Protective effect of Compound Ginkgo against acute alcohol-induced liver injury and its mechanism
10.3867/j.issn.1000-3002.2014.03.011
- VernacularTitle:复方银杏制剂对急性酒精性肝损伤小鼠的防护作用及其机制
- Author:
Ping QIU
;
Pingping LIU
;
Desong KONG
;
Xiang LI
;
Huanzhou LI
;
Juanhong WANG
;
Suhua PAN
- Publication Type:Journal Article
- Keywords:
Ginkgo biloba;
liver injury;
oxidative stress;
cytochrome P450 2E1;
NF-E2-related factor 2;
tu mor necrosis factor-α
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(3):373-379
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE ToobservetheprotectiveeffectandmechanismofCompoundGinkgo biloba(CGB)againstalcohol-inducedliverinjury.METHODS MiceweregivenCGB0.125,0.25and 0.75 g·kg -1 ,Ginkgo biloba extract (GBE)0.1 25 g·kg -1 and bifendate(Bif)0.1 5 g·kg -1 for 8 weeks, respectively.At the end of 4th week the mice were given wine by gavage (56% V/V,0.01 L·kg -1 ), and (56% V/V,0.016 L·kg -1 )at the end of the 8th week.The serum was obtained to measure alanine transaminase (GPT),aspartate aminotransaminase (GOT),mitochondrial aspartate aminotransferase (mGOT)and tumor necrosis factor-α(TNF-α).Liver histopathology was revealed by HE staining.The protein expression of cytochrome P450 (CYP)2E1 ,NF-E2-related factor 2 (Nrf2)and TNF-αin the liverwasanalyzedbyWesternblotting.RESULTS Comparedwithnormalcontrolgroup,theactivitiesof GOT and mGOT were increased in model group (P<0.01 ).Compared with model group,CGB 0.25 and 0.75 g·kg -1 groups and Bif 0.1 5 g·kg -1 group significantly decreased the activity of GOT and mGOT in serum (P<0.05,P<0.01 ),while there was no significant difference between these groups in serum GPT activity (P>0.05).Fatty degeneration and neutrophil infiltration were significantly ameliora-ted in CGB 0.25 and 0.75 g·kg -1 groups.Preliminary mechanism research showed CGB not only increased the protein expression of Nrf2 with a positive dose-effect relationship (r=0.942,P<0.01 ), but reduced the protein expression of hepatic CYP2 E1 and the level of TNF-αin hepatic tissue with a negative dose-effect relationship (r=-0.987,P<0.05;r=-0.940,P<0.05).In addition.The level ofTNF-αwasalsosignificantlydecreasedintheserum(P<0.05,P<0.01).CONCLUSION CGB may protect the liver fro m acute alcoholic injury and the mechanis m may be that it increases the protein expression of Nrf2,restrains the protein expression of hepatic CYP2E1 and TNF-αand reduces the TNF-αlevel in the serum.