Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

Objective To investigate the hypocholesterolemic activity of red yeast rice （RYR） and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR （0.1RYR） or 0.3% RYR （0.3RYR）. Blood （0.5 mL） was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, fiver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 34 folds compared with the conlrol value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Different Solid-state Fermentation technology of Functional Red yeast rice has an effect on the morphological change of MonacolinK

Different technical conditions in the process of solid-state fermentation of red yeast rice has a certain impact on the production of acid-form and lactone form Monacolin K.When cultured in the loose rice medium,the acid form Monacolin K accounts for 50%-60%;while the acid form Monacolin K accounts for 80%-90%cultured in the consolidated rice medium.And we also found that the proportion of the acid form and lactone form Monacolin K will decrease with the increase of fermentation time.

Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical practice.However,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been quantified.Objective:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.Search strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.Data extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third researcher.Based on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were determined.The associations’effect estimates were re-evaluated using random-effect models.Results:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were identified.Based on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible metaanalyses.Based on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate transaminase levels.The other 46(75.4%)associations showed no significant difference between the use of RYR preparations and control treatments.Regarding the credibility of the evidence,21(34.4%),34(55.7%)and 6(9.8%)associations showed moderate,low and very low credibility,respectively.Conclusion:The evidence examined in this study suggests that RYR preparations are safe;however,the credibility of the evidence was not high.Further high-quality evidence is required.

Red Yeast Rice Prevents Atherosclerosis through Regulating Inflammatory Signaling Pathways

Objective： To observe the effects of red yeast rice（RYR） on blood lipid levels, aortic atherosclerosis（AS）, and plaque stability in apolipoprotein E gene knockout（Apo E-/-） mice. Methods： Twentyfour Apo E-/-mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups（n = 8 in each group）： model group（Apo E-/-group）, RYR group（Apo E-/-＋ RYR group）, and simvastatin group（Apo E-/-＋ simvastatin group）. Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were measured with enzymelinked immunosorbent assay. The level of high sensitivity C-reaction protein（Hs-CRP） was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9（MMP-9） and nuclear factor κB（NF-κB） in aorta were tested by immunohistochemistry. Results： Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein（a）, and apolipoprotein B100 in Apo E-/-mice（P〈0.01）. Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α（P〈0.01）. RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. Conclusions： RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflammatory signaling pathways.

No Additional Cholesterol-Lowering Effect Observed in the Combined Treatment of Red Yeast Rice and Lactobacillus Casei in Hyperlipidemic Patients：A Double-Blind Randomized Controlled Clinical Trial

Objective：To observe the effect of combining red yeast rice and Lactobacillus casei（L.casei）in lowering cholesterol in patients with primary hyperlipidemia,the later has also been shown to remove cholesterol in in vitro studies.Methods：A double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L.casei.Sixty patients with primary hyperlipidemia were recruited and randomized equal y to either the treatment group（red yeast rice＋L.casei）or the control group（red yeast rice＋placebo）.One red yeast rice capsule and two L.casei capsules were taken twice a day.The treatment lasted for 8 weeks,with an extended follow-up period of 4 weeks.The primary endpoint was a difference of serum low-density lipoprotein cholesterol（LDL-C）level at week 8.Results：At week 8,the LDL-C serum level in both groups was lower than that at baseline,with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group;however,there was no statistical difference between the two groups（P〉0.05）.The total cholesterol was also lower than the baseline in both groups,yet without a statistical difference between the two groups.The only statistical y significant difference between the two groups was the average diastolic pressure at week 12,which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group（P〈0.05）.The antihypertensive activity may be associated with L.casei.Red yeast rice can significantly reduce LDL-C,total cholesterol and triglyceride.Conclusion：The combination of red yeast rice and L.casei did not have an additional effect on lipid profiles.

Statin alternatives or just placebo： an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics

Objective The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy. Data source A PubMed search was conducted using the keywords ＇trial, omega-3, red yeast rice, xuezhikang, garlic, cholesterol, cardiovascular, outcomes＇; the resulting trials were reviewed together with the references quoted in the papers obtained. Study selection The studies selected are prospective, randomized, placebo-controlled studies with predefined clinical cardiovascular end-points recruiting at least 2000 patients, with a follow-up over 2 years. Results Modest dose omega-3 fatty acid has been shown in GISSI-P （11 324 patients, follow-up 3.5 years） to produce a reduction in sudden death of 45%, and in cardiac death of 35%, acting probably via an anti-arrhythmic effect. In JELLS （18 645 patients, follow-up 4.6 years）, high dose omega-3 given to Japanese patients on a high fish diet and already on statin treatment produced further benefit with a 19% reduction of nonfatal cardiovascular outcomes; fatal cardiac events are not affected. CCSPS （4870 patients, follow-up 4 years）, a secondary prevention trial using xuezhikang, a commercial red yeast rice preparation, produced a 46% reduction in nonfatal myocardial infarction and coronary death. There has been no trial to show that garlic reduces clinical cardiovascular outcomes. A rigorous trial with constant assessment of chemicals in the study material in 192 patients found that over a 6-month follow-up, raw garlic and 2 commercial preparations do not significantly affect lipid levels. Conclusions Omega-3 in modest doses reduces cardiac deaths, and in high doses reduces nonfatal cardiovascular events. Red yeast rice reduces adverse cardiac events to a similar degree as the statins. It is unlikely that garlic is useful in preventing cardiovascular disease.

Effectiveness and safety of red yeast rice predominated by monacolin Kβ-hydroxy acid form for hyperlipidemia treatment and management

OBJECTIVE:To assess the lipid-lowering activity and safety of a dietary supplement containing monacolin Kβ-hydroxy acid form(MKA),Heye(Folium Nelumbinis),and Cangzhu(Rhizoma Atractylodis Lanceae),compared to lifestyle modifications.METHODS:Totally 117 subjects with moderate to severe dyslipidemia(according to Chinese guidelines)and low CV risk were randomly assigned into three treatment groups:lifestyle modification(LM),LM plus a low dosage of MKA,LM plus a high dosage of MKA,and treated for 60 d.The primary endpoint was the reduction of low density lipoprotein cholesterol(LDL-C)and total cholesterol(TC).Safeties along with Traditional Chinese Medicine Syndromes were assessed through the study.RESULTS:A low dosage of MKA along with lifestyle modifications caused a significant decrease in LDL-C by 15.6%on average(95%CI,9.6%to 21%)with,a decrease in TC by 15.3%on average(95%CI,9.26%to 21.4%),and a decrease in non-HDL-C by 35.4%(95%CI,25.76%to 41.34%).Weak evidence of a reduction of triglycerides but an increment of HDL-C was observed in patients with severe hyperlipidemia.No severe adverse events occurred during the study.CONCLUSION:Our results confirm the LDL-C and TC lowering properties of MKA is clinically meaningful.It also produces a significant reduction of non-HDL-C,and slightly effects on TG and HDL-C as well.

The current trend and challenges of developing red yeast rice-based food supplements for hypercholesterolemia

Hypercholesterolemia is a risk factor of cardiovascular diseases,which have been managed using statin drugs.Red yeast rice(RYR)as a traditional food in the Eastern Asia countries has anti-hyperlipidemia activity.Recently,a variety of food supplement products containing RYR have been developed to lower blood cholesterol,which is attributed to the presence of monacolins,especially monacolin K(lovastatin,a statin drug).This review was aimed to summarize the clinical trials using RYR products to investigate their effects on lipid profiles in humans.Relevant articles of human clinical trials were retrieved from PubMed and discussed here.Results showed that RYR and its extracts have been included in commercially available products alone and in combinations with various other materials,which include bioactive compounds such as coenzyme Q10 and berberine,vitamins,extracts from other plants such as phytosterols,polyunsaturated fatty acids or even probiotics.The durations of the trials ranged from 4 weeks to 60 months.The content of monacolin K ranged from 0.32 mg/pack to 10 mg/pack.The data of these human clinical trials demonstrated that these RYR supplement products were sufficient to reduce blood cholesterol in different populations.However,the inclusions of certain materials might not have additive effect.Additionally,studies including a lovastatin only positive control group with the equivalent dose as that of monacolin K in the RYR products remain to be done.Furthermore,variations of monacolin K contents and presence of toxic citrinin are still concerns.Last,bioactivities of other components in RYR should be investigated as well.More future studies will certainly help to fully explore the potentials of this traditional food in the combat against cardiovascular and other metabolic diseases.

Potential protective effects of red yeast rice in endothelial function against atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease(ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice(RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.

Six new monacolin analogs from red yeast rice

Six novel monacolin analogs, monacolins V_1–V_6(1–6), together with seven known ones(7–13), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods,especially 2D NMR(~1H-~1HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation.Monacolins V_2(2) and V_3(3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide(LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.

红曲复合营养米制备工艺及其食味品质研究

利用双螺杆挤压技术制备红曲复合营养米。以莫纳克林K含量和感官得分为指标,通过单因素与正交试验优化制备工艺参数,利用电子舌和电子鼻对产品食味品质进行评价。结果表明:当挤压四区温度为90℃、螺杆转速为120 r/min、喂料速度为8 kg/h时,得到的红曲复合营养米的感官得分及莫纳克林K含量最高。随着功能性红曲米粉添加量的增加,红曲复合营养米的食味品质有明显区别。以籼米粉质量为基准,当功能性红曲米粉添加量为2.0%时,红曲复合营养米在鲜味和咸味上指数适中,且苦味、涩味指数较低,能够赋予产品更佳的食味品质。

红曲类制剂临床研究进展

红曲米是中国传统中药,近代研究发现红曲米内含有莫奈克林-K(Monaclin K),其具有降低血脂作用,由此研发的他汀类药物在降低血脂、延缓及逆转动脉粥样硬化斑块,防治心血管病起到明显作用,并被国内外各类指南推荐。正是由于他汀类药物在临床的有效使用,引起对含有莫奈克林-K的红曲类制剂的关注和研究。本文收集红曲类制剂,包括药品和保健食品相关的临床研究文献,并对其临床试验研究的有效性、安全性及使用注意事项进行综述,为红曲米制剂的使用提供参考。

红曲中辅酶Q10 的研究进展

本文对红曲中辅酶Q10的来源、产量提升方法、检测方法、提取技术及其应用前景进行了综述,为含辅酶Q10的红曲生产与应用提供参考。辅酶Q10是红曲霉的重要代谢产物之一,不仅展现出多种生物活性,还能有效减轻红曲中他汀类成分的副作用。提高红曲中辅酶Q10含量的方法主要有优化发酵条件、选育高产菌株。辅酶Q10的测定方法主要有光谱法和色谱法。在提取技术上,主要采用皂化法、超声波提取法和超临界萃取法等来提取微生物来源的辅酶Q10。目前微生物来源的辅酶Q10被应用于医药、食品和化妆品等领域。

红曲菌几种主要次级代谢产物及其生物活性的研究进展

红曲在我国古代也称"丹曲",传统的红曲是指以大米为原料,接种红曲菌经固态发酵而成的红曲米。红曲在中医上具有健脾化食、燥湿化痰、活血化瘀等功效;工业上常用于制作红曲米酒和腌渍肉、鱼等。红曲菌能产生多种次级代谢产物,例如红曲色素、莫纳可林K(MonacolinK,MK)、γ-氨基丁酸(GABA)、抗氧化物质、降血压物质等,其中部分代谢产物具有降血压、降血脂、抗菌、抗氧化和抗癌等重要的生理活性。本文介绍了近年来红曲菌几种主要次级代谢产物及其生物活性的研究进展。

红曲降血脂功能的研究及应用概况

红曲是以大米为原料,经红曲霉发酵而成的一种紫红色米曲,具有显著的降血脂功能。本文阐述了红曲与其他活性物质合理复配或根据中医原理与中药材复配具有很好的药理作用的研究;阐释了红曲降血脂功效大于纯洛伐他汀的原理,可能与红曲中各化合物协同作用、莫纳可林K的空间结构、口服生物药效率等有关;并阐述了红曲对有他汀不耐症的高血脂患者降血脂作用的研究,表明了红曲具有很好的耐受性;介绍了国内外红曲降血脂功能在保健食品上的应用,并对红曲中桔青霉素和红曲与其他药物相互作用这两个安全性问题的研究进展进行了总结,最后对今后红曲的发展方向进行了展望。

红曲的生产工艺及Monacolin K和桔霉素的检测

综述红曲的生产工艺及MonacolinK和桔霉素的检测方法,指出采用新型生产工艺、优化发酵条件和应用菌种筛选等现代技术是生产既富含活性成分MonacolinK又不含桔霉素的功能性红曲的重要途径,同时预示MonacolinK和桔霉素检测技术的进展将为功能性红曲产品的质量、安全使用及国际市场的开拓提供技术支撑。

中药红曲化学稳定性多成分综合评价

建立了利用高效液相色谱法同时测定红曲中具降血脂活性的12种他汀类成分的方法,并进行方法学评价.研究了红曲在高温(80及60℃)、高温高湿(60℃及75%RH)、室温高湿(25℃及92.5%RH)和光照等条件下的化学稳定性,在40℃及75%RH的条件下进行3个月的加速试验.通过测定稳定性试验样品中12种他汀类成分的含量,考察了红曲中这些成分的动态变化情况,并加以综合评价.

红曲抗炎作用的实验研究

目的:研究红曲的抗炎作用。方法:急性抗炎模型采用巴豆油致小鼠耳肿胀模型和角叉莱胶致大鼠足肿胀模型,慢性抗炎模型采用棉球植入小鼠腹腔致肉芽肿模型。以布洛芬作阳性对照,并设洛伐他汀高、低剂量组。比较红曲与洛伐他汀的抗炎作用。结果:红曲对巴豆油致小鼠耳肿胀、角叉菜胶致大鼠足肿胀和棉球致小鼠腹腔肉芽肿均有显著的抑制作用,与洛伐他汀的抗炎作用相近。结论:红曲具有显著的抗炎作用。

中药红曲复方制剂降脂作用的实验研究

[目的]探讨中药红曲复方制剂对降低高脂血症模型大鼠血脂水平的疗效。[方法]采用高脂饲料喂养SD大鼠建立预防性高脂血症模型,将实验大鼠分成阴性对照组、模型对照组、阳性对照组、低剂量组、中剂量组和高剂量组。连续灌胃给药30d,观察中药红曲复方制剂对高脂血症大鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的影响。[结果]与阴性对照组比较,高脂饲料连续喂养30d后,模型对照组大鼠血清TG、TC和LDL-C显著升高(P<0.01);与模型对照组比较,给药30d后,阳性对照组TG、TC和LDL-C显著降低(P<0.05);低剂量组大鼠血清TG显著降低(P<0.05),中剂量组和高剂量组血清TG、TC和LDL-C显著地降低(P<0.01);各剂量组大鼠血清HDL-C无统计学差异(P>0.05)。[结论 ]中药红曲复方制剂可有效控制并降低血脂水平。

利用紫外线和氯化锂诱变筛选高产Monacolin K的红曲突变株(英文)

In the 1970's, a Japanese scientist discoveredthat some strains of Monascus spp. when theygrew on rice might produce a certain secondary me-tabolite, known collectively as Monacolin K,which could effectively inhibit HMG-CoA reduc-tase and had many bio-activities such as