| Summary: | 碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 94 === Monascus, one of the Chinese traditional fermentation fungi, has been used for thousands of years. It has been recorded in ancient Chinese books for its special functions and food applications. For instance, in China, monascus have been widely used as a natural food coloring agent for many kinds of foods. The metabolite of Monascus species, specifically, monacolin K, γ-amino butyric acid (GABA) and dimerumic acid, have been proven to have cholesterol-lowering effects, blood-pressure-lowering effects, and antioxidant effects. Nowadays, the public has recognized the importance of monascus products for its many health benefits; therefore, it is not surprising that monascus has become the focus of many studies as functional foods.
The aim of this study is to determine the feasibility of using wet milling technology to formulate crude red mold rice (RMR) as stable nanoparticulate dispersion and evaluate its safety and cholesterol lowering effect. Red mold rice nanoparticulate formulation (NRMR) was reproducibly obtained after milling RMR in the presence of distilled water. The physical and chemical properties of these particles were studied using electron microscopy, laser light scattering and high performance liquid chromatography (HPLC). To verify safety and/or functionality evaluations, Ames test, cytotoxicity, in vivo 28-day feeding toxicity in Wistar rats and in vivo cholesterol-lowering effect in hypercholesterolemic hamsters were processed using RMR and NRMR. RMR (mean size = 20.2 μm) was processed using wet milling technology to form an aqueous-based nanoparticle dispersion with a mean particle size of 259 nm. The formulation was homogeneous and exhibited a unimodal particle size distribution profile using dynamic laser scattering techniques. In addition, HPLC analyses, performed on the second metabolite, demonstrated that monacolin K was reduced to 75.2% of its base level, and citrinin was reduced to 74.6% of its base level. Partial agglomeration has been observed in RMR dispersion when stored in refrigerator after 2 months. Cytotoxicity test demonstrates that 4.22 mg/mL of RMR nanoparticulate, extracted with alcohol, has resulted in 50% lethality in Hep G2 cells. Ames test shows the absence of genotoxicity in Salmonella typhimurium TA 98, TA 100 and TA 102 when treated with less than 1 mg of extract per plate. In feeding toxicity, the no observed adverse effect level (NOAEL) of NRMR, administered to Wistar rats via oral gavages for 28 days, was 500 mg/kg/day for male rats and 1000 mg/kg/day for female rats. In vivo cholesterol-lowering effect in hypercholesterolemic hamsters, plasma LDL/HDL ratio (LDL: low density lipoprotein; HDL high density lipoprotein), liver TC (total cholesterol) and TG (triglyceride) levels in hamster fed with NRMR dispersion at dosage (20 mg/110 g bw/day) for 8 weeks were significantly lower than that in hyperlipidemia hamster.
In conclusion, red mold rice can be formulated as a stable and bioactive nanoparticulate dispersion using wet milling technology. And in vitro and in vivo safety evaluations indicate that no mutagenic or toxic responses were observed in this study.
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