Research Article Details
| Article ID: | A12076 |
| PMID: | 30611993 |
| Source: | Biomed Pharmacother |
| Title: | Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress. |
| Abstract: | BACKGROUND: Chronic consumption of fructose causes obesity and nonalcoholic fatty liver disease (NAFLD). Currently available therapies have limitations; hence there is a need to screen new molecules. Plumbagin is a naphthoquinone present in the roots of Plumbago species which has hypolipidemic and hepatoprotective activities. METHODS: Rats were divided into five groups: normal control, disease control, orlistat, plumbagin (0.5 mg/kg and 1 mg/kg body weight). The normal control group received standard diet and drinking water while the remaining groups received fructose in drinking water alongwith the standard diet for 16 weeks. Orlistat and plumbagin were administered orally from the 9th week-16th week. The body weight, calorie intake and weights of visceral adipose tissue and liver were determined. Blood glucose, insulin, lipid profile and liver function tests were determined. Antioxidant and inflammatory parameters, lipids and collagen were determined in the liver. Gene expression of SREBP-1c and PPAR-α were determined in the liver. The histopathology of the adipose tissue and liver were also studied. RESULTS: Fructose feeding resulted in a significant increase in the body weight gain, calorie intake, visceral fat, liver weight, blood glucose and insulin and caused dyslipidemia which was mitigated by plumbagin. Plumbagin exerted antioxidant, anti-inflammatory and anti-fibrotic effects in the liver and reduced the hepatic lipids. Plumbagin reduced the gene expression of SREBP-1c and increased that of PPAR-α. Plumbagin reduced the hypertrophy of adipocytes and ameliorated the degenerative changes in the liver. CONCLUSION: Plumbagin thus seems to be a promising molecule for the management of obesity and NAFLD. |
| DOI: | 10.1016/j.biopha.2018.12.139 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D260 | Orlistat | Chemical drug | DB01083 | FASN inhibitor | Enhance lipid metabolism | Under clinical trials | Details |
| D142 | Fructose | Chemical drug | DB04173 | -- | Intravenous nutrition drug | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |