ankaflavin and Disease-Models--Animal

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.

Topics: Animals; Disease Models, Animal; Flavins; Metabolic Syndrome; Monascus; Pigments, Biological; PPAR alpha; Treatment Outcome

It is well-known that steatotic liver is more susceptible to ischemia-reperfusion (I/R) injury during liver transplantation, liver resection and other liver surgeries. The increasing incidence of non-alcoholic fatty liver disease (NAFLD) decreases the availability of liver donors. Although steatotic liver is now accepted as a source of liver for transplantation, NAFLD exacerbates the liver injury after liver surgery. The present study was to investigate the protective role of ankaflavin in steatotic liver I/R injury.. The model of fatty liver mice was induced with high fat diet in four weeks, ankaflavin or vehicle (saline) was administrated by gavage once a day for one week. The animals were subjected to partial hepatic I/R. Blood samples were collected to measure serum aminotransferases. The liver tissues were used to examine liver steatosis, apoptosis of hepatocytes, hepatic oxidative stress, Kupffer cells and inflammatory cytokines. The effects of ankaflavin on inflammatory cytokines were evaluated in isolated Kupffer cells from the steatotic liver.. Ankaflavin reduced liver steatosis in high fat diet mice. Compared with normal mice, I/R induced more damage to the mice with steatosis, such as hepatocyte apoptosis, inflammatory cytokines (TNF-alpha, IL-6 and IL-1 beta), serum aminotransferases and thiobarbituric acid reactive substances. Importantly, ankaflavin administration significantly attenuated these changes. In addition, ankaflavin significantly decreased the proliferation of Kupffer cells and the expression of TNF-alpha, IL-6 and IL-1 beta protein in isolated Kupffer cells stimulated by TNF-alpha.. Ankaflavin has protective effects against I/R injury through anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms in fatty livers, these effects are at least partially mediated by inhibiting Kupffer cell functions.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Cell Proliferation; Cytokines; Cytoprotection; Disease Models, Animal; Flavins; Hepatocytes; Kupffer Cells; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Reperfusion Injury

This experiment established the ovariectomized (OVX) rat model of postmenopausal osteoporosis and examined the effect of the oral administration of different dosages of dioscorea, red mold dioscorea (RMD), and soy isoflavones on bone mineral density (BMD). Three months after osteoporosis had been induced and 4 weeks after feeding had begun, the tibia and femur BMD of OVX rats administered RMD showed significant increases compared with that of all other groups of OVX rats. Closer examination using microcomputed tomography also revealed that the RMD-administered rats had denser trabecular bone volume and a higher trabecular number compared to all other rat groups. Reconstructed 3D imaging indicated increases in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in OVX rats. These findings indicate that administration of monacolin K and phytoestrogen diosgenin could prevent bone loss induced by estrogen deficiency.

Topics: Animals; Bone Density; Dioscorea; Diosgenin; Disease Models, Animal; Female; Fermentation; Flavins; Glycine max; Heterocyclic Compounds, 3-Ring; Isoflavones; Lovastatin; Monascus; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Roots; Rats; Rats, Sprague-Dawley