Research Article Details

Article ID: A28165
PMID: 16231594
Source: Eur Rev Med Pharmacol Sci
Title: The treatment of NAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.
DOI:

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S08 Lifestyle measures Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise -- -- Details
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
S07 Anti-lipogenesis de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

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
I14 9970 Obesity An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D032 Betaine Chemical drug DB06756 DNMTs stimulant Improve insulin resistance Under clinical trials Details
D225 Metformin Chemical drug DB00331 PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor Improve insulin resistance Under clinical trials Details
D388 Vitamin E Supplement DB00163 NR1I2; ALOX5; DGKA Anti-inflammatory Under clinical trials Details
D038 Biguanide Chemical drug DB13100 -- -- Under clinical trials Details
D366 Thiazolidinediones Chemical drug DB11898 -- -- Under clinical trials Details
D080 Citrulline Chemical drug DB00155 -- -- Under clinical trials Details
D336 Silymarin Biological drug DB14375 -- Antiviral; Antioxidant; Antifibrotic; Anti-inflammatory Under clinical trials Details
D381 Ursodeoxycholic acid Chemical drug DB01586 AKR1C2 inducer Anti-inflammatory Under clinical trials Details
D083 CLA Chemical drug DB01211 KCNH2; SLCO1B1; SLCO1B3 -- 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
D311 Rosiglitazone Chemical drug DB00412 PPARG agonist; PPARA; PPARD Improve insulin resistance Failed in clinical trials Details
D157 Glucophage Chemical drug DB00331 -- -- Under clinical trials Details