Monascus-fermented grain vinegar enhances glucose homeostasis through the IRS-1/PI3K/Akt and AMPK signaling pathways in HepG2 cell and db/db mice.

MV was reported to have beneficial effects in ameliorating insulin resistance in db/db mice, but the intrinsic mechanisms for glucose homeostasis are unclear. This study examined the anti-diabetic mechanism of MV using HepG2 cells and C57BL/KsJ-db/db mice. MV increased insulin sensitivity by promoting insulin-dependent glucose uptake and activating glycogen accumulation in HepG2 cells. Furthermore, the glucose homeostasis was enhanced in db/db mice administered 1 mg/kg/day of MV for eight weeks by activating the IRS-1/PI3K/Akt and AMPK pathways in the skeletal muscle and liver tissue. In addition, MV promoted glycogen synthesis by regulating the key enzymes, including GSK-3ß and GS, and suppressed gluconeogenesis by inhibiting the mRNA expressions of G6pase and PEPCK. These findings show that MV regulates both signaling pathways and improves the glucose metabolism disorder. Thus, MV might be an alternative functional food or nutraceutical in ameliorating T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01146-4.

Hypoglycemic and Hypolipogenic Action of Acetic Acid and Monascus-Fermented Grain Vinegar: A Comparative Study.

Acetic acid has been proposed to improve lifestyle-related diseases, including hyperlipidemia and hyperglycemia. This study compared the hypoglycemic and hypolipogenic effects of acetic acid vinegar (AV, contains only 4% acetic acid) and Monascus-fermented grain vinegar (MV) containing various bioactive compounds in 3T3L1 cells and C57BL/KsJ-db/db mice (DB). The DB were divided randomly into three treatment groups containing nine mice each; DB-, AV-, and MV-groups were orally administered 1 mL/kg/day of distilled water, acetic acid vinegar, and Monascus vinegar, respectively, for 8 weeks. Exposure to AV and MV inhibited the adipogenic differentiation of 3T3L1 preadipocytes and lipid accumulation during differentiation. Oral administration of AV or MV to the mice resulted in a marked reduction in the body weight, liver weight, and hepatic triglyceride content compared to the control DB-group. Moreover, treatment with AV and MV clearly increased the expression of cyclic adenosine monophosphate (cAMP) and AMP-activated protein kinase (AMPK) and suppressed the expression of fatty acid synthetase in liver tissues of DB. Significantly, lower levels of fasting blood glucose, insulin, leptin, and the glycosylated hemoglobin (HbA1c) as well as higher levels of the skeletal muscle GLUT4 expression were obtained in the AV- or MV-groups than levels determined in the control DB-group (P < .05). Although MV has the potential to be a natural alternative treatment for obesity-associated type 2 diabetes, this study suggests that acetic acid is the central ingredient in MV responsible for the hypoglycemic and hypolipogenic effects in the DB mice.

In Vitro Inhibitory Effects of Organic Acids Identified in Commercial Vinegars on α-Amylase and α-Glucosidase.

The aim of this work was to evaluate the inhibitory activities of organic acids identified from commercial vinegars on α-amylase and α-glucosidase. Six organic acids (acetic, citric, lactic, malic, succinic, and tartaric) were identified in nine commercial vinegars, whose contents varied considerably depending on the raw materials. Most of the fruit vinegars, comprised of various organic acids, were found to be more effective inhibitors against digestive enzymes than grain vinegars containing mainly acetic acid. Citric acid had the lowest IC50 values for α-amylase and α-glucosidase activities 0.64±0.04 µM/mL and 8.95±0.05 µM/mL, respectively, and thus exhibited the strongest antidiabetic effect. Mulberry fruit vinegar containing the highest content of total organic acid (111.02±1.50 mg/mL) showed the strongest digestive enzyme inhibitory impact. The results indicate that vinegars with higher contents of various organic acids hold strong potential against digestive enzymes.

Hypouricemic and Antioxidant Effects of Soy Vinegar Extracts in Hyperuricemic Mice.

We investigated the potential hypouricemic and antioxidant activities of soy vinegar brewed from soybeans fermented with Monascus pilosus KCCM 60084 in potassium oxonate-induced hyperuricemic mice. Soy vinegar extracts (SVEs), which contain free isoflavones, ubiquinones, γ-aminobutyric acid, gallic acid, and acetic acid, reduced the level of uric acid (UA) by decreasing UA production through xanthine oxidase inhibition and increasing UA excretion through uricase activity in hyperuricemic mice (P < .05). Moreover, SVE administration increased hepatic antioxidant enzyme activities in a dose-dependent manner. The results suggest that soy vinegar has potential with natural ingredients to prevent and treat hyperuricemia.

Effect of Monascus-Fermented Soybean Extracts on Antioxidant and Skin Aging-Related Enzymes Inhibitory Activities.

We investigated the in vitro inhibitory activity against skin aging-related enzymes and antioxidant activity of Monascus-fermented soybean extracts (MFSEs) obtained by using different solvents. The highest Trolox equivalent (TE) antioxidant capacity (3.13±0.06 mM TE/g) and oxygen radical absorbance capacity (2.79±0.09 mM TE/g) of MFSEs were evaluated for the methanol and 80% ethanol extracts, respectively. The antioxidant capacities increased with increasing concentration (0.5~50 mg/mL). In addition, the methanol and 80% ethanol extracts showed an effective inhibition against tyrosinase, hyaluronidase, and elastase compared with those of acetone and hot water extracts (P<0.05). Results indicate that the inhibitory activities against skin aging-related enzymes and antioxidant properties provide evidence for the nutricosmetic potentials of Monascus-fermented soybeans.

Monascus-mediated fermentation improves the nutricosmetic potentials of soybeans.

The potential nutricosmetic activities and compositional changes of 80% ethanol extracts of white soybean (MFWS) and black soybean (MFBS) fermented with Monascus pilosus KCCM 60084 at 30°C for 30 days were investigated. Monascus-fermented soybean extracts (MFSEs) showed stronger nutricosmetic potentials in terms of antioxidant as well as tyrosinase and elastase inhibitory activities compared to those of unfermented soybean extracts (p<0.05). Extracts (50mg/mL) from MFBS inhibited the α-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in B16F10 cells more potently than arbutin. HPLC/MS analysis demonstrated that aglycone isoflavones and coenzyme Q10 (CoQ10) levels increased about 33.4- and 3.0-fold in the MFSEs after 20 days of fermentation, respectively. A linear correlation (r 2=0.67 to 0.99) between nutricosmetic activity and concentrations of CoQ10, genistein, and daidzein, which are commonly associated with nutraceutical effects, was observed. Results indicate that Monascus-mediated fermentation can be an efficient strategy to improve nutricosmetic functionality of soybeans.

Comparison of the effects of blending and juicing on the phytochemicals contents and antioxidant capacity of typical korean kernel fruit juices.

Four Korean kernel fruit (apple, pear, persimmon, and mandarin orange) juices were obtained by household processing techniques (i.e., blending, juicing). Whole and flesh fractions of each fruit were extracted by a blender or a juicer and then examined for phytochemical content (i.e., organic acids, polyphenol compounds). The antioxidant capacity of each juice was determined by ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Results revealed that juices that had been prepared by blending whole fruits had stronger antioxidant activities and contained larger amounts of phenolic compounds than juices that had been prepared by juicing the flesh fraction of the fruit. However, the concentration of ascorbic acid in apple, pear, and mandarin orange juices was significantly (P<0.05) higher in juice that had been processed by juicing, rather than blending. The juices with the highest ascorbic acid (233.9 mg/serving), total polyphenols (862.3 mg gallic acid equivalents/serving), and flavonoids (295.1 mg quercetin equivalents/serving) concentrations were blended persimmon juice, blended mandarin orange juice, and juiced apple juice, respectively. These results indicate that juice extraction techniques significantly (P<0.05) influences the phytochemical levels and antioxidant capacity of fruit juices.

Preventive effect of Monascus-fermented products enriched with ubiquinones on type 2 diabetic rats induced by a high-fructose plus high-fat diet.

The aim of the present study was to investigate whether the aqueous extract of Monascus-fermented grains (MFGEs) enriched with ubiquinones (Coenzyme Qs, CoQ9+CoQ10) alleviates high-fructose (60%) plus high-fat (20%) diet (HFD)-induced hyperglycemia and hepatic oxidative stress in male Sprague-Dawley rats. Animals were fed HFD for 16 weeks and orally administered with MFGEs (300 mg/kg/day) or atorvastatin (20 mg/kg/day) for the last 4 weeks of the study. HFD-fed rats exhibited hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and impaired insulin sensitivity. MFGE treatment prevented the increase in glucose levels and index of insulin resistance in the HFD-induced diabetic rats. A significant decrease in hepatic lipid peroxidation and significant increases in hepatic superoxide dismutase, catalase, and glutathione peroxidase were observed in the MFGE supplemented group. The results suggest that dietary supplementation with MFGEs enriched with CoQs exerts an antidiabetic effect in type 2 diabetic rats by improving insulin resistance and hepatic antioxidant enzymes.

Effects of Monascus-fermented grain extracts on plasma antioxidant status and tissue levels of ubiquinones and α-tocopherol in hyperlipidemic rats.

We investigated the effects of Monascus-fermented mixed grain extracts (MFGEs) enriched with bioactive mevinolins (natural statins) and coenzyme Qs (CoQ9+CoQ10) on the blood lipids, antioxidant status, and tissue levels of CoQs and α-tocopherol (α-Toc) in hyperlipidemic rats. The oral administration of MFGEs (300 mg/kg body weight per day) for 8 weeks resulted in a significant decrease in blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio compared to the control and lovastatin supplement group of a dosage of 20mg/kg per day (p<0.05). Furthermore, a significant increase in the ratios of α-Toc/LDL-C and CoQs/LDL-C in plasma and tissues and improvement in plasma antioxidant status as measured by TBARS and TRAP were observed in hypercholesterolemic rats (p<0.05). Regarding the effects of MFGEs on antioxidant levels of plasma and tissues, there were significant increases in the levels of α-Toc (p<0.05) and CoQs (p<0.01) after the 8-week MFGEs treatment. These data indicate that MFGEs supplementation not only decreases blood lipids and lipid peroxidation but also increases levels of antioxidants such as α-Toc and CoQs and may improve plasma antioxidant status as well as a hypolipidemic effect.

Hypolipidemic effects of Monascus-fermented soybean extracts in rats fed a high-fat and -cholesterol diet.

We evaluated whether Monascus-fermented soybean extracts (MFSE) enriched with bioactive mevinolins (natural statins) and aglycone isoflavones (daidzein, glycitein, and genistein) perform an additive hypolipidemic effect in hyperlipidemic rats than unfermented soybean extracts (UFSE), which have a higher level of glucoside isoflavones (daidzin, glycitin, and genistin) without mevinolin. The oral administration of MFSE (200 and 400 mg kg(-1) body weight) significantly lowered the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels (p < 0.01) and raised high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05) in hyperlipidemic rats. The MFSE group had a significantly lower 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity and higher atherogenic index (calculated as HDL-C/LDL-C) when compared with the UFSE group (400 mg kg(-1) body weight) (p < 0.05). Treatment with both MFSE200 and MFSE400 groups for 40 days significantly reduced the activities of serum aspartate aminotransferase and alanine aminotransferase by averages of 35.6 and 43.2%, respectively, as compared to the high-fat diet group (p < 0.01). The results indicate that MFSE performs a more potent hypolipidemic action via improvement of the lipid profiles and down-regulated HMG-CoA reductase activity than UFSE in hyperlipidemic rats.

Physicochemical and sensory characteristics of a medicinal soy yogurt containing health-benefit ingredients.

Medicinal soy yogurt (sogurt) containing high levels of gamma-aminobutyric acid (GABA), free amino acids (FAAs), statins, and isoflavone aglycones was developed using lactic acid bacteria (1:1 mixture of Lactobacillus delbrueckii subsp. latis KFRI 01181 and Lactobacillus plantarum KFRI 00144) and Monascus-fermented soybean extract (MFSE, 1.5%, w/v). Changes in the content of some functional components (GABA, FAAs, statins, isoflavones) and physical (pH, titratable acidity, water-holding capacity), biological (viable cell counts), and sensory characteristics of sogurts during fermentation and cold storage were examined. The medicinal sogurt contained significantly (p < 0.05) high levels of FAAs (2011.2 +/- 8.1 mg/100 g of dry weight of sogurt), GABA (45.5 +/- 1.9 mg), statins (100.1 +/- 7.5 microg), and isoflavone aglycones (56.4 +/- 4.6 mg) compared with the control sogurt (1167.1 +/- 8.1 mg, 32.1 +/- 2.5 mg, not detected, and 19.2 +/- 1.9 mg, respectively) after fermentation for 24 h at 35 degrees C. During cold storage for 30 days at 4 degrees C, medicinal sogurt displayed higher water-holding capacity and titratable acidity and total bacterial cells and lower pH than the control sogurt (p < 0.05). Overall sensory acceptability of medicinal sogurt supplemented with MFSE was higher than that of the control sogurt prepared without MFSE. The results indicate that the addition of the appropriate MFSE concentrations (1.5%, w/v) improved the physicochemical properties as well as sensory characteristics of soy yogurt, resulting in enhanced health-benefit ingredients and consumers' preferences.