Research Article Details
| Article ID: | A07818 |
| PMID: | 32346285 |
| Source: | Drug Des Devel Ther |
| Title: | Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway. |
| Abstract: | Purpose: Nonalcoholic fatty liver disease (NAFLD) has become a predictor of death in many diseases. This study was carried out to investigate the therapeutic effect of Radix Polygoni Multiflori Preparata (RPMP) and its main component emodin on egg yolk powder-induced NAFLD in zebrafish. Further investigation was performed to explore whether emodin was the main component of RPMP for the treatment of NAFLD as well as the underlying therapeutic mechanism of RPMP and emodin. Methods: Zebrafish were divided into control group, egg yolk powder group, RPMP group and emodin group. The obesity of zebrafish was evaluated by body weight, body length and BMI. The content of lipid was detected by triglyceride (TG), total cholesterol (TC) reagent kit and the fatty acid was detected by nonesterified free fatty acids (NEFA) reagent kit. HE staining was used to detect the histological structure of liver. Whole-mount Oil red O staining and Frozen oil red O staining were carried out to investigate the lipid accumulation in liver. KEGG and STRING databases were performed to analyze the potential role of AMPK between insulin resistance (IR) and fatty acid oxidation. Western blot and RT-qPCR were carried out for mechanism research. Results: RPMP and emodin significantly reduced zebrafish weight, body length and BMI. Both RPMP and emodin treatment could reduce the lipid deposition in zebrafish liver. RPMP significantly reduced the content of TG. However, emodin significantly reduced the contents of TG, TC and NEFA in zebrafish with NAFLD. The protein interaction network indicated that AMPK participated in both IR and fatty acid oxidation. Further investigation indicated that RPMP and emodin reduced hepatic lipogenesis via up-regulating the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT2), amp-activated protein kinase alpha (AMPKα), proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase 1a (CPT-1a) and acyl-coenzyme A oxidase 1 (ACOX1). Conclusion: These findings suggest that emodin is the main component of RPMP for the treatment of NAFLD, which is closely related to the regulation of AMPK signaling pathway which increases IR and fatty acid oxidation. |
| DOI: | 10.2147/DDDT.S243893 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T21 | Diacylglycerol O-acyltransferase 2 | DGAT2 | inhibitor | Enzyme | Q96PD7 | DGAT2_HUMAN | 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 |
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D596 | Emodin | Chemical drug | -- | DNA synthesis inhibitors; Protein synthesis inhibitors; Protein tyrosine kinase inhibitors; RNA synthesis inhibitors | Anti-fibrosis | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |