Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocytes and in mice fed a high-fat diet

Authors: NAM, WOO - Ajou University Of Korea; NAM, SEOK HYUN - Ajou University Of Korea; KIM, SUNG PHIL - Ajou University Of Korea; Levin, Carol; Friedman, Mendel

Submitted to: BMC Complementary and Alternative Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/19/2019
Publication Date: 12/11/2019
Citation: Nam, W., Nam, S., Kim, S., Levin, C.E., Friedman, M. 2019. Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocytes and in mice fed a high-fat diet. BMC Complementary and Alternative Medicine. 19:364. https://doi.org/10.1186/s12906-019-2756-5.
DOI: https://doi.org/10.1186/s12906-019-2756-5

Interpretive Summary: Interest in plant-derived purpurin arises from the fact that it has been reported to have numerous biological activities in cells and rodents. Our study defined the molecular, biochemical, and toxicity changes induced by purpurin in vitro in 3T3-L1 preadipocyte fat cells; and confirmed the expected reduction in weight gain and expression of associated obesity biomarkers in mice fed a high-fat diet supplemented with purpurin. Mice on a high-fat diet with added purpurin experienced a 54.6% reduction in weight gain compared to those on the control diet without added purpurin, and the effect was dose-dependent. Purpurin also acted as a strong antioxidant in fat cells, reduced plasma glucose, cholesterol, and triglyceride content of the mice, and protected the liver against the accumulation of adipose tissue, cholesterol, and triglycerides. These observations and the studies by other investigators imply that dietary purpurin has the potential to help overcome the adverse effects of metabolic and chronic diseases such as cancer, diabetes, and heart disease.

Technical Abstract: The present study investigates the inhibitory effect of the plant-derived compound purpurin (1,2,4-trihydroxyanthraquinone) on adipogenesis in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet. The treatment of the cells with purpurin during adipocyte differentiation resulted in decreased levels of intracellular reactive oxygen species (ROS) and in the membrane potential of the mitochondria. The decreased membrane potential seems to be responsible for the concurrent reduction in ATP production that likely resulted in reduced energy consumption, as well in activation of AMPK (adenosine 5'-monophosphate-activated protein kinase), a target for the treatment of obesity and diabetes. The reduction of ROS and activation of AMPK by the purpurin treatment also led to a decreased expression of PPAR-gamma (peroxisome proliferator activate receptor-gamma) and C/EBPa (enhancer binding protein a) that are related to adipocyte differentiation and to decreased intracellular triglyceride accumulation. Collectively, these results showed that purpurin can effectively inhibit the differentiation of the preadipocyte fat cells in vitro, which led us to the investigation of whether the effects in vitro could be observed in vivo. Mice were fed diets with a 60% fat content with added purpurin at concentrations of 40 and 80 mg/kg. After 10 weeks on the high-fat diet, the weights of the purpurin-fed mice decreased significantly compared with a purpurin-free high-fat standard diet. The decrease in weight gain by 54.6% was accompanied by reductions in blood glucose, triglyceride, and total cholesterol levels to normal levels observed with the control diet. In addition, the livers of purpurin-fed mice contained significantly reduced triglyceride and total cholesterol accumulation, as well as decreased white adipocyte tissue diameters. The results show that purpurin had strong anti-adipogenic effects in a cell line that produces adipocytes and the in vitro anti-obesity effect was confirmed in vivo in an oral feeding study using experimental obese mice on a high-fat diet. The observed inhibition of adipocyte differentiation in the fat cells and in the changes in obesity-related biological markers in mice resulting in inhibition of obesity merits confirmation in clinical studies.