ankaflavin and monascin

Monascus purpureus copiously yields beneficial secondary metabolites , including Monascus pigments, which are broadly used as food additives, as a nitrite substitute in meat products, and as a colorant in the food industry. Monascus yellow pigments (monascin and ankaflavin) have shown potential antidiabetic, antibacterial, anti-inflammatory, antidepressant, antibiotic, anticancer, and antiobesity activities. Cosmetic and textile industries are other areas where it has established its potential as a dye. This paper reviews the production methods of Monascus yellow pigments, biosynthesis of Monascus pigments from M. purpureus, factors affecting yellow pigment production during fermentation, and the pharmacological properties of monascin and ankaflavin.

Topics: Anti-Bacterial Agents; Fermentation; Flavins; Monascus; Pigments, Biological

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.

Topics: Animals; Fermentation; Flavins; Functional Food; Heterocyclic Compounds, 3-Ring; Humans; Metabolic Syndrome; Monascus

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.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Diabetes Mellitus; Flavins; Glycation End Products, Advanced; Heterocyclic Compounds, 3-Ring; Humans; Hypoglycemic Agents; Insulin; Liver; Monascus; NF-E2-Related Factor 2; Pancreas; PPAR gamma; Rats

Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Antioxidants; Central Nervous System Depressants; Ethanol; Flavins; Heterocyclic Compounds, 3-Ring; Lipid Metabolism; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; Monascus

Topics: Antioxidants; Flavins; Glycosylation; Heterocyclic Compounds, 3-Ring; Humans; Monascus; Serum Albumin, Human

Phytochemical investigation of the EtOAc-soluble fraction of the ethanolic extract of a yellow mutant of the fungus

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Benzopyrans; Ergosterol; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Monascus; Oryza; Pigments, Biological; RAW 264.7 Cells

Alcoholic hepatitis is a necroinflammatory process that is associated with fibrosis and leads to cirrhosis in 40% of cases. The hepatoprotective effects of red mold dioscorea (RMD) from Monascus purpureus NTU 568 were evaluated in vivo using a mouse model of chronic alcohol-induced liver disease (ALD).. ALD mice were orally administered vehicle (ALD group) or vehicle plus 307.5, 615.0 or 1537.5 mg kg. These results indicate the hepatoprotective effect of Monascus-fermented RMD. Moreover, AK and MS were identified as the active constituents of RMD for the first time and were shown to protect against ethanol-induced liver damage. © 2017 Society of Chemical Industry.

Topics: Animals; Dioscorea; Ethanol; Fermentation; Flavins; Hep G2 Cells; Heterocyclic Compounds, 3-Ring; Humans; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; Monascus; Plant Tubers; PPAR gamma; Protective Agents; Sterol Regulatory Element Binding Protein 1

Multireservoir nanocarriers were fabricated for delivering antineoplastic drug cocktail from herbal and fungal origin. Monascus yellow pigments (MYPs), monascin and ankaflavin, were isolated from red-mold rice, and incorporated within casein micelles (CAS MCs) along with the herbal drug, resveratrol (RSV). Both drugs (MYPs and RSV) were simultaneously incorporated into the hydrophobic core of CAS MCs. Alternatively, MYPs-loaded CAS MCs were enveloped within RSV-phytosomal bilayer elaborating multireservoir nanocarriers.. Cytotoxicity studies confirmed the superiority of multireservoir nanocarriers against MCF-7 breast cancer cells. The in vivo antitumor efficacy was revealed by reduction of the tumor volume and growth biomarkers.. Multireservoir CAS nanocarriers for codelivery of both MYPs and RSV may be promising alternative to traditional breast cancer therapy.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Caseins; Cell Survival; Drug Carriers; Drug Therapy, Combination; Female; Flavins; Heterocyclic Compounds, 3-Ring; Humans; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Mice, Inbred BALB C; Micelles; Monascus; Nanoparticles; Particle Size; Rats; Resveratrol

Monascin and ankaflavin, the major fractions of the fungal-derived monascus yellow pigments, were incorporated with the herbal drug, resveratrol (RSV) within the core of folate-conjugated casein micelles (FA-CAS MCs, F1) for active targeting. PEGylated RSV-phospholipid complex bilayer enveloping casein-loaded micelles (PEGPC-CAS MCs) were also developed as passive-targeted nanosystem.. FA- and PEGPC-CAS MCs demonstrated a proper size with monomodal distribution, sustained drug release profiles and good hemocompatibility. The coloaded MCs showed superior cytotoxicity to MCF-7 breast cancer cells compared with free drugs. Both nanosystems exerted excellent in vivo antitumor efficacy in breast cancer bearing mice with PEGylated MCs showing comparable tumor regression to folate-conjugated MCs.. Evergreen nanoplatforms coloaded with monascus yellow pigments and RSV were effective for breast cancer treatment.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Caseins; Drug Carriers; Female; Flavins; Folic Acid; Heterocyclic Compounds, 3-Ring; Humans; MCF-7 Cells; Mice; Micelles; Polyethylene Glycols; Polymers; Resveratrol; Xenograft Model Antitumor Assays

Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear.. This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism.. MS and AK lowered low-density lipoprotein cholesterol (LDL-C) and preserved high-density lipoprotein cholesterol contents. MS and AK inhibited acetyl-coenzyme A acetyltransferase, microsomal triglyceride transfer protein, and apolipoprotein (apo) B-100 expression, thereby preventing LDL assembly. In addition, enhanced LDL-receptor expression increased the transport of LDL-C to the liver for metabolism. MS and AK also significantly increase apo A1 expression, which facilitates high-density lipoprotein cholesterol formation.. Monascus-fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver.

Topics: Acetyl-CoA C-Acetyltransferase; Animals; Apolipoprotein A-I; Apolipoprotein B-100; Bile Acids and Salts; Body Weight; Carrier Proteins; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Eating; Feces; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Hypercholesterolemia; Lipids; Liver; Lovastatin; Male; Monascus; Rats

The influence of different illumination levels of blue light on the growth and intracellular pigment yields of Monascus strain M9 was investigated. Compared with darkness, constant exposure to blue light of 100 lux reduced the yields of six pigments, namely, rubropunctatamine (RUM), monascorubramine (MOM), rubropunctatin (RUN), monascorubrin (MON), monascin (MS), and ankaflavin (AK). However, exposure to varying levels of blue light had different effects on pigment production. Exposure to 100 lux of blue light once for 30 min/day and to 100 lux of blue light once and twice for 15 min/day could enhance RUM, MOM, MS, and AK production and reduce RUN and MON compared with non-exposure. Exposure to 100 lux twice for 30 min/day and to 200 lux once for 45 min/day decreased the RUM, MOM, MS, and AK yields and increased the RUN and MON. Meanwhile, the expression levels of pigment biosynthetic genes were analyzed by real-time quantitative PCR. Results indicated that gene MpPKS5, mppR1, mppA, mppB, mmpC, mppD, MpFasA, MpFasB, and mppF were positively correlated with the yields of RUN and MON, whereas mppE and mppR2 were associated with RUM, MOM, MS, and AK production.

Topics: Benzofurans; Benzopyrans; Flavins; Gene Expression; Genes, Fungal; Heterocyclic Compounds, 3-Ring; Light; Monascus; Pigments, Biological

Deep ocean water (DOW) obtained from a depth of more than 200 m includes abundant nutrients and minerals. DOW was proven to positively increase monascin (MS) and ankaflavin (AK) production and the anti-adipogenesis effect of Monascus-fermented red mold dioscorea (RMD). However, the influences that the major metals in DOW have on Monascus secondary metabolite biosynthesis and anti-adipogenesis remain unknown. Therefore, the major metals in DOW were used as the culture water to produce RMD. The secondary metabolites production and anti-adipogenesis effect of RMD cultured with various individual metal waters were investigated. In the results, the addition of water with Mg, Ca, Zn, and Fe increased MS and AK production and inhibited mycotoxin citrinin (CT). However, the positive influence may be contributed to the regulation of pigment biosynthesis. Furthermore, in the results of cell testing, higher lipogenesis inhibition was seen in the treatments of various ethanol extracts of RMD cultured with water containing Mg, K, Zn, and Fe than in those of RMD cultured with ultra-pure water. In conclusion, various individual metals resulted in different effects on MS and AK productions as well as the anti-adipogenesis effect of RMD, but the specific metals contained in DOW may cause synergistic or comprehensive effects that increase the significantly positive influence.

Topics: Adipogenesis; Citrinin; Dioscorea; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Lipogenesis; Metals; Monascus; Mycotoxins; Oceans and Seas; Seawater

The increased proliferation of activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and excessive extracellular matrix (ECM)-protein production. We examined the inhibitory effects of the Monascus purpureus-fermented metabolites, ankaflavin and monascin (15 and 30 μM), on the Akt/nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signaling pathways in HSC-T6 (activated hepatic stellate cell line). Ankaflavin and monascin (30 μM) induced apoptosis and significantly inhibited cell growth (cell viabilities: 80.2 ± 5.43% and 62.8 ± 8.20%, respectively, versus control cells; P < 0.05). Apoptosis and G1 phase arrest (G1 phase percentages: 76.1 ± 2.85% and 79.9 ± 1.80%, respectively, versus control cells 65.9 ± 4.94%; P < 0.05) correlated with increased p53 and p21 levels and caspase 3 activity and decreased cyclin D1 and Bcl-2-family protein levels (P < 0.05, all cases). The apoptotic effects of ankaflavin and monascin were HSC-T6-specific, suggesting their potential in treating liver fibrosis.

Topics: Animals; Apoptosis; Cell Proliferation; Cell Survival; Cells, Cultured; Down-Regulation; Flavins; Hepatic Stellate Cells; Heterocyclic Compounds, 3-Ring; Humans; Liver Cirrhosis; Male; Monascus; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Plant Extracts; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction

Monascus-fermented products have been used as dietary food and traditional medicine due to their beneficial effects on circulation and digestive systems in Asia for thousands of years. Besides, monascin and ankaflavin, secondary metabolites from Monascus-fermented products, have proven anti-inflammatory and immunomodulatory effects. In previous research, monascin and ankaflavin ameliorated ovalbumin-induced airway allergic reaction often used as a type I allergy asthma model. Additionally, mast cells play critical roles in type I allergy. Therefore, RBL-2H3 cells were used as the mast cell model to determine whether the improving effects on asthma of monascin and ankaflavin came from influencing mast cells. PMA and ionomycin are common activators of mast cells because they stimulate the main signaling molecules during mast cell activation. Forty micromolar monascin and ankaflavin inhibited PMA/ionomycin-induced mast cell degranulation and TNF-α secretion through suppressing the phosphorylation of PKC and MAPK family ERK, JNK, and p38. Consequently, monascin and ankaflavin affected the activation of mast cells and may have the potential to improve type I allergy.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Cell Line; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Humans; Mast Cells; Monascus; Oryza; Rats; Secondary Metabolism

Light is an important signal for fungi. We analyzed the influence of blue light of various intensities and illumination times on growth, monascin (MS) and ankaflavin (AK) biosyntheses in Monascus strain M9. Blue light changed the color of colonies. The colonies grown in the dark were orange, but turned pale when exposed to continuous blue light. MS production increased by 12.5, 27, and 14.5 % under blue light of 100 lux for 15 min/day, 100 lux for 30 min/day, and 200 lux for 15 min/day, respectively, compared to growth in the dark. AK production increased by 14.4, 22, and 13 % under the same condition. MS and AK production decreased when exposed to blue light of 300 and 450 lux. The expression of pigment biosynthetic genes were analyzed by real-time quantitative PCR and correlated with phenotypic production of MS and AK.

Topics: Biosynthetic Pathways; Flavins; Gene Expression Profiling; Heterocyclic Compounds, 3-Ring; Light; Monascus; Pigments, Biological

Yellow pigments monascin (MS) and ankaflavin (AK) are secondary metabolites derived from Monascus-fermented products. The hypolipidemic and anti-inflammatory effects of MS and AK indicate that they have potential on preventing or curing nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) and high-fat diet were used to induce steatosis in FL83B hepatocytes and NAFLD in mice, respectively. We found that both MS and AK prevented fatty acid accumulation in hepatocytes by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid beta-oxidation mediated by activating peroxisome proliferator-activated receptor (PPAR)-α and AMP-activated kinase (AMPK). Furthermore, MS and AK significantly attenuated high-fat diet-induced elevation of total cholesterol (TC), triaceylglycerol (TG), free fatty acid (FFA), and low density lipoprotein-cholesterol (LDL-C) in plasma. MS and AK promoted AMPK phosphorylation, suppressed the steatosis-related mRNA expression and inflammatory cytokines secretion, as well as upregulated farnesoid X receptor (FXR), peroxisome proliferator-activated receptor gamma co-activator (PGC)-1α, and PPARα expression to induce fatty acid oxidation in the liver of mice. We provided evidence that MS and AK act as PPARα agonists to upregulate AMPK activity and attenuate NAFLD. MS and AK may be supplied in food supplements or developed as functional foods to reduce the risk of diabetes and obesity.

Topics: Adenylate Kinase; Animals; Cytokines; Diet, High-Fat; Down-Regulation; Enzyme Activators; Fatty Liver; Flavins; Heterocyclic Compounds, 3-Ring; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; PPAR alpha; Real-Time Polymerase Chain Reaction

Deep ocean water (DOW) has, in previous studies, been found to be a novel anti-obesity drink and useful in raising Monascus-produced monascin and ankaflavin levels. This may resolve the limited anti-obesity ability of red mold dioscorea (RMD) known as the Monascus purpureus-fermented Disocorea batatas. This study aims to compare the anti-obesity effect of DOW-cultured RMD (DOW-RMD) and ultra-pure water-cultured RMD (UPW-RMD) in rats fed on a high fat diet. Moreover, the effect of ions composition of DOW and DOW-influenced functional metabolites change of RMD on the differentiation and lipogenesis regulation were investigated using 3T3-L1 pre-adipocytes. In the animal test, compared to UPW-RMD, DOW-RMD possessed better ability to inhibit increases in weight gain, and better feed efficiency, body-fat pad and cross-sectional area of adipocytes. In the cell test, the anti-obesity abilities of DOW-RMD in inhibiting PPARγ and C/EBPα expression in differentiation and lipoprotein lipase activity in lipogenesis were contributed to by the DOW-increased monascin and ankaflavin levels and the ions of DOW, respectively.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Dioscorea; Fermentation; Flavins; Fungi; Heterocyclic Compounds, 3-Ring; Lipids; Male; Monascus; Obesity; Rats; Rats, Sprague-Dawley; Seawater; Water

Monacolin K has long been considered a major effective component in the hypolipidemic functions of Monascus . Monacolin K also serves as a well-known hypolipidemic medication, but its side effect myopathy is a concern. Monascin and ankaflavin, the yellow pigments produced by Monascus species, have been proven to possess hypolipidemic functions; however, no studies have compared the hypolipidemic effects of monascin, ankaflavin, and monacolin K under the same dosages. In this study, the equal dosages of monascin, ankaflavin, and monacolin K were oral administrated to hamsters fed a high cholesterol diet for 6 weeks. Comparison of the displayed hypolipidemic and anti-atherosclerosis effects was performed, in addition to an investigation into the inducement of side effect. The results indicated that monascin and ankaflavin were similar to monacolin K in significantly reducing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels in serum and lipid plaque (p < 0.05) in the heart aorta. In addition, ankaflavin achieved the effects of serum TC and TG reduction, with no significant difference as compared to those effects of monacolin K (p > 0.05). However, as compared to monacolin K, ankaflavin possessed more significant effects on the prevention of fatty liver and lipid plaque accumulation in heart aorta. More importantly, monascin significantly enhanced high-density lipoprotein cholesterol (HDL-C) concentrations, while monacolin K displayed the opposite effect. Regarding the side effect, monacolin K also raised elevated creatinine phosphokinase (CPK) activity, which was highly correlated with rhabdomyolysis development, while monascin and ankaflavin did not induce such a side effect. In conclusion, MS and AK had the potential to be developed as hypolipidemic agents without rhabdomyolysis development.

Topics: Animals; Aorta; Atherosclerosis; Creatine Kinase; Cricetinae; Flavins; Heterocyclic Compounds, 3-Ring; Lipid Peroxidation; Lipids; Liver Function Tests; Lovastatin; Male; Mesocricetus

Monascus-fermented monascin and ankaflavin are found to strongly inhibit differentiation and lipogenesis and stimulate lipolysis effects in a 3T3-L1 preadipocyte model, but the in vivo regulation mechanism is unclear. This study uses obese rats caused by a high-fat diet to examine the effects of daily monascin and ankaflavin feeding (8 weeks) on antiobesity effects and modulation of differentiation, lipogenesis, and lipid absorption. The results show that monascin and ankaflavin had a significant antiobesity effect, which should result from the modulation of monascin and ankaflavin on the inhibition of differentiation by inhibiting CCAT/enhancer-binding protein β (C/EBPβ) expression (36.4% and 48.3%) and its downstream peroxisome proliferator-activated receptor γ (PPARγ) (55.6% and 64.5%) and CCAT/enhancer-binding protein α (C/EBPα) expressions (25.2% and 33.2%) and the inhibition of lipogenesis by increasing lipase activity (14.0% and 10.7%) and decreasing heparin releasable lipoprotein lipase (HR-LPL) activity (34.8% and 30.5%). Furthermore, monascin and ankaflavin are the first agents found to suppress Niemann-Pick C1 Like 1 (NPC1L1) protein expression (73.6% and 26.1%) associated with small intestine tissue lipid absorption. Importantly, monascin and ankaflavin are not like monacolin K, which increases creatine phosphokinase (CPK) activity, known as a rhabdomyolysis indicator.

Topics: Adipocytes; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Creatine Kinase; Diet, High-Fat; Dose-Response Relationship, Drug; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Lipogenesis; Lipolysis; Lovastatin; Male; Membrane Transport Proteins; Monascus; Obesity; PPAR gamma; Rats; Rats, Sprague-Dawley

Previous studies have established that red mold rice can regulate blood pressure in spontaneously hypertensive rats (SHR) and that Monascus -fermented products, including monacolin K, ankaflavin (AF), and monascin (MS), can inhibit expression of adhesion factors such as E-selectin and endothelin-1 to prevent human acute monocytic leukemia cell line THP-1 monocytes from adhering to human aortic endothelial cells. However, it remains unknown whether AF and MS act directly on human umbilical endothelial cells (HUVECs) to enhance nitric oxide (NO) synthesis through the stimulation of endothelial NO synthase (eNOS) expression. To address this knowledge gap, this study investigated whether AF and MS directly regulate NO synthesis and attenuate adhesion factor expression induced by treatment with tumor necrosis factor-α (TNF-α) in HUVECs. The results revealed that both AF and MS (20 μM) treatments promoted increases in eNOS expression and decreases in vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and endothelin-1 mRNA and protein expression resulting from 12 h of TNF-α treatment. These effects are attributed to the ability of AF and MS to inhibit extracellular signal-regulated protein kinase (ERK) phosphorylation and nuclear factor κB (NF-κB) translocation from the cytoplasm into the nucleus, thereby exerting antihypertensive activity.

Topics: Cell Adhesion Molecules; Cell Cycle; Cell Survival; E-Selectin; Endothelin-1; Flavins; Gene Expression; Heterocyclic Compounds, 3-Ring; Human Umbilical Vein Endothelial Cells; Humans; Nitric Oxide Synthase Type III; Tumor Necrosis Factor-alpha

Inflammation is an independent risk factor of cardiovascular diseases and is associated with endothelial dysfunction. Monascus purpureus-fermented rice, containing naturally occurring statins and various pigments, has lipid-modulating, anti-inflammatory and antioxidative effects.. The effects of monacolin K, ankaflavin and monascin, as metabolites from Monascus-fermented rice, on the expression of cell adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecular-1 (VCAM-1) and E-selectin) by tumor necrosis factor (TNF)-α-treated human aortic endothelial cells (HAECs) were investigated. Supplement of HAECs with these Monascus-fermented rice metabolites significantly suppressed cellular binding between the human monocytic cells U937 and TNF-α-stimulated HAECs. Immunoblot analysis showed that Monascus-fermented rice metabolites significantly attenuated TNF-α-induced VCAM-1 and E-selectin but not ICAM-1 protein expression. Gel shift assays showed that Monascus-fermented rice metabolites treatment reduced TNF-α-activated transcription factor nuclear factor (NF)-κB. Furthermore, Monascus-fermented rice metabolites also attenuated reactive oxygen species (ROS) generation in vitro and in TNF-α-treated HAECs. Supplement with an ROS scavenger N-acetylcysteine gave similar results as compared with Monascus-fermented rice metabolites.. Monascus-fermented rice metabolites reduced TNF-α-stimulated endothelial adhesiveness as well as downregulating intracellular ROS formation, NF-κB activation, and VCAM-1/E-selectin expression in HAECs, supporting the notion that the various metabolites from Monascus-fermented rice might have potential implications in clinical atherosclerosis disease.

Topics: Acetylcysteine; Aorta; Cell Adhesion; Cell Line; E-Selectin; Endothelial Cells; Fermentation; Flavins; Heterocyclic Compounds, 3-Ring; Humans; Lovastatin; Monascus; NF-kappa B; Oryza; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

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

One new tetralone, monaspurpurone (1), was isolated from the EtOH extract of a yellow mutant of the fungus Monascus purpureus BCRC 38113 (Eurotiaceae) grown on rice, along with five known compounds, β-sitosteryl palmitate (2), ergosterol (3), ankaflavin (4), monascin (5) and p-nitrophenol (6). They were characterised on the basis of spectral analysis and comparison with literature data. All the isolates were also evaluated for the scavenging properties towards the DPPH in TLC autographic and spectroscopic assays.

Topics: Biphenyl Compounds; Chromatography, Thin Layer; Ergosterol; Flavins; Free Radical Scavengers; Heterocyclic Compounds, 3-Ring; Molecular Structure; Monascus; Nitrophenols; Oryza; Palmitates; Picrates; Sitosterols; Spectrum Analysis; Tetralones

Monascus-fermented red mold dioscorea (RMD) has been proven to possess greater hypolipidemic effect than red mold rice (RMR) even though they include equal levels of cholesterol-lowering agent monacolin K. However, higher concentrations of yellow pigments (monascin and ankaflavin) were found in RMD than in RMR. In this study, purified monascin and ankaflavin were administered to hyperlipidemic hamsters for 8 weeks, respectively, to test whether these two compounds were novel hypolipidemic ingredients. In the statistical results, monascin and ankaflavin showed significant effect on lowering cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in serum, as well as aorta lipid plaque (p < 0.05). Importantly, monascin and ankaflavin, unlike monacolin K, were able to perform up-regulation rather than down-regulation on high-density lipoprotein cholesterol (HDL-C) levels in serum. This finding not only explained why RMD showed greater hypolipidemic and HDL-C-raising effect than RMR but also proved that monascin and ankaflavin would act as novel and potent hypolipidemic ingredients.

Topics: Animals; Basal Metabolism; Bone Density; Cholesterol, HDL; Cricetinae; Dioscorea; Flavins; Heterocyclic Compounds, 3-Ring; Hypolipidemic Agents; Lipid Peroxidation; Male; Mesocricetus

The aim of the present work is to investigate the effects of Monascus secondary metabolites, monascin (MS) and ankaflavin (AK), on cell proliferation, adipogenesis, lipolysis and heparin-releasable lipoprotein lipase (HR-LPL) in 3T3-L1 preadipocyte. MS and AK inhibit the proliferation of 3T3-L1 cells in a dose-dependent fashion. At 8 μg/mL concentration MS inhibits proliferation for 80.5% after 48 h, whereas the value for AK is 69.2%. Adipogenesis is inhibited by MS and AK without dose-dependency. Triglyceride is decreased 37.1% and 41.1% respectively by treating 0.125 μg/mL MS and AK. Adipocyte-specific transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein β (C/EBPβ), C/EBPδ and C/EBPα mRNA levels are measured by real-time polymerase chain reaction. The expression of the four transcriptional factors analyzed (PPARγ, C/EBPβ, C/EBPδ and C/EBPα) is reduced at the initial and the middle period. At the later period, there is no effect on the expression of PPARγ and C/EBPα by treating MS and AK. Furthermore, both MS and AK increase basal lipolysis of mature adipocytes by 113.2% and 278.3% upregulation, respectively. And both MS and AK reduce the activity of HR-LPL, by 45.3% and 58.1% reduction, respectively. This study reveals for the first time that Monascus secondary metabolites, MS and AK, can prevent the differentiation of preadipocyte and stimulate basal lipolysis of mature adipocytes, avoiding the accumulation of lipid.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Flavins; Heterocyclic Compounds, 3-Ring; Lipolysis; Lipoprotein Lipase; Macrolides; Mice; Monascus