Research Article Details
| Article ID: | A11958 |
| PMID: | 30668424 |
| Source: | Phytomedicine |
| Title: | Lycopus lucidus Turcz. ex Benth. Attenuates free fatty acid-induced steatosis in HepG2 cells and non-alcoholic fatty liver disease in high-fat diet-induced obese mice. |
| Abstract: | BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic diseases such as obesity and insulin resistance. PURPOSE: We studied whether an ethanol extract of Lycopus lucidus Turcz. ex Benth (LLE) exhibited effects on lipid metabolism in NAFLD. STUDY DESIGN: An in vitro modelwas established by treatment of HepG2 cells with a 1 mM free fatty acid (FFA) mixture (oleic acid/palmitic acid, 2:1). C57BL/6 mice were fed a high-fat diet (HFD; 60 kcal% fat) for 14 weeks to induce obesity and were treated with or without LLE (100 or 200  mg/kg daily by oral gavage). METHODS: HepG2 cells were exposed to 1 mM FFA, with or without LLE (250 - 1000  mg/ml). Intracellular lipid contents were measured by Oil Red O staining and a Nile Red assay. The body weight, relative liver weight, hepatic lipids, triglycerides (TGs), and total cholesterol (TC) were measured in the mice. Serum alanine aminotransferase (ALT), TG, TC, glucose, insulin, leptin, and tumor necrosis factor-alpha (TNF-α) levels were determined by biochemical or enzyme-linked immunosorbent assays. Histologic analysis was performed in the liver. Western blotting and quantitative real-time polymerase chain reaction were used to analyze the expression of key enzymes of hepatic lipid metabolism. RESULTS: LLE significantly decreased the intracellular lipid accumulation in FFA-treated HepG2 cells. LLE not only remarkably decreased the expression of lipogenesis genes but also increased β-oxidation in FFA-induced HepG2 cells. In the in vivo study, LLE treatment significantly decreased the body weight, relative liver weight, serum ALT, TC, and low-density lipoprotein cholesterol, as well as the serum glucose, insulin, leptin, and TNF-α levels in HFD-fed mice. The hepatic TG and TC contents were significantly reduced in the LLE-treated groups. Western blot analysis showed that the expression of sterol-regulatory element-binding protein 1 decreased, while that of phosphorylated AMP-activated protein kinase and peroxisome proliferator-activated receptor α increased in the LLE-treated mice. CONCLUSION: These results suggest that LLE may exert protective effects against NAFLD-related obesity and metabolic disease. |
| DOI: | 10.1016/j.phymed.2018.07.008 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| 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 |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |