The pharmacology and mechanism of action of Monascus purpureus Went: a scoping review

Abstract

Objective:

The aim of this study is to review the recent studies on the pharmacology and mechanism of action of Monascus purpureus Went, analyze its medicinal value, and explore future research directions.

Method:

A scoping review was conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, SinoMed, and PubMed from inception until September 2024. The basic information of the included studies, such as study types, disease types, main components, outcomes, and efficacy, was reviewed and summarized. Methodological quality was assessed using the SYRCLE’s risk of bias assessment tool for animal studies and the Cochrane risk of bias assessment tool for clinical trials.

Results:

We identified 251 studies from the five databases. Among them, 153 were experimental studies, 70 were reviews, and 28 were clinical trials. Of the experimental studies, molecular studies accounted for the largest portion, totaling 80 (52%). Among the reviews, research progress accounted for the most, totaling 41 (59%). The clinical trials studied the effects of Monascus purpureus Went and its related Chinese patent medicines and preparations. Of these, 17 (61%) used Monascus purpureus Went-related Chinese patent medicines and preparations as interventions and 11 (39%) used traditional Chinese medicine (TCM) formulations of Monascus purpureus Went as interventions. In terms of methodological quality, both animal studies and clinical trials related to Monascus purpureus Went showed deficiencies in randomized allocation sequence generation, allocation concealment, and blinding methods.

Conclusion:

We summarized existing studies on the active ingredients and effects of Monascus purpureus Went and found that it is necessary to improve the generation of random allocation sequences and the application of the blinding method in Monascus purpureus Went-related animal studies and clinical trials. When similar studies are conducted in the future, the specific methods of random assignment should be more clearly described, and blinding methods should be applied to improve the objectivity and accuracy of the studies, thereby providing a reference for selecting future research directions and establishing supporting evidence.

1 Introduction

Monascus purpureus Went is a traditional Chinese medicine (TCM) with a long history, produced through the fermentation of ordinary rice using Monascus species (Chen et al., 2000). It is mainly produced in Fujian, Zhejiang, and Jiangxi. Additionally, Monascus purpureus Went is sweet in taste, warm in nature, and belongs to the liver, spleen, stomach, and large intestine meridians, according to TCM theory. It is recorded in the Supplement to Augmented Materia Medica that Monascus purpureus Went has the effects of “promoting blood circulation and helping digestion, strengthening the spleen and warming the stomach, treating dysentery, and bringing down water.” Clinically, Monascus purpureus Went is mainly used to treat postpartum lochia, abdominal pain with stagnation, food accumulation and fullness, dysentery, and bruises (Song et al., 1999a).

In 2024, Japan’s Kobayashi Pharmaceutical Co., Ltd. experienced a safety incident involving “health products containing Monascus purpureus Went ingredients.” After investigation, the issue was potentially caused by contamination of the Monascus purpureus Went fermentation raw materials with penicillic acid or by inadequate cleanliness in the production environment, lead to the presence of penicillium mixed. This incident once again brought the efficacy and safety of red yeast into the global social hot spot (Ma 2025; Sun, 2025; Zhu et al., 2025).

Modern pharmacology has discovered that Monascus purpureus Went has lipid-lowering, anti-tumor, antioxidant, anti-osteoporosis, antibacterial, and other effects (Wei et al., 2023). In addition, Monascus purpureus Went has a wide range of applications in brewing, fermented foods, food coloring, and other fields. In recent years, new application fields have been gradually developed, such as animal husbandry and veterinary medicine, feed fermentation, healthy fermented foods, healthy drinks, and healthy seasonings (Xie, 1996). In recent years, the extraction of the lipid-lowering component lovastatin from Monascus purpureus Went (Endo, 1980) has further enhanced the research value of Monascus purpureus Went, attracting great attention from scholars both at home and abroad. The significant lipid-lowering effect and medicinal potential of lovastatin have inspired many scholars to conduct studies on the pharmacology and mechanism of action of this new component in Monascus purpureus Went, resulting in many remarkable findings, such as studying the lipid-lowering mechanism and content determination method of lovastatin (Wen et al., 2001), optimizing the extraction process of lovastatin from Monascus purpureus Went (Wang et al., 2024a), and producing drugs mainly composed of lovastatin, such as Xuezhikang (Kong et al., 2005). At present, the pharmacological research on Monascus purpureus Went still needs to be improved to further understand and develop its medicinal value and expand its application range.

A large number of studies on Monascus purpureus Went have been published, including reviews (Wang et al., 2024b). However, these published reviews lacked a comprehensive literature search, which led to limited references and unreliable evidence evaluation. Such limitations may introduce certain biases into the review, which is not conducive to the reference of other studies. In contrast, this study conducts a scoping review based on evidence-based medicine methods to systematically summarize the recent studies on the pharmacology and mechanism of action of Monascus purpureus Went, analyze its medicinal value, and explore future research directions.

2 Data and methods

2.1 Search strategy

Five databases, namely, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, SinoMed, and PubMed, were searched from inception to September 2024. The search terms consisted of Monascus purpureus Went, Monascus, Monascus purpureus Went, pharmacology, pharmacological effect, pharmacological mechanism, biological activity, and active ingredient. The full search terms of all databases are shown in Supplementary Add S1.

2.2 Inclusion and exclusion criteria

Inclusion criteria: Studies focused on Monascus purpureus Went; study types were not limited, and the language was English or Chinese.

Exclusion criteria: Manuscripts with unavailable full text and duplicate publications were excluded. News reports, conference papers, or dissertations were also excluded.

2.3 Study screening and data extraction

The screening and extraction process was as follows: 1) NoteExpress software was used to exclude duplicate studies, 2) two reviewers performed an initial screening after reading the titles and abstracts based on the inclusion and exclusion criteria, 3) the full text was reviewed when additional information was needed for screening, and 4) any disagreements were resolved through discussion with a third researcher.

The basic information in the included studies, such as title, authors, year of publication, type of study, subject of study, study population, study method, intervention, duration of treatment, dosage, control measure, measurement index, method of measurement, result, and conclusion, was extracted.

2.4 Data analysis

We analyzed all extracted data fields, including bibliometric statistics, visual data analysis, and evidence graph analysis. We also systematically organized and comprehensively summarized study evidence information.

2.5 Quality assessment

Two reviewers assessed the methodological quality of the included studies, including animal studies and clinical trials, as this is an integral part of evidence-based research. The SYRCLE’s risk of bias assessment tool was used to assess the quality of animal studies, and the Cochrane risk of bias assessment tool was used to assess the quality of randomized controlled trials (RCTs). The evaluation results were indicated as “low risk,” “high risk,” or “unclear risk.”

3 Results

3.1 Search results

A total of 2,494 studies were initially searched. Among them, 970 were duplicates, and 1,223 were excluded after reading the title or abstract. Among 301 studies assessed in full text, 50 were excluded for the following reasons: not focusing on Monascus purpureus Went (n = 41) and lack of full text (n = 9). Finally, 251 studies were included in the final review.

The study screening process is presented in Figure 1.

FIGURE 1

3.2 Characteristics of included studies

A total of 251 literature studies were included, comprising 242 Chinese publications (96%) and 9 English publications (4%). There were 153 experimental studies (61%), 70 reviews (28%), and 28 clinical trials (11%). The included studies were published between 1988 and 2024, with the highest number published in 2007 (n = 18). The number of studies published each year is presented in Figure 2.

FIGURE 2

We summarized and generalized evidence from studies on Monascus purpureus Went, including its definition, origin, fermentation strain, morphological features, production process, acquisition methods, ingredients, identification methods, clinical efficacy, safety evaluation, and applications. The chart of evidence from studies on Monascus purpureus Went is presented in Figure 3.

FIGURE 3

Among the experimental studies, molecular studies accounted for most of them, totaling 80 (52%). Among the reviews, research progress accounted for most of the studies, totaling 41 (59%). Clinical trials studied the effects of Monascus purpureus Went and its related Chinese patent medicine in the treatment of diseases, with 17 (61%) using Monascus purpureus Went-related Chinese patent medicines and preparations as interventions and 11 (39%) using TCM formulations of Monascus purpureus Went as interventions. The details of the research topics of the included studies are shown in Table 1.

3.3 Experimental study

3.3.1 Molecular study

Eighty molecular studies related to Monascus purpureus Went were included.

3.3.1.1 Content determination

Forty studies determined the content of active ingredients in Monascus purpureus Went, with lovastatin and citrinin (orange mold) being the most common ingredients. The methods for content determination included high-performance liquid chromatography (HPLC) (n = 29), thin-layer chromatography scan (TLCS) (n = 2), capillary electrophoresis (CE) (n = 2), automatic amino acid analyzer (AA) (n = 2), gas chromatography (GC) (n = 1), quick, easy, cheap, effective, rugged, safe–ultra-performance liquid chromatography–multiple reaction monitoring–ion-dependent acquisition–criteria-enhanced product ion (QuEChERS-UPLC-MRM-IDA-Criteria-EPI) (n = 1), phenol–sulfuric acid (PSA) (n = 1), anthrone–sulfuric acid (ASA) (n = 1), dinitrosalicylic acid (DNS) (n = 1), flame atomic absorption spectroscopy (FAAS) (n = 1), and statistical analyses including statistical package for the social sciences principal component analysis and cluster analysis (SPSS PCA and SPSS CA) (n = 1).

3.3.1.2 Chemical property

Fourteen studies examined the chemical properties of the active ingredients in Monascus purpureus Went, including antioxidant activity (n = 5), chemical structure (n = 5), lipid-lowering activity (n = 2), poisoning mechanism (n = 1), and protease and amylase activities (n = 1).

3.3.1.3 Monascus purpureus Went identification method

Thirteen studies examined the methods for identifying different Monascus purpureus Went strains using chromatography (n = 6), spectroscopy (n = 4), random amplified polymorphic DNA (RAPD) (n = 2), and secondary metabolite fingerprint (SMF) (n = 1).

3.3.1.4 Component extraction process

3.3.1.5 Strain identification and screening

Five studies examined the identification and screening of Monascus purpureus Went strains based on molecular biology.

3.3.2 Animal study

Among the 58 animal studies, 54 used rat models (93%), 3 used rabbit models, and 1 used the quail model. A total of 55 studies determined the efficacy of Monascus purpureus Went, including double-armed studies (n = 6), three-armed studies (n = 10), and multi-armed studies (n = 39). Three studies determined the safety of erythromycin, including a two-armed study (n = 1), a three-armed study (n = 1), and a multi-armed study (n = 1). Fifty-four studies contained a blank control, and four studies did not contain a blank control.

Among them, 26 studies showed that Monascus purpureus Went had lipid lowering effects, involving TCM Monascus purpureus Went (n = 5), Monascus purpureus Went compound preparation (n = 3), vinegar bean lipid-lowering capsule (n = 1), Monascus purpureus Went earthworm (Pheretima) protein tablet (n = 1), Monascus purpureus Went Allium sativum L. fermentation extract (n = 1), Monascus purpureus Went Poria cocos (Schw.) Wolf tablet (n = 1), compounded Monascus purpureus Went capsule (n = 1), a mixture of Monascus purpureus Went and grape seed anthocyanidin (n = 1), Monascus purpureus Went bee glue tablet (n = 1), Xuezhikang capsule (n = 1), lovastatin (n = 1), natto (Glycine max) Monascus purpureus Went (n = 1), Ginkgo biloba L. Monascus purpureus Went vitamin grouping (n = 1), Monascus purpureus Went combined with Fang Feng Tong Sheng powder (n = 1), Fagopyrum esculentum Moench Monascus purpureus Went powder (n = 1), Monascus purpureus Went–phytosterol ester compound preparation (n = 1), Yunnan Monascus purpureus Went powder (n = 1), compounded Monascus purpureus Went extract (n = 1), yellow Monascus pigment (n = 1), and sea-buckthorn (Hippophae rhamnoides L.) Monascus purpureus Went capsule (n = 1). Twelve studies showed that Monascus purpureus Went had an effect on repairing bones, involving TCM Monascus purpureus Went (n = 11) and Monascus purpureus Went capsule-containing coenzyme Q10 (n = 1); five studies showed that Monascus purpureus Went had an effect on improving fatty liver, involving TCM Monascus purpureus Went (n = 3), Monascus purpureus Went Crataegus pinnatifida Bunge (n = 1), and Coptis chinensis Franch. Monascus purpureus Went medicine (n = 1); four studies showed that Monascus purpureus Went had an effect on lowering blood pressure, involving TCM Monascus purpureus Went (n = 4); three studies showed that Monascus purpureus Went had an effect on anti-inflammation, involving TCM Monascus purpureus Went (n = 3); three studies showed a good safety profile of Monascus purpureus Went, involving Monascus purpureus Went polysaccharide (n = 1), Monascus purpureus Went extract (n = 1), and Panax Notoginseng (Burk.) F.H.Chen Monascus purpureus Went compound preparation (n = 1); two studies showed that Monascus purpureus Went had an effect on tumor inhibition, involving Monascus purpureus Went polysaccharide (n = 2); one study showed that Monascus purpureus Went had an effect on cerebrovascular disease, involving TCM Monascus purpureus Went (n = 1); one study showed that Monascus purpureus Went had an effect on regulating the gastrointestinal tract, involving TCM Monascus purpureus Went (n = 1); and one study showed that Monascus purpureus Went had an effect on treating renal disease, involving Monascus purpureus Went extract (n = 1).

Among these studies, the most commonly used dose was 0.625 g/mL of aqueous Monascus purpureus Went solution, administered via irrigation at 10 mL/kg, and the most commonly used course of treatment was 28 days. The specific information on animal studies is presented in Table 2.

All 58 animal studies were randomized controlled studies. Among them, 55 studies only reported “randomization,” and 3 used the random number table method. A total of 58 studies reported that the experimental group was consistent with the control group at baseline. Fifty-seven studies did not report allocation concealment and blinding, and only one blinded the investigator and the animal keeper. Forty-two studies did not report whether the environments in which the animals were placed were randomized or not, and 16 studies reported that the animals were grown in the same environments; no missing data appeared. The risk of bias assessment of animal studies is presented in Table 3.

3.3.3 Cell study

Fifteen cellular studies related to Monascus purpureus Went were included. Seven studies focused on the identification and screening of Monascus purpureus Went bacterial strains using cell biology techniques. Six studies determined the efficacy of Monascus purpureus Went, including the synthesis and in vitro anticancer activity of Monascus purpureus Went derivatives (n = 1), the blood pressure-lowering mechanism of Monascus purpureus Went (n = 1), the effect of Monascus purpureus Went on the secretion of TNF-alpha by peripheral blood single-nucleated cells of ankylosing spondylitis patients (n = 1), the effect of erythrocytes on the cell growth and molecular mechanisms of HCT-116 cells (n = 1), the effect of Monascus purpureus Went on the proliferation of myocardial fibroblasts (n = 1), and the role of Monascus purpureus Went in inducing apoptosis and autophagy in human colon cancer cells (n = 1).

Two studies examined the physiological characteristics of Monascus purpureus Went and Monascus purpureus Went (n = 1) and the morphological characteristics of TCM Monascus purpureus Went (n = 1).

3.4 Clinical trial

A total of 28 clinical trials studied the effects of TCM Monascus purpureus Went and its related Chinese patent medicine and preparation, including double-armed trials (n = 18), single-armed trials (n = 6), three-armed trials (n = 3), and multiple-armed trials (n = 1). One study was set up with a blank control, and four were set up with a placebo. The mode of administration was oral. Patient sources included tertiary hospitals (n = 19), secondary hospitals (n = 7), and other sources (n = 2). Diseases included dyslipidemia (n = 22), carotid atherosclerotic plaque (n = 3), unstable angina (n = 2), abnormal liver function (n = 2), hyperglycemia (n = 1), type 2 diabetes (n = 1), uremia (n = 1), and fatty liver (n = 1).

Among them, 19 studies examined the effects of Chinese patent medicines and preparations related to Monascus purpureus Went, including Xuezhikang capsule (n = 6), Zhibituo capsule (n = 2), Shengqu Monascus purpureus Went capsule (n = 2), lipid-lowering Monascus purpureus Went micro-powder (n = 2), Monascus purpureus Went compound preparation (n = 1), compound Monascus purpureus Went capsule (n = 1), Monascus purpureus Went capsule for reducing sugar (n = 1), Monascus purpureus Went flavonoid tablet (n = 1), rattan Monascus purpureus Went soft capsule (n = 1), Danxi Monascus purpureus Went wine (n = 1), and C. chinensis Franch. Monascus purpureus Went medicine (n = 1); nine studies determined the clinical therapeutic effect of TCM Monascus purpureus Went.

Among them, the most commonly used dose of TCM Monascus purpureus Went was 6 g/dose, administered once daily, with a treatment course of 90 days; the most commonly used dose of Xuezhikang capsule was 2 capsules/dose, administered twice daily, and the course of treatment was 56 days; the most commonly used dose of Zhibituo capsule was 1.05 g/dose, administered thrice daily, with a treatment course of 60 or 90 days; the most commonly used dose of Shengqu Monascus purpureus Went capsule was 2 capsules/dose or 4 capsules/dose, and the course of treatment was 84 or 168 days; and the most commonly used dose of lipid-lowering Monascus purpureus Went micro-powder was 1 capsule/dose, administered thrice daily, with a treatment course of 50 or 180 days.

In terms of indicator domains, physical and chemical testing indicators were applied 28 times, symptom and sign indicators were applied 13 times, and TCM symptom/syndrome indicators were applied six times.

For counting indicators, clinical efficacy was applied 14 times, and TCM evidence efficacy was applied four times. Measurement indicators included lipid levels (n = 25), liver and kidney functions (n = 6), blood routine (n = 2), TCM evidence points (n = 2), blood glucose levels (n = 2), body mass index (n = 2), serum inflammatory factor (n = 2), electrocardiography (n = 1), SGA scores (n = 1), and carotid ultrasound (n = 1). The specific information on clinical trials is presented in Table 4.

A total of 21 studies were randomized controlled trials (79%), and six were self-controlled trials (21%). Among the 22 randomized controlled trials, only 15 reported “randomization”; six used a randomized numeric table method, and one used lottery method. Only one study performed allocation concealment, four studies blinded patients, and one study blinded outcome assessors. The remaining studies did not perform allocation concealment or apply blinding; no missing data were reported. Thirteen studies exhibited other sources of bias, such as not reporting the source of funding or trial enrollment, while nine studies provided complete reporting. The risk of bias assessment of clinical trials is presented in Table 5.

4 Discussion and analysis

4.1 Content determination method of active ingredients in Monascus purpureus Went

4.1.1 High-performance liquid chromatography

HPLC is the most commonly used method to determine the content of active ingredients in Monascus purpureus Went, particularly lovastatin and citrinin (orange mold) (Wang and Gao, 2006; Wen et al., 2011; Hao et al., 2017; Tan et al., 2015; Qiu et al., 2012; Luo et al., 2003; Zhang et al., 2016; Lu et al., 2019; Zhang et al., 1997; Liu, 2007; Fan, 2013; Zhang et al., 2001; Chen and Zhao, 2007; Zhu et al., 2023; Huang, 2000; Chen et al., 2008; Wang, 2014; Gao et al., 2022; Li et al., 2011; Wang, 2000; Song et al., 1999b; Xie et al., 2010; Huang et al., 2014; Wang et al., 2020; Li and Li, 2008; Lv et al., 2020; Li et al., 2010; Li et al., 2019; Qi et al., 2021), and is characterized by simplicity, accuracy, reliability, good repeatability, and high sensitivity.

4.1.2 Thin-layer chromatography scan

TLCS is a method used to determine the content of phosphatidylcholine and daidzein in Monascus purpureus Went and Xuezhikang capsule (Xu et al., 2000; Xu et al., 2001), which is characterized by simplicity and good repeatability and can be used to control the quality of Monascus purpureus Went and its preparations.

4.1.3 Capillary electrophoresis

CE is a method used to determine the contents of lovastatin and citrinin (a compound produced by orange mold) in Monascus purpureus Went (Chen et al., 2007a; Zhang et al., 2008), which is characterized by simplicity, speed, high sensitivity, and good repeatability in detecting certain charged components.

4.1.4 Other methods

AA is a method used to determine the content of amino acids in Monascus purpureus Went (Chen et al., 2007b), which is characterized by high sensitivity and accuracy. GC is a method used to determine the contents of oleic acid and linoleic acid in Monascus purpureus Went (Zhang et al., 2010). QuEChERS-UPLC-MRM-IDA Criteria-EPI is a method used to determine and quantify the content of lovastatin (Wang, 2016). PSA, ASA, and DNS are methods used to determine the content of polysaccharides in Monascus purpureus Went (Fang et al., 2021). FAAS is a method used to determine the content of metal trace elements in Monascus purpureus Went (Lin et al., 2001). SPSS PCA and SPSS CA were used to analyze trace elements in Monascus purpureus Went (Cao and Wu, 2009) to reveal the relationships and distribution patterns between components.

4.2 Chemical ingredients of Monascus purpureus Went

A variety of active ingredients in Monascus purpureus Went provide the material basis for the pharmacological effect of Monascus purpureus Went, mainly including Monascus pigment, monacolin K, ergosterol, stigmasterol, Monascus purpureus Went polysaccharide, and a variety of enzymes.

4.2.1 Monascus pigment

Monascus pigment is a secondary metabolite of Monascus purpureus Went. Monascus pigment not only provides a unique color for Monascus purpureus Went but also possesses physiological activities such as antioxidant, antibacterial, and anti-inflammatory properties. So far, as many as 54 types of Monascus pigment have been identified, among which the more intensively studied pigments include yellow Monascus pigment, ankaflavin, rubropunctamine, and monascorubramine. It has been demonstrated that yellow Monascus pigment has a protective effect on the liver of hyperlipemia mice and can regulate blood lipids, and the mechanism of action may be related to the regulation of lipid metabolism and activation of the AMP-activated protein kinase (AMPK) pathway to stimulate fatty acid oxidation (Fang et al., 2021). Monascorubramine can promote the apoptosis of gastric cancer AGS cells, while no obvious inhibitory effect on normal cells was observed, and its therapeutic coefficient is higher than that of paclitaxel, which is a conventional chemotherapeutic drug for gastric cancer (Lin et al., 2001). The safety of Monascus pigment has been proven to be high through acute and chronic toxicity studies, and it has been widely used as an additive ingredient of Monascus pigment in food and cosmetic production processes (Jiang et al., 2021; Xu et al., 2018; Pan et al., 2023).

4.2.2 Statin ingredients

The statin component of Monascus purpureus Went has a wide range of applications in the field of medicine. In the late 1970s, Japanese scientists discovered and isolated a chemical component called monacolin K from the fermentation of Monascus purpureus Went, which can inhibit cholesterol synthesis in the body (Kong et al., 2005). Further studies revealed that the statin component in Monascus purpureus Went is similar to chemically synthesized statins in terms of its lipid-lowering effect. Among them, lovastatin, the most common statin component in Monascus purpureus Went, was formally approved by the FDA in the United States in 1987 and became the first generation of statin lipid-lowering drugs. In addition, lovastatin has an anti-tumor effect, which can induce the activation of the key molecule of apoptosis, caspase 7, and its receptor PARP protein cleavage. Lovastatin can inhibit the proliferation of PC3 cells and induce apoptosis in prostate cancer and has been shown to be efficacious in common tumors, such as gastric cancer, carcinoma of the bile duct, and nasopharyngeal carcinoma (NPC) (Xu et al., 2018).

4.2.3 Sterol composition

Monascus purpureus Went produces a variety of sterol components during the fermentation process, such as ergosterol and stigmasterol. Ergosterol is one of the precursor substances of vitamin D2, which can be converted into vitamin D2 after ultraviolet irradiation, and is involved in the metabolism of calcium and phosphorus in the body, which has an obvious effect on the prevention and treatment of rickets in infants and young children and the promotion of calcium and phosphorus absorption in pregnant women and the elderly. Studies have shown that ergosterol can significantly reduce the blood glucose level of diabetic nephropathy model mice, providing a theoretical basis for ergosterol to be used in the clinical treatment of diabetic nephropathy (Xu et al., 2018). Soysterol can competitively inhibit the absorption of cholesterol in the human body and effectively reduce the level of serum cholesterol, which is an important active ingredient in regulating lipid balance and preventing cardiovascular and cerebrovascular diseases (Ge et al., 2012).

4.2.4 Other ingredients

Monascus purpureus Went contains a variety of other active ingredients, such as Monascus purpureus Went polysaccharide, unsaturated fatty acids, a variety of enzymes (e.g., amylase, protease, and lipase), and flavonoids, which also play important roles in the pharmacological effects of Monascus purpureus Went.

For example, Monascus purpureus Went polysaccharides exhibit various physiological activities, such as immunoregulatory, anti-tumor, and lipid-lowering effects; unsaturated fatty acids help lower blood lipids and prevent cardiovascular diseases; and a variety of enzymes promote digestion and absorption of food in the human body.

4.3 Pharmacological mechanism of action of Monascus purpureus Went

4.3.1 Lipid-lowering ability

Monascus purpureus Went has a lipid-lowering effect. This is mainly attributed to the enrichment of statins in Monascus purpureus Went, such as monacolin K, which is the active ingredient of lovastatin. A number of included clinical trials have shown (Yin et al., 2016; Zhang and He, 2016; Chen et al., 2021; Luo and Zhong, 2020; Zhang et al., 2020; Zhao et al., 2018; Shi et al., 2015; Gao et al., 2016) that Monascus purpureus Went has a lipid-lowering effect, generally reducing plasma total cholesterol (TC) levels, low-density lipoprotein (LDL) levels, and triglyceride (TG) levels and also increasing high-density lipoprotein (HDL) levels.

4.3.2 Oxidation resistance

Antioxidant components such as polyphenolic compounds and flavonoids in Monascus purpureus Went can scavenge free radicals in the body and reduce cellular damage caused by oxidative stress. Studies have shown that the extracellular polysaccharides of Monascus purpureus Went have the ability to scavenge DPPH-free radicals, confirming the antioxidant effect of Monascus purpureus Went (Cai et al., 2010). This antioxidant effect helps slow down the cellular aging process and protects the cardiovascular system, the liver, and other organs from oxidative damage. In addition, the antioxidant effect of Monascus purpureus Went is complemented by its lipid-lowering effect, which works together to maintain the healthy state of the human body. Included clinical trials have shown that Monascus purpureus Went can reduce ALT and AST levels in patients with hyperlipemia and liver function abnormalities, thus protecting the liver.

4.3.3 Anti-inflammatory action

Monascus purpureus Went has an anti-inflammatory effect, which is closely related to the various anti-inflammatory components it contains. Polyphenols and flavonoids in Monascus purpureus Went have antioxidant and free-radical scavenging ability, which can reduce the inflammatory response caused by oxidative stress. Studies have shown that Monascus purpureus Went can reduce serum TNF-α and CRP levels in inflammatory mouse models, confirming the anti-inflammatory effect of Monascus purpureus Went (Wang et al., 2006a; Wang et al., 2008), which makes Monascus purpureus Went potentially useful in the treatment of non-infectious inflammatory diseases, such as arthritis and dermatitis.

4.3.4 Anti-tumor activity

In recent years, important progress has also been made in research on the anti-tumor effects of Monascus purpureus Went. Monascus purpureus Went polysaccharides and Monascus pigments in Monascus purpureus Went have an effect on inhibiting the growth and proliferation of tumor cells. These components affect the metabolism and signal transduction pathway of tumor cells through different pathways, thus exerting an anti-tumor effect. By determining the tumor inhibition rate, relative growth rate, and index of each organ in loaded mice, it was found that erythrocyte extracellular polysaccharides had a tumor-inhibitory effect on H22-loaded mice in vivo (Zhou et al., 2011). The determination of body weight, tumor weight, tumor suppression rate, and changes in spleen weight and spleen index of the loaded mice indicated that Monascus purpureus Went polysaccharides had a good inhibitory effect on tumor growth in loaded mice (Ding, 2007). Although the application of Monascus purpureus Went in anti-tumor therapy is still in the research stage, its potential should not be ignored.

4.4 Methodological quality

4.4.1 Methodological quality of animal studies

The methodological quality assessment of animal studies related to Monascus purpureus Went found that most studies only reported “randomization,” while a few used the random number table. Assignment concealment and blinding of investigators or animal handlers and evaluators of results were not reported in most studies, which may have led to subjective bias in the expected experimental results, and only a few used assignment concealment and blinding. A number of studies did not report the randomization of the environment in which the animals were placed, which may have influenced objective environmental factors such as temperature, humidity, and light intensity in different locations on the experimental results. The result data were completely reported. In conclusion, it is necessary to improve the generation of random allocation sequences, allocation concealment, application of blinding, and randomness of the environment in animal studies related to Monascus purpureus Went.

4.4.2 Methodological quality of clinical trials

The methodological quality assessment of clinical trials related to Monascus purpureus Went found that most trials only reported “randomization,” while a few used the random number table and lottery. Assignment concealment and blinding of patients and outcome evaluators were not reported in most trials, which may increase the risk of measurement bias and evaluator bias, and only a few used assignment concealment and blinding. Some trials did not report registration and conflict of interest, which could lead to inappropriate influence from sponsors. Outcome data were completely reported. In conclusion, it is necessary to improve the generation of random allocation sequences, allocation concealment, application of blinding, and reporting of funding sources in clinical trials related to Monascus purpureus Went.

4.4.3 Suggestion for the study design

The common problems of methodological quality deficiencies in both animal studies and clinical trials are obvious, and the following suggestions are made: first, it is suggested that suitable random sequence generation methods, such as the random number table method, should be used to ensure the randomness and fairness of the allocation process. Second, it is suggested that allocation concealment and application of the double-blind method, including blinding of operators and observers, should be implemented. The person in charge of the operation should not know which group each patient is assigned to, in order to eliminate operator-induced subjective bias in the results. The person responsible for data collection and analysis should also not know the specific group to which each patient is assigned. The process of data collection and analysis should be carried out independently to ensure the objectivity and accuracy of the results. In addition, it is suggested that other conditions (e.g., environment and operation) should be strictly controlled for consistency during the study to ensure the reliability and repeatability of results. Finally, during data analysis, care should be taken to control the effect of confounding factors and other biases and to report in detail on the source of funding and registration to ensure the objectivity and accuracy of the results.

4.5 Limitation

There are some limitations to this review. First, the English-language literature obtained from the search was relatively limited. Second, the studies mainly focus on molecular and animal studies, with relatively few clinical trials. Third, some of the studies are of poor quality, and the reference value of their results may therefore be limited. Fourth, excluding studies for which the full texts could not be obtained may lead to data bias. Fifth, some of the clinical trials contained partially unreported information about the subjects, such as the patient source, enrollment time, and age range, which may reduce the strictness of the study. Sixth, only two meta-analyses were obtained and assessed for methodological quality and reporting standards in this study, and the results showed that they were of low quality, but due to their small number, these studies were not examined and described in detail in order to avoid study bias. The assessment of methodological quality and reporting standards for meta-analyses are presented in Supplementary Adds S2, S3.

4.6 Research implications

4.6.1 Clinical safety

Existing studies have shown that the contraindications for Monascus purpureus Went productions mainly include the following: ① patients allergic to monacolin K/lovastatin or any excipients; ② patients with acute liver disease; ③ patients with severe renal impairment (eGFR <30 mL/min); ④ patients with various myopathies; and ⑤ pregnant women, lactating women, and women of childbearing age who have not taken effective contraceptive measures (Banach et al., 2022). It is recommended that its importance be emphasized in clinical practice.

4.6.2 Fundamental research challenges

In terms of the bioactive ingredient biosynthetic pathways and regulatory mechanisms of substances produced during Monascus fermentation, the current challenges in the development of Monascus purpureus Went include improving the content of active ingredients like lovastatin and controlling the content of toxic metabolites like citrinin through methods such as optimizing fermentation parameters, mutagenic breeding, and genetic engineering.

4.6.3 Other suggestions

More contamination risks derive from raw materials, microbial metabolism, or processing errors; the suggestions for the production quality control of Monascus purpureus Went are as follows: first, the quality control of raw materials should be optimized, the standardized management of fermentation strains should be strengthened, and high-quality fermentation strains should be accurately identified and screened. Second, the quality detection standard system should be improved, the specifications for the determination of active ingredient contents should be clarified, and the detection scope of safety indicators should be expanded. Third, the production process system must be optimized, the operation process must be standardized, fermentation parameters must be improved, and fermentation conditions must be strictly controlled. Fourth, the construction of the regulatory system must be improved, mandatory third-party safety reviews must be implemented, and the post-market supervision of products must be strengthened.

To promote the high-quality development of Monascus purpureus Went studies, the suggestions are as follows: first, standards should be set up. Unified quality standards for experimental design and efficacy evaluation should be developed to improve comparability between different studies. The production process and quality control of Monascus purpureus Went should be standardized to ensure the stable quality of Monascus purpureus Went products used in research and application. Second, multidisciplinary cooperation should be promoted. Experts in the fields of pharmacy, medicine, biology, and other multidisciplinary fields should be encouraged to cooperate in the studies and explore the pharmacological action mechanism of Monascus purpureus Went in depth from different perspectives. Third, the research and development of new drugs should be encouraged. Modern preparation technology should be actively used to develop new Monascus purpureus Went preparations with more stable efficacy. Fourth, more research on the combination of Monascus purpureus Went and other drugs should be encouraged to observe the therapeutic effect and safety. Fifth, human pharmacokinetic studies and clinical trials should be performed to explore the effective dosage range of Monascus purpureus Went products, validate safety and prevent adverse events, and provide evidentiary support for clinical practice. Concurrently, key procedures, including ethical review and informed consent, must be strictly implemented throughout the process.

5 Conclusion

As a type of traditional Chinese medicine, the pharmacological action mechanism of Monascus purpureus Went is extensive and complex. Given the extensive global use of Monascus purpureus Went products, we have gradually revealed its mechanism of action in regulating blood lipids and exerting anti-inflammatory, anti-oxidant, and anti-tumor effects through modern science research and technology. Moreover, we also need to pay attention to the contraindications and safety issues associated with the use of Monascus purpureus Went to ensure its safety and effectiveness in our daily lives.

References

• 1

  BanachM.CatapanoA. L.CiceroA.EscobarC.FogerB.KatsikiN. (2022). Red yeast rice for dyslipidaemias and cardiovascular risk reduction: a position paper of the International Lipid Expert Panel. Pharmacol. Res.183, 106370. 10.1016/j.phrs.2022.106370

  • CrossRef
  • Google Scholar

• 2

  CaiQ.ShenB.ZhangH.ChengD. (2010). Extraction of extracellular polysaccharides from Fermentum Rubrum and determination of antioxidant activity. Chin. Arch. Tradit. Chin. Med.28 (03), 598–600. 10.13193/j.archtcm.2010.03.151.caiq.067

  • CrossRef
  • Google Scholar

• 3

  CaoH.WuQ. (2009). Principal component analysis and cluster analysis for the study of trace element content in traditional Chinese medicine Fermentum Rubrum. J. Southwest Univ. Natl. Nat. Sci. Ed.35 (04), 789–792.

  • Google Scholar

• 4

  CaoH.ZhuJ.YangC.WangR. (2007). Observation on the therapeutic effect of Fermentum Rubrum capsule for reducing sugar on type 2 diabetes. Int. J. Tradit. Chin. Med.29 (05), 307–308.

  • Google Scholar

• 5

  ChenJ.LiZ.QiW.LiuZ.LiB. (2007a). High performance capillary electrophoresis analysis method for detecting the content of hesperidin in traditional Chinese medicine Fermentum Rubrum. China J. Chin. Mater. Med.14, 1412–1415.

  • Google Scholar

• 6

  ChenJ.LiZ.QiW.LiuZ.LiB. (2008). Determination of citrine in fermentum Rubrum by RP HPLC. West China J. Pharm. Sci. (02), 219–220. 10.13375/j.cnki.wcjps.2008.02.026

  • CrossRef
  • Google Scholar

• 7

  ChenL.ChenT.WuJ. (2007b). Analysis of amino acid composition in Fermentum Rubrum. Str. Pharm. (02), 53–55.

  • Google Scholar

• 8

  ChenL.ZhangS.DengY.LiuH. (2021). Clinical observation of the combination treatment of hyperlipidemia and abnormal liver function with Fermentum Rubrum. Liaoning J. Tradit. Chin. Med.48 (07), 104–107. 10.13192/j.issn.1000-1719.2021.07.029

  • CrossRef
  • Google Scholar

• 9

  ChenW.LiuF. (2015). Clinical observation on the effect of dietary therapy with Danxi Fermentum Rubrum liquor on lowering blood lipids and blood sugar. China Naturop.23 (10), 77–78. 10.19621/j.cnki.11-3555/r.2015.10.063

  • CrossRef
  • Google Scholar

• 10

  ChenX.ZhaoJ. (2007). Determination of monacolin K in Fermentum Rubrum by high performance liquid chromatography. Chem. Bioeng. (Wuhan. China) (12), 74–75+78.

  • Google Scholar

• 11

  ChenY.ChenC.ZhangS. (2005). Effect of Lovastatin from Red Kojic on lipid metabolism and expression of lipoprotein lipase mRNA in hyperlipidemic mice. Chin. Tradit. Herb. Drugs.36 (5). 10.3321/j.issn:0253-2670.2005.05.032

  • CrossRef
  • Google Scholar

• 12

  ChenY.PengD.TianH. (2000). Research and application of Fermentum Rubrum and Aspergillus spp. J. Hubei Agric. Coll.20 (2).

  • Google Scholar

• 13

  ChenY.ZhangG.YeZ. (2010). Study on the lipid-lowering effect of compound Fermentum Rubrum extract on hyperlipidemic rats. China J. Chin. Mater. Med.35 (04), 504–507. 10.4268/cjcmm20100422

  • CrossRef
  • Google Scholar

• 14

  CuiC.ZhouK.YangL.ZhaiY.QiX. (2002). Clinical observation on the treatment of 45 cases of hyperlipidemia with compound Fermentum Rubrum capsule. Chin. Tradit. Pat. Med. (02), 31–34.

  • Google Scholar

• 15

  DingH. (2007). Preliminary study on the anti-tumor effect of Fermentum Rubrum polysaccharides. J. Fungal Res. (03), 171–173. 10.13341/j.jfr.2007.03.012

  • CrossRef
  • Google Scholar

• 16

  DingY.RenH. (2023). The lipid-lowering effect of Fermentum Rubrum earthworm protein tablet on hyperlipidemic rats. Ind. Microbiol. (Shanghai, China)53 (04), 104–106.

  • Google Scholar

• 17

  DuX.ChenY. (2013). Study on the acute toxicity and mutability of Fermentum Rubrum extract. Food Res. Dev. (Tianjin, China)34 (05), 4–6+30.

  • Google Scholar

• 18

  EndoA. (1980). Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. J. Antibiot. (Tokyo)33 (3), 334–336. 10.7164/antibiotics.33.334

  • CrossRef
  • Google Scholar

• 19

  FanW. (2013). Determination of lovastatin content in Fermentum Rubrum by high performance liquid chromatography. J. Mod. Med. Health.29 (16), 2417–2419+2421.

  • Google Scholar

• 20

  FangJ.WangC.WangL.ShiW.GuoY.LiY.et al (2021). Comparative study on the determination methods of polysaccharide content in Fermentum Rubrum Fuling tablets. Lishizhen Med. Mater. Med. Res.32 (11), 2672–2676.

  • Google Scholar

• 21

  GaoS.HuangC.HeZ. (2015). Study on the weight loss and lipid-lowering effects of Fengfengtongsheng powder combined with Fermentum Rubrum. Asia Pac. Tradit. Med.11 (24). 10.11954/ytctyy.201524005

  • CrossRef
  • Google Scholar

• 22

  GaoW.LinY.DaiG.ZhaoL. (2022). Simultaneous determination of adenosine and three other components in Fermentum Rubrum from different sources by HPLC method. Pharm. Clin. Res.30 (02), 140–142. 10.13664/j.cnki.pcr.2022.02.022

  • CrossRef
  • Google Scholar

• 23

  GaoY.YuC.YanG.LinX.LuF.ShenJ. (2016). Observation of the therapeutic effect of functional Fermentum Rubrum on hyperlipidemia. Front. Med.6 (18).

  • Google Scholar

• 24

  GeF.WangY.WangJ.YuH.LiC. (2012). Research on the main active components in Fermentum Rubrum. J. Kunming Univ. Sci. Technol. Nat. Sci.37 (02), 61–64.

  • Google Scholar

• 25

  HaoS.WangL.LiH.ZhangD.XuH. (2017). Simultaneous determination of lovastatin and lovastatin acid in Fermentum Rubrum and Zhibituo tablets by QAMS. Chin. J. Exp. Tradit. Med. Formulae.23 (5). 10.13422/j.cnki.syfjx.2017050074

  • CrossRef
  • Google Scholar

• 26

  HeS.LouX.ZhangR.XuJ. (2007). Observation on the clinical effect of Fermentum Rubrum Flavonoids tablets in regulating blood lipids. Chin. Prev. Med. (03), 284–286.

  • Google Scholar

• 27

  HeY. (2004). Effect of fermented extract of Fermentum Rubrum garlic on hyperlipemia and arteriosclerosis lesions in cholesterol-loaded rabbits. Int. J. Tradit. Chin. Med. (06), 347–348.

  • Google Scholar

• 28

  HuangH. (2000). Separation and determination of lovastatin in Fermentum Rubrum by HPLC method. Str. J. Prev. Med. (04), 40–41.

  • Google Scholar

• 29

  HuangP.ZhangR. (2005). Influence of Xue Zhi Kang on C-reaction albumen of early plasma in unstable colic patients. Chin. Med. Mod. Disrance Educ. China.3 (12). 10.3969/j.issn.1672-2779.2005.12.022

  • CrossRef
  • Google Scholar

• 30

  HuangX.ChenP.ChenL.HuY. (2014). Determination of Monacolin K content in water soluble Fermentum Rubrum by HPLC method. Zhejiang J. Tradit. Chin. Med.49 (09), 685–686.

  • Google Scholar

• 31

  HuangY.ZhouD.YuQ. (2019). Research on the auxiliary lipid-lowering function of Fermentum Rubrum propolis tablets. Food Res. Dev. (Tianjin, China)40 (08), 195–199.

  • Google Scholar

• 32

  JiangL.LiS.LiuZ.HaoZ.HeJ. (2008). Effect of Fermentum Rubrum and grape seed anthocyanidin mixture on blood lipid in atherosclerotic rats. Food Sci. (Beijing, China) (07), 420–423.

  • Google Scholar

• 33

  JiangY.DongY.ZhouF.ChenJ.ZhouY.TianC.et al (2021). Research progress on chemical composition, pharmacological effects and clinical applications of Fermentum Rubrum. Chin. Tradit. Herb. Drugs52 (23), 7379–7388.

  • Google Scholar

• 34

  KongY.LiuL.WuM. (2005). Research progress on lipid-lowering Fermentum Rubrum at home and abroad. Heilongjiang J. Tradit. Chin. Med. (06), 56–57.

  • Google Scholar

• 35

  LeiP.GuoJ.JinZ. (2007). Biochemical mechanism of Fermentum Rubrum in reducing blood pressure in renal vascular hypertension rats. J. Liaoning Univ. Tradit. Chin. Med. (03), 217–218. 10.13194/j.jlunivtcm.2007.03.219.leip.147

  • CrossRef
  • Google Scholar

• 36

  LiG.LiH. (2008). Determination of lovastatin in fermentation broth of Monascus by HPLC. Guangdong Pharm. J.24 (3).

  • Google Scholar

• 37

  LiX.XueL.ZhouL.DuanZ.GuoS. (2011). HPLC method for detecting kumquat in Xuezhikang capsule. China Pharm. (Wuhan. China)14 (08), 1088–1090.

  • Google Scholar

• 38

  LiY.ZhangC.YangY.ChenZ. (2019). HPLC determination of seven nucleoside components in Fermentum Rubrum. China Med. Her.16 (12), 101–104.

  • Google Scholar

• 39

  LiY.ZhangX.QinM. (2010). HPLC method for determination of Monacolin K, Monacolin K, and dehydromonacolin K in functional Fermentum Rubrum extract. Chin. Tradit. Herb. Drugs.41 (08), 1286–1288.

  • Google Scholar

• 40

  LinP.XingW.MiH.WangX.WuH. (2001). Determination of trace elements in the Chinese traditional medicine--Red Kojic by flame atomic absorption spectrophotometry. Pharm. Care Res.1 (1). 10.3969/j.issn.1671-2838.2001.01.014

  • CrossRef
  • Google Scholar

• 41

  LinX.ZhouY.XuM.LinX.ShaoS.ZhuX.et al (2014). The effect of traditional Chinese medicine Fermentum Rubrum on the expression of PPAR γ and adiponectin receptor in hyperlipidemic rats. Zhejiang Med. J.36 (21), 1767–1770.

  • Google Scholar

• 42

  LiuJ.ZhangJ.LiuX.ZhangR.LeN.ZhangS.et al (2020). Exploring the effect of Fermentum Rubrum Fuling tablets on rats with spleen deficiency and dampness excess hyperlipidemia based on the theory of dialectical health care. Glob. Tradit. Chin. Med.13 (11), 1837–1845.

  • Google Scholar

• 43

  LiuL.WuM.WangH.ZhangW. (2011). A randomized controlled study of lipid lowering Fermentum Rubrum micro powder in the treatment of dyslipidemia with carotid atherosclerosis. Chin. J. Integr. Tradit. West. Med. Chin. Ed.31 (09), 1196–1200.

  • Google Scholar

• 44

  LiuX. (2007). Determination of lovastatin content in Xuezhikang soft capsules by high performance liquid chromatography. Jiangxi J. Tradit. Chin. Med.38 (7). 10.3969/j.issn.0411-9584.2007.07.054

  • CrossRef
  • Google Scholar

• 45

  LiuY.PengL.HuC. (2021). Study on the lipid regulating efficacy and safety of Ginkgo Fermentum Rubrum vitamin formula. New Chin. Med.52 (07), 508–512.

  • Google Scholar

• 46

  LiuY.WuM.HuY.WangX.DingK. (2019). The effect of Fermentum Rubrum flavins on blood lipids and liver AMPK α ACC, PPAR - α, and CPT1 protein expression in hyperlipidemic rats. Chin. J. Tradit. Med. Sci. Technol.26 (03), 351–356.

  • Google Scholar

• 47

  LiuZ.LaiW.LiuD.MeiS.FuY. (2013). Study on the lipid-lowering effect of compound Fermentum Rubrum capsules in rats. J. Food Saf. Qual.4 (03), 819–822. 10.19812/j.cnki.jfsq11-5956/ts.2013.03.029

  • CrossRef
  • Google Scholar

• 48

  LiuZ.WangX.ZhaoK. (1998). Clinical observation of Zhibituo in the treatment of 76 cases of hyperlipidemia. Mod. J. Integr. Tradit. Chin. West. Med. (02), 194–195.

  • Google Scholar

• 49

  LuJ.LuY.JinH.XuX.ShenJ.RenJ.et al (2017). The effect of Fermentum Rubrum on serum ALP, TRAP, and bone tissue TNF - α, RANK expression in osteoporotic rat model after ovariectomy. Chin. J. Tradit. Med. Traumatol. Orthop.25 (09), 5–8.

  • Google Scholar

• 50

  LuJ.QianX.HuaJ.HuaW.ZhuX. (2008). The effect of Fermentum Rubrum on inducing differentiation of rat bone marrow stromal cells into osteoblasts. China J. Tradit. Chin. Med. Pharm. (2005-) (06), 541–544.

  • Google Scholar

• 51

  LuJ.WangW.ChenB. (2006). Effect of Fermentum Rubrum on proliferation, differentiation and mineralization function of osteoblasts in vitro. Chin. J. Tradit. Med. Traumatol. Orthop. (02), 41–45.

  • Google Scholar

• 52

  LuJ.WangW.WuC.YangL.WangJ. (2005b). Correlation study of Fermentum Rubrum on bone mineral density and bone mechanics changes in rats. Zhejiang J. Integr. Tradit. West. Med. (09), 529–531.

  • Google Scholar

• 53

  LuJ.WuC.NiG.WangW.WangJ. (2005a). Fermentum Rubrum versus ovariectomized rats BMP experimental studies of expression and osteoblast proliferation. China J. Orthop. Traumatol. (01), 29–31.

  • Google Scholar

• 54

  LuJ.WuC.WangW.WangJ.YangL. (2004). Effect of Fermentum Rubrum on serum hormone levels, bone density, and bone biomechanics in castrated rats. Chin. J. Tradit. Med. Traumatol. Orthop. (04), 22–25.

  • Google Scholar

• 55

  LuS.YuQ.Si-tuY. (2016). Protective effect of red yeast rice capsule containing coenzyme Q10 on osteoporosis in rats induced by ovariectomy combined with D-galactose. Chin. Pharmacol. Bull.32 (9). 10.3969/j.issn.1001-1978.2016.09.013

  • CrossRef
  • Google Scholar

• 56

  LuS.ZhangL.HeX.DingH.WuT. (2019). Determination of lovastatin and coenzyme Q_ (10) in functional Fermentum Rubrum powder. Guangzhou Chem. Ind.47 (18), 92–95.

  • Google Scholar

• 57

  LuX.HuY.WangX.GaoS. (2012). Clinical observation of Xuezhikang in the treatment of hyperlipidemia. Hubei J. Tradit. Chin. Med.34 (09), 38–39.

  • Google Scholar

• 58

  LuoH.ZhongZ. (2020). The effect of Tibetan Fermentum Rubrum on blood lipids in patients with dyslipidemia. China Naturop.28 (16), 57–59. 10.19621/j.cnki.11-3555/r.2020.1628

  • CrossRef
  • Google Scholar

• 59

  LuoJ.SunQ.MaZ.HeZ.LiX. (2019). The gastrointestinal regulatory effects of fermented Fermentum Rubrum on mice with spleen deficiency and food accumulation syndrome before and after processing. Chin. J. Exp. Tradit. Med. Formulae.25 (22), 108–114. 10.13422/j.cnki.syfjx.20192252

  • CrossRef
  • Google Scholar

• 60

  LuoR.SunK.XieS.HanY.ZhaoY. (2003). Method for determining the total amount of lovastatin in Fermentum Rubrum. J. Hyg. Res.32 (02), 157–158.

  • Google Scholar

• 61

  LuoW.ZhangQ. (2011). Tissue and biochemical study of Fermentum Rubrum improving non alcoholic fatty liver in rats. Chin. J. Gen. Pract.9 (12), 1842–1843+1853. 10.16766/j.cnki.issn.1674-4152.2011.12.012

  • CrossRef
  • Google Scholar

• 62

  LuoW.ZhangQ.LvZ. (2010). Study on the mechanism of Fermentum Rubrum improving insulin resistance in non-alcoholic fatty liver disease in rats. Tradit. Chin. Drug Res. Clin. Pharmacol.21 (04), 375–378. 10.19378/j.issn.1003-9783.2010.04.014

  • CrossRef
  • Google Scholar

• 63

  LvS.HeX.ZhangL.DingH.WuT. (2020). Determination of lovastatin content in Fermentum Rubrum capsules by HPLC method. Str. Pharm.32 (03), 63–66.

  • Google Scholar

• 64

  MaH.GaoM.LiX.ZhaoW.YingY. (2022). Genetic toxicity evaluation of Sanqi Fermentum Rubrum compound preparation. Food Drug24 (01), 21–25.

  • Google Scholar

• 65

  MaY. (2025). “The Kobayashi Pharmaceutical scandal in Japan continues to ferment,” in Guangming Dly. Guangming Dly. 008.

  • Google Scholar

• 66

  Ou-yangZ.LiY.LiangG.JinH.KangD. (2012). The effect of buckwheat Fermentum Rubrum on blood lipid levels in experimental hyperlipidemic rats. J. Yanbian Med. Coll.35 (01), 25–27. 10.16068/j.1000-1824.2012.01.008

  • CrossRef
  • Google Scholar

• 67

  PanR.FangZ.TangX.ZhengL.WangD. (2023). Research progress on secondary metabolites and pharmacological effects of Monascus purpureus. West China J. Pharm. Sci.38 (03), 345–351. 10.13375/j.cnki.wcjps.2023.03.024

  • CrossRef
  • Google Scholar

• 68

  PangZ.LiP.HuangY.LiuY.JiangY. (2017). The animal experimental study of Natto-monascus on hyperlipidemia. Mod. Food.7 (14). 10.16736/j.cnki.cn41-1434/ts.2017.14.028

  • CrossRef
  • Google Scholar

• 69

  QiF.RenD.HuangZ.QinL.ZhuB. (2021). Determination of lovastatin and citrine in Fermentum Rubrum from 16 production areas. Chin. Tradit. Pat. Med.43 (04), 948–953.

  • Google Scholar

• 70

  QianS.WangY.YeY. (2015). The effect of alcohol extracted Fermentum Rubrum on BMP-4 mRNA and protein expression during fracture healing in osteoporotic rats. Chin. J. Tradit. Med. Sci. Technol.22 (03), 284–286.

  • Google Scholar

• 71

  QiuL.HaoJ.GuanC. (1997). Observation on the treatment of 112 cases of hyperlipidemia with Fermentum Rubrum extract preparation. China Naturop. (06), 34. 10.19621/j.cnki.11-3555/r.1997.06.052

  • CrossRef
  • Google Scholar

• 72

  QiuW.LiuX.ZhengK.FuW. (2012). Immuno-affinity chromatographic purification: the study of methods to test citrinin in monascus products by high performance liquid chromatography. Chin. J. Prev. Med. (Beijing).46 (8), 750–753. 10.3760/cma.j.issn.0253-9624.2012.08.017

  • CrossRef
  • Google Scholar

• 73

  ShenJ.LuJ.XuX.JinH.RenJ.LuY.et al (2018). The effect of Fermentum Rubrum on the expression of RANKL, OPG protein and mRNA in bone tissue of ovariectomized rats. China J. Tradit. Chin. Med. Pharm. (2005-).33 (04), 1370–1372.

  • Google Scholar

• 74

  ShiM.ZhaoY.HuG.BaiH.LiuQ.ZhangJ. (2015). Clinical observation on the lipid-lowering effect of Fermentum Rubrumt tea drink on elderly patients. Pract. J. Med. Pharm.32 (04), 328–329. 10.14172/j.cnki.issn1671-4008.2015.04.015

  • CrossRef
  • Google Scholar

• 75

  SongH.MiH.GuoT. (1999a). Research progress of traditional Chinese medicine Fermentum Rubrum. J. Pharm. Pract. (03), 44–46.

  • Google Scholar

• 76

  SongH.MiH.GuoT.WuW.ChuW. (1999b). Determination of lovastatin in Hongqu from various sources by HPLC. Chin. Tradit. Herb. Drugs (2). 10.3321/j.issn:0253-2670.1999.02.009

  • CrossRef
  • Google Scholar

• 77

  SuS.LiuC.YinQ.LiH.LiuJ.ChengM. (2014). The effects of Xuezhikang on the functions of endothelial Progenitor cells isolated from experimental hyperlipidemic rats. Prog. Mod. Biomed.14 (36). 10.13241/j.cnki.pmb.2014.36.009

  • CrossRef
  • Google Scholar

• 78

  SunJ.SuH.LiaoX.GuiW.FangY.HanL.et al (2022). Exploring the mechanism of action of Fermentum Rubrum in treating cerebral small vessel disease based on network pharmacology and animal experiments. Cent. South Pharm.20 (02), 278–283.

  • Google Scholar

• 79

  SunJ. (2025). “Warning and Inspiration from the “Red Yeast Storm” at Kobayashi Pharmaceutical,” in Xinhua Dly. Telegraph. 004

  • Google Scholar

• 80

  SunM.LiY.YanW. (2001a). Study on the effect of Fermentum Rubrum on improving hemorheology in hyperlipidemic rats. J. Hyg. Res.30 (03), 173–175.

  • Google Scholar

• 81

  SunM.LiY.YanW. (2001b). Study on the effect of Fermentum Rubrum in lowering blood pressure. J. Hyg. Res.30 (4). 10.3969/j.issn.1000-8020.2001.04.006

  • CrossRef
  • Google Scholar

• 82

  TanY.MaY.LiuQ.WangW.HuangF. (2015). Research on the quality standards of Qingke Fermentum Rubrum. World Sci. Technol. Mod. Tradit. Chin. Med.17 (03), 614–619.

  • Google Scholar

• 83

  TangC.ChangH. (2012). The effect of Xuezhikang on blood lipids and hemorheology. Chin. Commun. Dr.14 (22). 10.3969/j.issn.1007-614x.2012.22.249

  • CrossRef
  • Google Scholar

• 84

  TangF.ZhangJ.ZouJ.SunW.JiaoX. (2004). Fermentum Rubrum Preliminary study on the antihypertensive effect of L-nitroarginine in hypertensive rats. Food Sci. (Beijing, China) (04), 155–157.

  • Google Scholar

• 85

  WangC. (2000). HPLC detection of lovastatin in functional Fermentum Rubrum. J. Beijing Univ. Agric. (02), 48–51. 10.13473/j.cnki.issn.1002-3186.2000.02.010

  • CrossRef
  • Google Scholar

• 86

  WangH.ZhouD.XuS.YeH. (2005). Experimental study on the effect of compound Fermentum Rubrum in regulating blood lipid. Chin. J. Health Lab. Technol. (05), 540–541.

  • Google Scholar

• 87

  WangJ. (2014). Simultaneous determination of two configurations of Lovastatin in Fermentum Rubrum by HPLC method. Zhejiang J. Integr. Tradit. West. Med.24 (03), 273–274.

  • Google Scholar

• 88

  WangJ.KangR.Ji-Le-TuH.LiangH.HongL.YanL.et al (2020). Determination of total lovastatin in hongmao medicinal wine. J. North. Pharm.17 (9). 10.3969/j.issn.1672-8351.2020.09.001

  • CrossRef
  • Google Scholar

• 89

  WangJ.WangX.ShiB. (2016). Observation on the therapeutic effect of Shengqu Fermentum Rubrum capsule on carotid atherosclerosis. Drug Eval. Res.39 (06), 1054–1057.

  • Google Scholar

• 90

  WangJ.YangB.WangX.ShiZ. (2014). Determination of treatment course and observation of efficacy of Shengqu Fermentum Rubrum capsules in the treatment of dyslipidemia. Drugs Clin.29 (08), 888–890.

  • Google Scholar

• 91

  WangL. (2019). Experimental study on the lipid-lowering effect of Fermentum Rubrum on high-fat rats. J. Cardiovasc. Surg. (Electron. Ed.)8 (04), 50–51.

  • Google Scholar

• 92

  WangL.TianY.MeiC. (2000). Effect of Fermentum Rubrum extract on serum lipid profile and glomerulosclerosis in nephrotic syndrome. Chin. J. Integr. Tradit. West. Nephrol. (03), 154–156.

  • Google Scholar

• 93

  WangQ.QiF.BaoB.SunQ. (2024a). Isolation and ITS molecular identification of high-yield Lovastatin producing purple Monascus purpureus. Chin. Pharm. J.59 (03), 220–226.

  • Google Scholar

• 94

  WangS.GuoZ.ZhouB.HeY.LiD.TaoP.et al (2024b). Research progress on safety and quality control of red yeast rice. Chin. Pharm. J.59 (13), 1186–1192.

  • Google Scholar

• 95

  WangT.LiJ. (2018). The treatment of hyperlipidemia with traditional Chinese medicine Fermentum Rubrum decoction and its effect on vascular endothelial protection. J. Liaoning Univ. Tradit. Chin. Med.20 (08), 119–121. 10.13194/j.issn.1673-842x.2018.08.031

  • CrossRef
  • Google Scholar

• 96

  WangW.WangJ.SuM.LuZ.KouW. (1995). Clinical observation of Xuezhikang capsules in the treatment of hyperlipidemia. Chin. J. Exp. Tradit. Med. Formulae. (01), 37–41.

  • Google Scholar

• 97

  WangX.GaoX.HuangT.LiC. (2007). The effect of Fermentum Rubrum compound preparation on blood lipid regulation function in rats. Shaanxi Med. J. (01), 35–37.

  • Google Scholar

• 98

  WangX.ZouD.LiH.LiD. (2022). The effect of Fermentum Rubrum on blood lipids and nutritional status of hemodialysis patients. Chin. J. Gerontol.42 (23). 10.3969/j.issn.1005-9202.2022.23.015

  • CrossRef
  • Google Scholar

• 99

  WangY. (2016). QuEChERS UPLC-MRM-IDA criteria EPI determination of lovastatin in Fermentum Rubrum. China Licens. Pharm.13 (10), 21–24+39.

  • Google Scholar

• 100

  WangY.GaoX. (2006). Research on the quality standards of Zhibituo capsule. Sichuan Med. J. (05), 451–452. 10.16252/j.cnki.issn1004-0501-2006.05.006

  • CrossRef
  • Google Scholar

• 101

  WangY.WeiW.LiC. (2002). The therapeutic effect of special Fermentum Rubrum on experimental fatty liver disease in quail. Chin. J. Clin. Pharmacol. Ther. (04), 293–295.

  • Google Scholar

• 102

  WangY.ZhaoZ.HuangF.RenJ. (2006a). Research on the anti-inflammatory mechanism of Fermentum Rubrum. Chin. Rem. Clin. (05), 350–352.

  • Google Scholar

• 103

  WangY.ZhaoZ.HuangF.RenJ. (2006b). Experimental study on the anti-inflammatory effect of Fermentum Rubrum. Chin. J. New Drugs. (02), 96–98.

  • Google Scholar

• 104

  WangY.ZhaoZ.WangL.HuangF. (2008). The anti-inflammatory effect and mechanism of Fermentum Rubrum on collagen induced arthritis rats. Chin. J. New Drugs. (14), 1217–1221.

  • Google Scholar

• 105

  WeiR.ZhangX.HuS.ZhangQ.ZhangW. (2023). Reconstructed herb —— Fermentum Rubrum. Jilin J. Tradit. Chin. Med.43 (02), 222–224. 10.13463/j.cnki.jlzyy.2023.02.025

  • CrossRef
  • Google Scholar

• 106

  WenJ.ChangP.GuX.JinZ. (2001). Research progress on physiological activity and determination methods of Fermentum Rubrum and Lovastatin. China Food Addit. (01), 12–19.

  • Google Scholar

• 107

  WenZ.ZhangF.HuangY.XieJ.LuoJ.WeiZ.et al (2011). Determination of Fermentum Rubrum content in Zhibitai capsules. China Pharm.20 (13), 21–23.

  • Google Scholar

• 108

  WuC.HuangJ.WangW.LuJ. (2007a). Bone tissue morphometric observation of Fermentum Rubrumt promoting fracture healing in experimental rats. J. Zhejiang Univ. Tradit. Chin. Med. (01), 41–43. 10.16466/j.issn1005-5509.2007.01.015

  • CrossRef
  • Google Scholar

• 109

  WuC.HuangJ.WangW.LuJ. (2007b). Experimental study on the treatment of experimental rat fractures with Fermentum Rubrum. Fujian J. Tradit. Chin. Med. (01), 42–44.

  • Google Scholar

• 110

  WuC.LuJ.WangW.ChenB. (2006). The effect of Fermentum Rubrum on BMP-2 expression in cultured rat osteoblasts in vitro. J. Tradit. Chin. Orthop. Traumatol. (05), 5–6+79.

  • Google Scholar

• 111

  WuM.WangW.ZhangW.ZhengG.LiuL. (2005). Clinical study on the treatment of hyperlipidemia with lipid-lowering Fermentum Rubrum micro powder. J. Shandong Univ. Tradit. Chin. Med. (06), 433–435. 10.16294/j.cnki.1007-659x.2005.06.009

  • CrossRef
  • Google Scholar

• 112

  WuX.LuoD. (2013). Observation on the clinical effect of Fermentum Rubrum on carotid atherosclerotic plaque. Clin. J. Chin. Med.5 (22), 7–8.

  • Google Scholar

• 113

  XieJ.LiD.WangM.ChenZ.YuanW. (2010). Determination of Lovastatin content in Xuezhikang capsule by HPLC method. China Pharm. (Chongqing, China). 21 (45), 4287–4289.

  • Google Scholar

• 114

  XieZ. (1996). Further study on traditional Chinese medicine Fermentum Rubrum by modern technology. China Med. news.22, 13–14.

  • Google Scholar

• 115

  XuH.RuanJ.GaoF.LiM. (2019). Clinical study on the treatment of hyperlipidemia with Shateng Fermentum Rubrum soft capsules. Mod. Tradit. Chin. Med.39 (05), 61–64. 10.13424/j.cnki.mtcm.2019.05.019

  • CrossRef
  • Google Scholar

• 116

  XuS.ShaoY.WuT. (2018). Overview of research on anti-tumor active ingredients extracted from Fermentum Rubrum. Glob. Tradit. Chin. Med.11 (06), 973–978.

  • Google Scholar

• 117

  XuY.WeiL.HeD.WangM. (2000). Determination of phosphatidylcholine content in Fermentum Rubrum and its preparation Xuezhikang. China J. Chin. Mater. Med. (12), 16–17.

  • Google Scholar

• 118

  XuY.WeiL.HeD.WangM. (2001). Thin layer scanning method for determining the content of daidzein in Fermentum Rubrum and its preparation Xuezhikang. China J. Chin. Mater. Med.26 (1). 10.3321/j.issn:1001-5302.2001.01.010

  • CrossRef
  • Google Scholar

• 119

  YanS. (1999). Development of vinegar bean capsule and the effect of lowering blood lipid. Fujian J. Tradit. Chin. Med. (01), 39–40.

  • Google Scholar

• 120

  YangY.LiuJ.ZhangY.GuoZ.LuoY.ChenD.et al (2024). Observation of clinical efficacy and network pharmacological mechanism analysis of Coptis chinensis-Fermentum Rubrum drug in non-alcoholic fatty liver disease. J. Shaanxi Univ. Tradit. Chin. Med.47 (02), 76–82. 10.13424/j.cnki.jsctcm.2024.02.015

  • CrossRef
  • Google Scholar

• 121

  YinM.YeH.FengS.ZhangX. (2016). Retrospective analysis of Fermentum Rubrum compound preparation in the treatment of primary dyslipidemia of phlegm turbidity and blood stasis type. Mod. Clin. Tradit. Chin. Med.23 (04), 8–11.

  • Google Scholar

• 122

  YuL.XuJ.ZhengJ.LuB. (2023). Exploring the mechanism of action of Fermentum Rubrum hawthorn in treating NASH based on network pharmacology and verifying the mechanism of NF - κ B signaling pathway. J. Zhejiang Univ. Tradit. Chin. Med.47 (09), 986–1001. 10.16466/j.issn1005-5509.2023.09.003

  • CrossRef
  • Google Scholar

• 123

  YuY.QuX.LiZ.GuoZ. (2000). Yunnan Fermentum Rubrum powder modulates blood lipid and anti-atherosclerotic plaque formation. Chin. Pharmacol. Bull. (05), 587–588.

  • Google Scholar

• 124

  ZhaiP.ZhaoJ.ZhouD.HongX. (2012). Experimental study on the lipid-lowering effect of traditional Chinese medicine Fermentum Rubrum compound preparation. J. Zhejiang Univ. Tradit. Chin. Med.36 (01), 70–72. 10.16466/j.issn1005-5509.2012.01.032

  • CrossRef
  • Google Scholar

• 125

  ZhangJ.MengF.MiaoT.JiL.ZhangJ. (2017). Study on the effects of Fermentum Rubrum polysaccharides on several important physiological indicators in rats. Heilongjiang J. Anim. Sci. Vet. Med. (05), 203–205. 10.13881/j.cnki.hljxmsy.2017.0434

  • CrossRef
  • Google Scholar

• 126

  ZhangQ.WangJ.BaiG.WangH.CuiH. (2016). HPLC-DAD/FLD determination of the active ingredient Lovastatin and toxic ingredient kumquat in Fermentum Rubrum. Lishizhen Med. Mater. Med. Res.27 (04), 816–819.

  • Google Scholar

• 127

  ZhangQ.WeiQ.TangB.JinQ.LiuH. (2008). Determination of Lovastatin content in Fermentum Rubrum capsule by capillary electrophoresis. Chin. J. Exp. Tradit. Med. Formulae. (11), 4–6. 10.13422/j.cnki.syfjx.2008.11.005

  • CrossRef
  • Google Scholar

• 128

  ZhangS.MiW.ChenL. (2020). Observation on the therapeutic effect of traditional Chinese medicine Fermentum Rubrum on hyperlipidemia of different TCM constitution types. J. Pract. Tradit. Chin. Intern. Med.34 (08), 56–59. 10.13729/j.issn.1671-7813.Z20200152

  • CrossRef
  • Google Scholar

• 129

  ZhangW.HeW. (2016). Clinical observation on the treatment of 80 cases of simple hyperlipidemia with Fermentum Rubrum. Heilongjiang J. Tradit. Chin. Med.45 (06), 21–22.

  • Google Scholar

• 130

  ZhangX.ZhangY.LuoY. (2023). Study on the effect of Coptis chinensis-Fermentum Rubrum medicine on regulating the Nrf2/HO-1 pathway to improve non-alcoholic fatty liver disease. China J. Tradit. Chin. Med. Pharm. (2005-)39 (04), 19–24. 10.13412/j.cnki.zyyl.20230307.002

  • CrossRef
  • Google Scholar

• 131

  ZhangX.ZhouF.ShiJ. (1997). Determination of lovastatin content in Xuezhikang capsules and Fermentum Rubrum by high performance liquid chromatography. Chin. Med. News. (16), 23–24.

  • Google Scholar

• 132

  ZhangY.HouT.ZhangS. (2001). The Dtermination of lovastatin in red yeast rice by HPLC. Food Sci. (Beijing, China)22 (7). 10.3321/j.issn:1002-6630.2001.07.017

  • CrossRef
  • Google Scholar

• 133

  ZhangZ.LiuY.WuC. (2010). Determination of oleic acid and linoleic acid content in traditional Chinese medicine Fermentum Rubrum by GC method. Chin. J. Exp. Tradit. Med. Formulae.16 (02), 23–25. 10.13422/j.cnki.syfjx.2010.02.010

  • CrossRef
  • Google Scholar

• 134

  ZhaoJ.FeiY.ShaoY. (2018). The effect of traditional Chinese medicine Fermentum Rubrum on blood lipids and liver function in patients with hyperlipidemia and liver dysfunction. J. Med. Theor. Pract.31 (21), 3226–3228. 10.19381/j.issn.1001-7585.2018.21.031

  • CrossRef
  • Google Scholar

• 135

  ZhaoJ.LiuX. (2011). Study on the lipid-lowering effect of Fermentum Rubrum plant sterol ester compound preparation. Chin. Tradit. Herb. Drugs42 (11), 2296–2299.

  • Google Scholar

• 136

  ZhengJ.GuoJ.JinZ. (2007). Study on the hypotensive mechanism of Fermentum Rubrum on spontaneously hypertensive rats. Sci. Technol. Food Ind. (03), 207–208+236.

  • Google Scholar

• 137

  ZhengW.LinJ.LinF.WuL. (2022). Comparison of lipid-lowering efficacy of functional Monascus and lovastatin. China Brew.41 (4). 10.11882/j.issn.0254-5071.2022.04.019

  • CrossRef
  • Google Scholar

• 138

  ZhengY.LiY. (2015). Clinical study on the treatment of hyperlipidemia with Fermentum Rubrum extract preparation. Clin. J. Chin. Med.7 (09), 36–37.

  • Google Scholar

• 139

  ZhouD. (2014). The effect of traditional Chinese medicine Fermentum Rubrum on blood lipids in high-fat diet rats. China Mod. Med.21 (16), 19–21.

  • Google Scholar

• 140

  ZhouF.ZhuX.PanP.ChenY.ChengD. (2011). Study on the anti-tumor activity of extracellular polysaccharides from Monascus purpureus. Chin. Arch. Tradit. Chin. Med.29 (01), 123–124. 10.13193/j.archtcm.2011.01.125.zhoufm.063

  • CrossRef
  • Google Scholar

• 141

  ZhouX.WangM.LuoW.WangL.GaoF.WeiP. (2018). Experimental study on the lipid-lowering effect of Seabuckthorn Fermentum Rubrum capsules. Pharmacol. Clin. Chin. Mater. Med.34 (05), 116–118. 10.13412/j.cnki.zyyl.2018.05.028

  • CrossRef
  • Google Scholar

• 142

  ZhuQ. (2013). Observation of the clinical efficacy of Xuezhikang capsule in the treatment of 40 cases of unstable angina Pectoris. Everyone’s Health (Late Ed.)7 (2).

  • Google Scholar

• 143

  ZhuW.JingG.ZhaoR.BiT.ZhaoD.WangS.et al (2023). Simultaneous determination of 10 fungal toxins in Fermentum Rubrum by HPLC tandem mass spectrometry. China Pharm.32 (03), 89–93.

  • Google Scholar

• 144

  ZhuY.LinX.YanG. (2025). “Kobayashi Pharmaceutical's health product scandal shakes Japan,” in Global Times. p 004.

  • Google Scholar