Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress.

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.