Treatment of metabolic syndrome with ankaflavin, a secondary metabolite isolated from the edible fungus Monascus spp.

Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number of functional secondary metabolites, including anti-inflammatory pigments (such as monascin and ankaflavin [AK]), monacolins, and dimerumic acid. These secondary metabolites have anti-inflammatory, anti-oxidative, and anti-tumor activities. We found that AK positively regulates several transcription factors associated with the prevention of metabolic syndrome and other diseases, including peroxisome proliferator-activated receptor (PPAR)-gamma, PPAR-alpha, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AK reduced hyperglycemia and enhanced pancreatic function via PPAR-gamma activation and increased lipid metabolism due to PPAR-alpha activation. The compound also exerted antioxidant effects via activation of Nrf2. These results suggest that AK belongs to the class of selective peroxisome proliferator-activated receptor modulators (SPPARMs), which are associated with a good safety profile when used in patients suffering from metabolic syndrome. Together with our studies to determine how AK production can be increased during Monascus fermentation, these data demonstrate the great potential of AK as a nutraceutical or therapeutic agent.