Monacolin K, an inhibitor for cholesterol synthesis, is the secondary metabolite of Monascus species. The formation of the secondary metabolites of the Monascus species is affected by cultivation environment and method. This research uses sweet potato (Ipomoea batatas), potato (Solanum tuberosum), casava (Manihot esculenta), and dioscorea (Dioscorea batatas) as the substrates and discusses the best substrate to produce monacolin K. The results show that Monascus purpureus NTU 301, with dioscorea as the substrate, can produce monacolin K at 2,584 mg kg(-1), which is 5.37 times to that resulted when rice is used as the substrate. In addition, more amount of yellow pigment can be found in Monascus-fermented dioscorea than in Monascus-fermented rice. The certain composition of yellow pigment is identified as monascin, which has been shown as an antiinflammation agent exhibiting potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice in previous studies. Therefore, dioscorea is concluded to be the best substrate for Monascus species to produce the cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin.
Monascus or more commonly known as red mold rice is fermented rice on which Monascus purpureus has been grown. It has been a traditional Chinese food additive for thousands of years in China. Secondary metabolite product of Monascus, monacolin K, has been proven that it could be used as an antihypercholesterolemic agent. In this study, M. purpureus NTU568 mutated and selected from a monacolin K productivity strain-M. purpureus HM105 produced high quantities of monacolin K at a level of 9,500 mg kg(-1). This research focused on the effect of adding red mold rice powder of M. purpureus NTU568 to a hamster diet on total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C). In the results, the oral administration of Monascus powder in hyperlipidemia hamster was indeed proven to decrease TC, TG, and LDL-C levels. Plasma TC levels in hamster fed with Monascus powder at one-fold dosage [10.78 mg (day 100 g bw)(-1)] for 4 and 8 weeks were significantly lower (31.2 and 22.0%, respectively) than that in hyperlipidemia hamster. Plasma TG (30.1 and 17.9%) and LDL-C levels (36.0 and 20.7%) were also significantly lowered by feeding Monascus powder at one-fold dosage for 4 and 8 weeks compared to hyperlipidemia hamster. In addition, examinations of liver TC and TG levels of hyperlipidemia hamster were also performed and showed similar effects on lipid-lowering action by oral administration of Monascus powder. Since citrinin is a mycotoxin that possesses nephrotoxic and hepatoxic effects, it has a negative impact on the safety of red mold rice for people. This study examined the liver somatic index [plasma glutamyl oxaloacetic transaminase (GOT) and glutamyl pyruvic transaminase (GPT) levels] and liver biopsy to investigate whether Monascus powder induced damage in liver. It was found that the plasma GOT and GPT levels were not significantly increased by feeding Monascus powder. There was no difference in the results of the liver biopsy between the Monascus powder-treated groups and the control group.
This study evaluated the effect of red mold rice supplementation on antifatigue and exercise-related changes in lipid peroxidation of male adult Wistar rats through swimming exercise. Thirty 16-week-old rats were studied by dividing them into three groups (ten for each group). Other than the control group (CD), the other two groups were divided into a high-dose (HD) treatment group (5 g red mold rice/kg body weight for the HD group), and a low-dose (LD) group (1 g red mold rice/kg body weight for the LD group). Swimming endurance tests were conducted after 28 days of red mold rice supplementation, and the result showed that the treatment group showed a higher exercise time (CD, 78.0+/-6.4; LD, 104.2+/-9.6; and HD, 129.4+/-10.9 min; p<0.05) and a higher blood glucose concentration (CD, 76.67+/-8.08; LD, 111.34+/-8.50; and HD, 117.67+/-11.06 mg/dl; p<0.05) than the CD. Moreover, the blood lactate (CD, 45.00+/-0.90; LD, 31.41+/-1.80; and HD, 28.89+/-1.62 mg/dl; p<0.05), blood urea nitrogen (CD, 21.87+/-0.75; LD, 20.33+/-0.83; and HD, 20.53+/-1.09 mg/dl; p<0.05), and hemoglobin (CD, 14.20+/-0.21; LD, 13.70+/-0.55; and HD, 13.28+/-0.35 g/dl; p<0.05) were also significantly lower than those of the CD. Besides, the result suggested that the red mold rice supplementation may decrease the contribution of exercise-induced oxidative stress and improve the physiological condition of the rats.
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.
Monascus-fermented red mold dioscorea (RMD) was proven to produce higher monacolin K levels than red mold rice (RMR) in our previous study. The goal of this study is to investigate whether the novel RMD had more hypolipidemic and antiatherosclerotic effect than traditional red mold rice. The daily dose of RMR for adults was recommended as 1 g, which corresponded to 96 mg/kg/day for hamsters. Therefore, high cholesterol diet-induced hyperlipidemic hamsters were daily administrated with a 0.5-fold (48 mg/kg/day), a 1-fold (96 mg/kg/day), or a 5-fold dose (480 mg/kg/day) of RMD for 8 weeks. Furthermore, a 1-fold dose of RMR (96 mg/kg/day) and unfermented dioscorea (96 mg/kg/day) were also respectively used to evaluate the effect of hypolipidemic and antiarteriosclerosis. The results indicated that only needing a 0.5-fold dose of RMD was able to significantly lower total cholesterol (by 13.78%, p<0.001), triglyceride (by 38.74%, p<0.01), and low-density lipoprotein cholesterol levels (by 43.11%, p<0.05) as well as maintain a high-density lipoprotein cholesterol level, as compared to the hyperlipidemic group. RMD including a higher monacolin K level and a dioscorea substrate was able to exhibit a more significant difference in the hypolipidemic effect than RMR or unfermented dioscorea. Both RMR and dioscorea exhibited potent in vitro antioxidative ability and in vivo protection against hypolipidemia-induced oxidative stress. Therefore, the antioxidative ability of RMD provided by Monascus metabolites (dimerumic acid, tannin, phenol, etc.) as well as dioscorea was able to perform more antiatherosclerotic effects on increasing total antioxidant status, catalase, and superoxide dismutase activity and repressing lipid peroxidation and atherosclerotic plaque than RMR and dioscorea.
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.
Amyloid beta (Abeta) peptide related to the onset of Alzheimer's disease (AD) damaged neurons and further resulted in dementia. Monascus-fermented red mold rice (RMR), a traditional Chinese medicine as well as health food, includes monacolins (with the same function as statins) and multifunctional metabolites. In this study, ethanol extract of RMR (RE) was used to evaluate neuroprotection against Abeta40 neurotoxicity in PC12 cells. Furthermore, the effects of dietary administration of RMR on memory and learning abilities are confirmed in an animal model of AD rats infused with Abeta40 into the cerebral ventricle. During continuous Abeta40 infusion for 28 days, the rats of test groups were administered RMR or lovastatin. Memory and learning abilities were evaluated in the water maze and passive avoidance tasks. After sacrifice, cerebral cortex and hippocampus were collected for the examination of AD risk factors. The in vitro results clearly indicate that RE provides stronger neuroprotection in rescuing cell viability as well as repressing inflammatory response and oxidative stress. RMR administration potently reverses the memory deficit in the memory task. Abeta40 infusion increases acetylcholinesterase activity, reactive oxygen species, and lipid peroxidation and decreases total antioxidant status and superoxide dismutase activity in brain, but these damages were potently reversed by RMR administration, and the protection was more significant than that with lovastatin administration. The protection provided by RMR is able to prevent Abeta fibrils from being formed and deposited in hippocampus and further decrease Abeta40 accumulation, even though Abeta40 solution was infused into brain continuously.
In this study, the milk-soymilk and milk-soymilk supplemented with Momordica charantia , a common oriental vegetable possessing medicinal activities, were fermented by lactic bacteria. The objective of this study was to investigate the effects of milk-soymilk and fermented milk-soymilk with or without M. charantia on atherosclerosis in hyperlipidemic hamsters. Fermented 25% milk and 75% soymilk combinations, supplemented with 1% M. charantia solution, can improve the acceptability of the fermented beverage. A total of 72 male Golden Syrian hamsters were divided into 9 groups (n = 8/group), and experimental diets were provided with a normal diet for the normal group and a high-cholesterol diet for others. The milk-soymilk and fermented milk-soymilk with or without M. charantia were administrated for 8 weeks. The milk-soymilk and fermented milk-soymilk with and without M. charantia were able to significantly decrease (p < 0.05) the serum cholesterol and the atherosclerotic plaque in aorta based on the comparison to the high-cholesterol diet (H) group. The groups on fermented milk-soymilk by Lactobacillus plantarum NTU 102 with or without M. charantia could significantly decrease (p < 0.05) the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C). The femented milk-soymilk by Lactobacillus paracasei subsp. paracasei NTU 101 supplemented with M. charantia had an anti-atherosclerotic activity by increasing superoxide dismutase (SOD) and total antioxidant status (TAS) activity of the blood and relieving the degree of thiobarbituric acid reactive substances (TBARS) compared to the other treatments. It is concluded that the milk-soymilk and the fermented milk-soymilk supplemented with or without M. charantia by L. paracasei subsp. paracasei NTU 101 are effective in preventing and retarding the hyperlipidemia-induced oxidative stress and atherosclerosis.
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