Peanut sprouts have shown promise in protecting against obesity and hyperlipemia, but their potentials in hyperglycemia management remains unknown. The aim of this study was to investigate the effects and possible mechanisms of peanut sprout on experimental hyperglycemia. To do so, C57BL/6 male mice were fed a chow diet or high-fat-diet for 8 weeks to induce obesity, and then were given in addition either vehicle or peanut sprout extracts (PSE, 100, 300 and 1000 mg/kg/day) by oral gavage for an additional 6 weeks. Data showed that PSE treatment effectively protected against weight gain, reduced hepatic steatosis and improved hyperglycemia in mice. Using an LC-MS/MS approach, we discovered that PSE contains substantial amounts of resveratrol (RES), piceatannol (PIC), caffeic acid (CA), indole-3-acetic acid (IAA) and tryptophan (Trp). On the basis of bioassay-guided fractionation, we identified IAA as its major active principle suppressing hepatic gluconeogenesis in primary hepatocytes. When administered chronically to mice with diet-induced obesity, IAA effectively improved experimental hyperglycemia in a dose-dependent manner. Mechanistically, we demonstrated that 3-IAA could directly antagonize the action of glucagon, abrogate the phosphorylation of CREB and nuclear translocation of CRTC2, lower the protein expression of key gluconeogenic enzymes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1), and thus normalize glucagon-dependent glucose output. Taken together, peanut sprouts might have implications for novel nutrition-based preventive or adjuvant therapeutic strategies against hyperglycemia.

Loss of susceptibility to anoikis signals is a crucial step in metastasis. Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management. In this study, we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods. Among 19 tested dietary phytochemicals, the best results were obtained with apigenin, a natural component of celery. Phenotypically, apigenin sensitized breast cancer cells to anoikis, lowered the number of circulating tumor cells, and protected against breast cancer metastasis to lung in mice. Mechanistically, we demonstrated that the thromboxane A₂ (TXA₂)-TXA₂ receptor (TP) axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway. Blockage of TXA₂ signaling up-regulated p53 as well as its target gene p21, caused a G1 phase arrest, and finally led to apoptosis in breast cancer cells. TXA₂ level was positively correlated with breast cancer cell anoikis rate, and apigenin significantly inhibited TXA₂ biosynthesis in vitro and in vivo. Collectively, we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer, and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.