Research Article Details
| Article ID: | A21089 |
| PMID: | 25542756 |
| Source: | Eur J Pharmacol |
| Title: | Ameliorative effect of nicorandil on high fat diet induced non-alcoholic fatty liver disease in rats. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is an accumulation of excessive amounts of fats in the liver that is not caused by alcohol consumption. It is considered as the most common liver disease in Western societies. The aim of this study is to investigate the possible protective effects of nicorandil and pioglitazone, the benefits of their combination and the possible mechanism underlie these effects in NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. In the next eight weeks, rats were fed the HFD along with pioglitazone (4 mg/kg) or nicorandil in two dose levels (3 or 15 mg/kg), alone or in combination. Chronic HFD administration resulted in significant elevations in serum levels of liver enzymes, total cholesterol, triglycerides, glucose, insulin and HOMA-IR index as compared with the control group. This was coupled with significant increments in liver triglycerides, MDA content and TNF-α as well as a significant reduction in liver GSH content. In comparison with the control group; liver expression of NF-κB was significantly elevated while liver eNOS expression and nitric oxide content were significantly decreased in HFD group. Treatment with pioglitazone or nicorandil either alone or in combination successfully ameliorated the deleterious effects of HFD on the all previous parameters. In conclusion, this investigation indicates a novel role of nicorandil in rats with NAFLD. This effect is mediated through, nitric oxide donor, antioxidant and anti-inflammatory properties, leading to improvement of insulin resistance. It is worth mentioning that the combinations were more effective than the individual drugs. |
| DOI: | 10.1016/j.ejphar.2014.12.017 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D158 | Glutathione | Chemical drug | DB00143 | MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor | -- | Under clinical trials | Details |