Protective effects of the total saponins from Dioscorea nipponica Makino against carbon tetrachloride-induced liver injury in mice through suppression of apoptosis and inflammation.
The present study was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against CCl₄-induced hepato-toxicity in mice. The mice were orally administrated with TSDN for seven days and then given CCl₄ (0.3%, 10 ml/kg i.p.). The results showed that TSDN significantly attenuated the activities of ALT and AST, consistent with hematoxylin-eosin staining. The ALP levels and relative liver weight were significantly decreased by TSDN compared with model group. Moreover, TSDN dramatically decreased MDA, iNOS and NO levels, while the levels of GSH, GSH-Px and SOD were increased. Further investigations showed that TSDN inhibited CCl₄-induced metabolic activation and CYP2E1 expression, down-regulated the levels of MAPKs phosphorylation, NF-κB, HMGB1, COX-2 as well as effectively suppressed the expressions of Caspase-3, Caspase-9, PARP and Bak. Quantitative real-time PCR assay demonstrated that TSDN obviously decreased the gene expressions of TNF-a, IL-1β, IL-6, IL-10, Fas, FasL, Bax as well as modulated Bcl-2 mRNA level. This is the first time to report the protective actions of the TSDN against CCl₄-induced liver damage in mice through suppression of inflammation and apoptosis. This natural product should be developed as a new drug for treatment of liver injury in future.
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Hao
H
Yu
The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Lingli
L
Zheng
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China; Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Dalian 116011, China.
Lianhong
L
Yin
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Lina
L
Xu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China; The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Yan
Y
Qi
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Xu
X
Han
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Youwei
Y
Xu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Kexin
K
Liu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province 116044, China; Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Dalian 116011, China. Electronic address: jinyongpeng2008@126.com.
Jinyong
J
Peng
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D027742:Dioscorea; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry; D012503:Saponins / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010936:Plant Extracts; D012503:Saponins; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1
CCl(4)-induced hepatotoxicity; D. nipponica Makino; Liver injury; Natural product; Total saponins