Research Article Details
| Article ID: | A50810 |
| PMID: | 35218717 |
| Source: | Eur J Pharmacol |
| Title: | HA-20 prevents hepatocyte steatosis in metabolic-associated fatty liver disease via regulating Ca2+ relative signalling pathways. |
| Abstract: | Metabolic-associated fatty liver disease (MAFLD) is caused by hepatocyte steatosis and is associated with obesity, type II diabetes, and heart disease. There are currently no effective drugs to treat MAFLD. This study explored the effect of HA-20, an oleanolic acid derivative, on hepatocyte steatosis in MAFLD. HepG2, L02, and AML12 cells were developed using oleic acid for in vitro MAFLD cell assays, and a high-fat diet + high-fructose diet-induced (HFHF) MAFLD mouse model was established for in vivo studies. The results demonstrated that HA-20 prevented hepatocyte steatosis in cell assays and caused 26.3, 57.7 and 70.0% inhibition of triglyceride (TG) levels in the 5.0, 10.0 and 20.0 μM HA-20 groups, respectively. The EC50 values of HA-20 treatment in HepG2, L02 and AML12 cells were 9.7 ± 0.6 μM, 42.4 ± 3.5 μM and 71.0 ± 14.7 μM, respectively. HA-20 also prevented hepatocyte steatosis in the MAFLD mouse model, the liver triglyceride contents were 2.3 ± 0.4 and 1.5 ± 0.2 mmol/L in the 2.5 and 5.0 mg/kg/day HA-20 groups, lower than 6.2 ± 0.7 mmol/L in the HFHF group and 3.3 ± 0.4 mmol/L in the metformin group. Further mechanistic investigation revealed that HA-20 increased the phosphorylation of calmodulin-dependent protein kinase kinase (p-CaMKK) and the phosphorylation of AMP-activated protein kinase (p-AMPK), at least partially by increasing intracellular Ca2+ concentration, which suppressed lipogenesis and enhanced β-oxidation. Our findings provide new insight into preventing MAFLD by increasing Ca2+ and suggest that HA-20 possesses therapeutic potential for MAFLD management. |
| DOI: | 10.1016/j.ejphar.2022.174838 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D252 | Oleanolic Acid | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |
| D142 | Fructose | Chemical drug | DB04173 | -- | Intravenous nutrition drug | Under clinical trials | Details |