Research Article Details
| Article ID: | A35878 |
| PMID: | 19513529 |
| Source: | Int J Mol Med |
| Title: | Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue. |
| Abstract: | We examined whether or not epigallocatechin-3-gallate (EGCG) improves liver injury of nonalcoholic steatohepatitis (NASH) model mice expressing nuclear sterol regulatory element-binding protein 1c (nSREBP-1c) in adipose tissue. nSREBP-1c transgenic C57BL6 mice aged 30 weeks were divided into group 1 (no treatment), group 2 (ascorbic acid alone), group 3 (ascorbic acid and 0.05% EGCG), and group 4 (ascorbic acid and 0.1% EGCG). At 42 weeks, we performed measurement of liver weight to body weight, biochemical assays, morphometry of liver specimens, immunohistochemistry for 8-hydro-2'-deoxyguanosine (8-OhdG), and Western blotting for insulin and TNF-alpha signalings. Ratio of liver weight to body weight in the high dose EGCG-treated group (group 4) was significantly lower than those of groups 1 and 2 (p<0.05 and <0.01, respectively). Blood ALT, glucose, total cholesterol, and triglyceride levels of group 4 were significantly low compared with those of the EGCG-non-treated group (groups 1 and 2) (p<0.05, respectively). The degrees of steatosis, inflammation, ballooning hepatocytes and Mallory-Denk bodies in group 4 significantly improved compared with those in other groups (p<0.05, respectively). The 8-OhdG immunolocalization in liver tissues of the group 4 obviously decreased compared with those of groups 2 and 3. For Western blotting, the expressions of insulin receptor substrate-1 (IRS-1) and phosphorylated IRS-1 (pIRS-1) in liver tissues of group 4 increased compared with those of groups 2 and 3. On the other hand, the expressions of pAkt, pIKKbeta and pNF-kappaB decreased compared with those of groups 2 and 3. From these results, EGCG reduces inflammation, insulin resistance and oxidative stress, and suppresses liver injury in nSREBP-1c transgenic mice. |
| DOI: | 10.3892/ijmm_00000200 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D386 | Vitamin C | Supplement | DB00126 | PLOD2 cofactor; PLOD3 cofactor; DBH cofactor; P3H1 cofactor; P3H2 cofactor; P3H3 cofactor; PLOD1 cofactor | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |