Research Article Details
| Article ID: | A02118 |
| PMID: | 34500407 |
| Source: | Curr Opin Pharmacol |
| Title: | A double-edged sword: The Kelch-like ECH-associated protein 1-nuclear factor erythroid-derived 2-related factor 2-antioxidant response element pathway targeted pharmacological modulation in nonalcoholic fatty liver disease. |
| Abstract: | Nutraceuticals activating the Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway are widely used for nonalcoholic fatty liver disease (NAFLD) because no specific drugs are approved yet. The pathology of NAFLD is summarized as the 'two-hit' hypothesis. The 'first hit' includes insulin resistance and lipid accumulation. Oxidative stress, lipid peroxidation, and inflammation are regarded as the 'second hit'. Now there is controversial evidence about the roles of the Keap1-Nrf2-ARE pathway and its activators in NAFLD. When the 'first hit' occurs, the hepatocyte-specific Nrf2 deficiency reduces insulin resistance and significantly attenuates lipid accumulation. However, when the 'second hit' occurs, Nrf2 activation reduces oxidative stress and combats inflammation. We reviewed the roles of the Keap1-Nrf2-ARE pathway as a double-edged sword in the development of NAFLD, its inhibitors as a novel therapeutic approach for early NAFLD, and the nutraceutical character of its activators. |
| DOI: | 10.1016/j.coph.2021.07.021 |
| 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 |