Research Article Details
| Article ID: | A11430 |
| PMID: | 30897538 |
| Source: | Biomed Pharmacother |
| Title: | Biological mechanisms and related natural modulators of liver X receptor in nonalcoholic fatty liver disease. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide health problem, but no approved medical treatment exists so far. Nuclear receptors are one of the drug targets for nonalcoholic steatohepatitis (NASH). Among them, liver X receptor (LXR) has been studied in recent years in tumors, metabolic diseases and inflammatory diseases, but its physiological and pharmacological effects in the treatment of NASH are controversial. Activation of LXR has the potential to modulate cholesterol homeostasis, induce anti-inflammatory effects and increase insulin sensitivity, but liver lipid deposition and hypertriglyceridemia are also increased. Inhibition of liver LXR transcriptional activity in the context of NAFLD can effectively alleviate hepatic steatosis, inflammation, and fibrosis but elevates the risk of potential cardiovascular disease. The contradictory pharmacodynamic effects of LXR in the treatment of NASH increase the difficulty of developing targeted drugs. Moreover, natural compounds play an important part in drug development, and in recent years, some natural compounds have been reported to treat NAFLD by acting on LXR or LXR pathways with fewer adverse reactions, presenting a promising therapeutic prospect. In this review, we discuss the mechanisms of LXR in NASH and summarize the natural products reported to modulate NAFLD via LXR or the LXR pathway, offering an alternative approach for LXR-related drug development in NAFLD. |
| DOI: | 10.1016/j.biopha.2019.108778 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 |