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Monascus rice (MR) and highland barley monascus (HBM), the monascus fermented products, are applied in food and medicine to reduce cholesterol and promote digestion. Due to the fermentation substrates, their compositions are different. However, the exact differences have not been reported to date. By UPLC-Q-Orbitrap HRMS analysis, multiple components of twenty batches of MR and HBM samples were identified. In total, 100 components were confirmed ( e.g. , monacolins, pigments, decalin derivatives, amino acids). Then, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to filter the components of MR and HBM. In the PCA model, 88.1% of the total variance was uncovered. The OPLS-DA model showed better discrimination between MR and HBM, and the values of R 2 X , R 2 Y , and Q 2 were 0.837, 0.996, and 0.956, respectively. Based on the value of the variable importance in projection (VIP) and the result of the t -test, 424 components (VIP > 1, p < 0.05) were acquired. Finally, 11 differential components were selected as the characteristic compounds to discriminate between MR and HBM: the content of 9 monacolins (3-hydroxy-3,5-dihydrodehydromonacolin K, monacolin K, dehydromonacolin K, dehydromonacolin J hydroxy acid, monacophenyl, dihydromonacolin J hydroxy acid, monacolin L, dehydromonacolin J, and monacolin R) in HBM was higher than the content in MR, but the content of 2 pigments (ankaflavin and monascin) was lower in HBM and higher in MR. The findings revealed the similarities and differences in the chemical composition between MR and HBM, which is expected to provide a basis for quality control of HBM.

The mold Monascus has been used as a natural food coloring agent and food additive for more than 1000 years in Asian countries. In Chinese herbology, it was also used for easing digestion and antiseptic effects. Through a thorough investigation of a citrinin-free strain: M. purpureus BCRC 38110, four azaphilones, three benzenoids, one benzofuranone, one 5',6'-dihydrospiro[isochromane-1,2'-pyran]-4'(3' H )-one derivative, two steroids, and six tetralones have been successfully identified. Among them, monapyridine A (1), monatetralones A-E (2-6), and monabenzofuranone (7) were first reported. Their structures were characterized by 1D and 2D NMR, UV, IR, and HRESIMS analyses. With a series of bioactivity screening, monascuspirolide B (14) and ergosterol peroxide (16) exhibited concentration-dependent attenuation of the paclitaxel-induced neurite damage of mouse dorsal root ganglion neurons. The interleukin (IL)-1β-induced release of inflammatory cytokines IL-8 and tumor necrosis factor (TNF)-α in human chondrosarcoma cells was inhibited by monapurpureusone (8) and monascuspirolide B (14). Altogether, M. purpureus BCRC 38110 possessed potentials as natural therapeutics against inflammatory osteoarthritis and paclitaxel-induced neurotoxicity.

This study aimed to compare the hypolipidaemic activities of different Monascus pigments (yellow, red and orange pigments) and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in rats fed on a high-fat diet (HFD). Results showed that oral administrations of Monascus yellow, red and orange pigments can markedly alleviate the disturbance of lipid metabolism through ameliorating the serum lipid levels and suppressing hepatic lipid accumulation and steatosis. Meanwhile, the excretion of fecal cholesterol, triacylglycerols and bile acids was also promoted by the oral administrations of different Monascus pigments (MPs). Furthermore, Monascus pigment (MP) supplementation produced significant structural changes in the intestinal microbiota of HFD-fed rats, and modulated the relative abundance of functionally related microbial phylotypes compared with the HFD group in particular. Key phylotypes in response to the HFD and Monascus pigment (MP) intervention were found to strongly correlate with the lipid metabolism disorder associated parameters using Spearman's correlation coefficient. Some beneficial gut microbiota (such as Oscillibacter sp., Ruminococcus albus, Clostridium sp., etc.) were found to be negatively correlated with the serum and hepatic lipid indicator. Moreover, Monascus pigment (MP) treatments regulated the mRNA expression levels of the genes responsible for lipid and cholesterol metabolism. In general, different Monascus pigments (MPs) regulate the homeostasis of lipid and cholesterol metabolism through different regulatory pathways. These findings illustrated that not only Monascus yellow pigments, but also Monascus red and orange pigments have the potential to ameliorate lipid metabolic disorders, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperlipidemia and gut microbiota dysbiosis.

The metabolites of Monascus with multiple benefits are popular subjects for the development of functional foods. The yellow pigments, monascin and ankaflavin, which are the constituent metabolites of M. purpureus, M. pilosus and M. ruber, are becoming the focus of research on Monascus. Monascin and ankaflavin are azaphilone compounds with similar structures that exhibit multiple beneficial effects including anti-inflammation, anti-oxidation, anti-diabetes, immunomodulation, attenuation of Alzheimer's disease risk factor, and anti-tumorigenic effects. Monascin and ankaflavin not only possess pleiotropic bioactivities, but are also more potent than monacolin K in lowering lipid levels and have lower toxicity. Monascin and ankaflavin act as the activators of PPARγ agonist/Nrf-2 that subsequently ameliorate metabolic syndrome. Following the intensive exploration of Monascus bioactivities in recent years, the focus of research on Monascus-functional foods has shifted from whole fermented products/extracts to specific bioactive compounds. Therefore, the production of monascin and ankaflavin is an important topic with respect to Monascus-functional foods. Although several genomic studies have paved the way for understanding the production of secondary metabolites in Monascus, efforts are still required to effectively manipulate the biosynthesis of secondary metabolites with genetic engineering and/or culture techniques.

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 the anti-inflammatory pigments monascin and ankaflavin. Monascin has been shown to prevent or ameliorate several conditions, including hypercholesterolemia, hyperlipidemia, diabetes, and obesity. Recently, monascin has been shown to improve hyperglycemia, attenuate oxidative stress, inhibit insulin resistance, and suppress inflammatory cytokine production. In our recent study, we have found that monascin is a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist. The PPARgamma agonist activity had been investigated and its exerted benefits are inhibition of inflammation in methylglyoxal (MG)-treated rats, prevention of pancreas impairment causing advanced glycation endproducts (AGEs), promotion of insulin expression in vivo and in vitro, and attenuated carboxymethyllysine (CML)-induced hepatic stellate cell (HSC) activation in the past several years. Moreover, our studies also demonstrated that monascin also activated nuclear factor-erythroid 2-related factor 2 (Nrf2) in pancreatic RIN-m5F cell line thereby invading methylglyoxal induced pancreas dysfunction. In this review, we focus on the chemo-preventive properties of monascin against metabolic syndrome through PPARgamma and Nrf2 pathways.

Several lines of evidence have implicated high levels of advanced glycation endproducts (AGEs) in diabetes. Pancreas impairment caused by AGEs has been found in recent studies. Monascin (MS) and monacolin K (MK) are active compounds identified from Monascus-fermented products, which have been reported to inhibit inflammation and improve insulin resistance. In order to confirm the protective effects of MS and MK on pancreatic function, BALB/c mice were treated with AGEs via intraperitoneal injection for 22 weeks to induce hyperglycemia, and the pancreas-protecting mechanism of MS and MK from AGE-induced damage was investigated. We found that the expression of pancreatic and duodenal homeobox-1 (PDX-1) and glucose transporter 2 (GLUT2) was recovered by MS or MK administration to AGE-treated mice. In addition, MS strongly improved performance in the oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT), suggesting that MS sensitized to insulin in AGE-treated mice. Both MS and MK elevated pancreatic insulin expression when compared to the AGE-treated group, suggesting that MS and MK attenuated AGE-induced pancreatic dysfunction. Histopathology studies showed that intraperitoneal injection of AGEs did not result in pancreas damage. These findings confirm that the potential mechanism of AGEs on pancreatic dysfunction involves the induction of inflammation and the suppression of PDX-1 and GLUT2 expression. Taken together, MS and MK may be developed as an anti-diabetic agent in the future.

Monascin (MS) is a yellow compound isolated from Monascus-fermented products that has pancreatic protective, anti-inflammatory, anti-oxidative, and hypolipidemic activity. We recently found that MS also acts as a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, thereby promoting insulin sensitivity in C2C12 cells. However, the attenuation of hyperglycemia by MS treatment in vivo remains uncertain. In the present study, both MS and pioglitazone significantly down-regulated blood glucose and hyperinsulinemia in fructose-rich diet (FRD)-induced C57BL/6 mice (8 weeks). In addition, inhibitions of inflammatory factor production, serum dyslipidemia, and hepatic fatty acid accumulation by MS and pioglitazone were attenuated by GW9662 (PPARγ antagonist). These results were mediated by MS-suppressing FRD-elevated lipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), carbohydrate response element-binding protein (ChREBP), PPARγ coactivator-1α (PGC-1α), and PPARγ coactivator-1β (PGC-1β). Taken together, de novo lipogenesis results in hyperlipidemia and hyperglycemia by fructose induction thereby leading to diabetes development; we found that MS may inhibit lipogenesis in FRD-induced mice. These findings suggest that MS acts as an antidiabetic agent and thus may have therapeutic potential for prevention of diabetes.