The aim of this study was to investigate the anti-obesity and antihyperlipidemic efficacy and molecular mechanisms of Aster spathulifolius Maxim extract (ASE) in rats with high-fat diet (HFD)-induced obesity. Rats were separately fed a normal diet or a HFD for 8 weeks, then they were treated with ASE (62.5, 125, or 250 mg/kg) for another 4.5 weeks. The ASE supplementation significantly lowered body weight gain, visceral fat pad weights, serum lipid levels, as well as hepatic lipid levels in HFD-induced obese rats. Histological analysis showed that the ASE-treated group showed lowered numbers of lipid droplets and smaller size of adipocytes compared to the HFD group. To understand the mechanism of action of ASE, the expression of genes and proteins involved in obesity were measured in liver and skeletal muscle. The expression of fatty acid oxidation and thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3) of HFD-induced obese rats were increased by ASE treatment. On the other hand, ASE treatment resulted in decreased expression of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c, ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT). Furthermore, ASE treatment increased the level of phosphorylated AMPKα in obese rats. Similarly, the level of phosphorylated ACC, a target protein of AMPKα in ASE groups, was increased by ASE treatment compared with the HFD group. These results suggest that ASE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obese rats by increasing lipid metabolism through the regulation of AMPK activity and the expression of genes and proteins involved in lipolysis and lipogenesis.

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among the elderly. Although the pathogenesis of this disease remains still obscure, several researchers have report that death of retinal pigmented epithelium (RPE) caused by excessive accumulation of A2E is crucial determinants of AMD. In this study, the preventive effect of Vaccinium uliginosum L. (V.U) extract and its fractions on AMD was investigated in blue light-irradiated human RPE cell (ARPE-19 cells). Blue light-induced RPE cell death was significantly inhibited by the treatment of V.U extract or its fraction. To identify the mechanism, FAB-MS analysis revealed that V.U inhibits the photooxidation of N-retinyl-N-retinylidene ethanolamine (A2E) induced by blue light in cell free system. Moreover, monitoring by quantitative HPLC also revealed that V.U extract and its fractions reduced intracellular accumulation of A2E, suggesting that V.U extract and its fractions inhibit not only blue light-induced photooxidation, but also intracellular accumulation of A2E, resulting in RPE cell survival after blue light exposure. A2E-laden cell exposed to blue light induced apoptosis by increasing the cleaved form of caspase-3, Bax/Bcl-2. Additionally, V.U inhibited by the treatment of V.U extract or quercetin-3-O-arabinofuranoside. These results suggest that V.U extract and its fractions have preventive effect on blue light-induced damage in RPE cells and AMD.

We previously showed that Aster spathulifolius Maxim extract (ASE) reduced body weight gain and serum and liver lipid levels and significantly suppressed serum insulin and leptin concentrations in high-fat diet (HFD)-induced obese rats. Germacrone (GM) was identified as a potent bioactive constituent of ASE. In this study, we hypothesized that GM can attenuate hyperlipidemia by alleviating fatty acid (FA) synthesis/uptake and improve lipid metabolism by stimulating FA β-oxidation in HFD-induced obese C57BL/6J mice. To induce obesity, mice were fed an HFD for 6 weeks, while control mice were fed a commercial standard diet. The mice were allocated to six groups and fed either a normal diet, HFD, HFD with GM (5, 10, and 20 mg/kg), or HFD with 200 mg/kg Garcinia cambogia extract for 30 days. In the GM groups, body weight gain, visceral fat pad weight, fasting plasma glucose, serum insulin and leptin, and serum, as well as hepatic lipid, levels were attenuated. Transcriptional factors related to lipid metabolism, such as AMP-activated protein kinase α, sterol regulatory element-binding protein (SREBP) 1, SREBP 2, acetyl-CoA carboxylase, peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, FA synthase, and carnitine palmitoyltransferase 1, showed higher expression in the GM groups. In summary, GM may help attenuate hyperlipidemia by suppressing FA synthesis and uptake by inhibiting SREBP signaling pathway activation and improve lipid metabolism by stimulating FA β-oxidation by activating the AMPKα signaling pathway in HFD-induced obesity.

Our results suggest that GM may be a potent bioactive anti-adipogenic and lipolytic constituent via the regulation of adipogenesis, lipolysis and the AMPKα pathway.