Diets high in fat lead to excessive lipid accumulation in adipose tissue, which is a crucial factor in the development of obesity, hepatitis, and hyperlipidemia. In this study, we investigated the antiobesity effect of a flavonoid-enriched extract from Nelumbo nucifera leaf (NLFE) in vivo. C57BL/6 mice were fed with a high-fat diet (HFD) to induce obesity. NLFE reduced the body weight, body lipid accumulation, and activities of fatty acid synthase (FAS), glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. NLFE also suppressed the expression of FAS, acetyl-CoA carboxylase, and HMGCoA reductase and increased the phosphorylation of AMP-activated protein kinase in the liver. Taken together, we demonstrated that NLFE targets lipid-regulated enzymes and may be effective in attenuating body lipid accumulation and preventing obesity.

Gallic acid (GA), 3,4,5-trihydroxybenzoic acid, is a natural polyphenolic acid and widely found in gallnuts, tea leaves and various fruits. Previous studies have shown that GA possesses anti-inflammatory, antiallergic and anticarcinogenic activity. In the present study, we aim to investigate the antitumor effects of GA on breast cancer cell. Our results revealed that GA treatment significantly reduced the cell growth of human breast cancer cell MCF-7 in a dose-dependent manner. Further flow cytometric analysis showed that GA induced significant G2/M phase arrest but slightly affected the population of sub-G1MCF-7 cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, CDK2, cyclin B1 and cdc2/CDK1 were diminished; in contrast, levels of the negative regulators p27(Kip1) and p21(Cip1) were increased by GA treatment. Additionally, Skp2, a specific ubiquitin E3 ligase for polyubiquitination of p27(Kip1) was reduced by GA treatment. Further investigation showed that GA attenuated Skp2-p27(Kip1) association and diminished polyubiquitination of p27(Kip1) in MCF-7 cells. Moreover, knockdown of p27(Kip1) but not p21(Cip1) significantly alleviated GA-induced accumulation of G2/M phase. These findings indicate that GA may upregulate p27(Kip1) level via disruption of p27(Kip1)/Skp2 association and the consequent degradation of p27(Kip1) by proteosome, leading to G2/M phase arrest of MCF-7 cell. It is suggested that GA should be beneficial to treatment of breast cancer and p27(Kip1)-deficient carcinomas.

Our study suggests that the hypolipidemic effects of MWE occur via phosphorylation of AMPK and inhibition of lipid biosynthesis. Therefore, the mulberry extract may be active in the prevention of fatty liver.

This study investigated the influence of phenolic caffeic acid on obesity in mice fed a high fat diet and its underlying mechanisms base on adipose and hepatic lipid lipogenesis. C57BL/6 mice were fed a normal diet or a HFD (20% fat, w/w) with or without caffeic acid (0.02% and 0.08%, w/w) for 6 weeks. The effects of caffeic acid on hyperlipidemia, hyperglycemia, visceral fat accumulation, and related enzyme activities in HFD-mice are examined. The supplementation of caffeic acid significantly lowered body weight, visceral fat mass, plasma GOT and GPT levels, FAS activity, and free fatty acid compared to the HFD group. Caffeic acid also lowered triglyceride and cholesterol concentrations in plasma and liver. Furthermore, we showed that caffeic acid efficiently inhibited cholesterol biosynthesis as evidenced by 3-hydroxy-3-methylglutaryl CoA reductase in the liver. Caffeic acid supplementation suppressed the activity of lipogenesis via sterol regulatory element-binding protein 1 c and its target enzyme fatty acid synthase. In addition, caffeic acid resulted in increased phosphorylation of AMP-activated protein kinase and decreased acetyl carboxylase, a downstream target of AMPK, which are related to fatty acid β-oxidation in the liver. In conclusion, these results indicate that caffeic acid exhibits a significant potential as an antiobesity agent by suppression of lipogenic enzymes and hepatic lipid accumulation.

Mulberry (桑葚子 sāng shèn zǐ), a traditional Chinese medicine (TCM) in Taiwan, has many bioactive substances, including polyphenol and anthocyanins compounds. Over the past decade, many scientific and medical studies have examined mulberry fruit for its antioxidation and antiinflammation effects both in vitro and in vivo. This review thus focuses on the recent advances of mulberry extracts (MEs) and their applications in the prevention and treatment of human cancer, liver disease, obesity, diabetes, and cardiovascular disease. The ME modulates several apoptotic pathways and matrix metalloproteinases (MMPs) to block cancer progression. Mulberry can increase detoxicated and antioxidant enzyme activities and regulate the lipid metabolism to treat hepatic disease resulting from alcohol consumption, high fat diet, lipopolysaccharides (LPS) and CCl4 exposure. Of the various compounds in ME, cyanidin 3-glucoside (C3G) is the most abundant, and the active compound studied in mulberry research. Herein, the antioxidant and antiinflammatory actions of C3G to improve diabetes and cardiovascular disease are also discussed. These studies provide strong evidence ME may possess the bioactivity to affect the pathogenesis of several chronic diseases.