Citrisorbicillinol, an undescribed hybrid sorbicillinoid with osteogenic activity from Penicillium citrinum ZY-2.

Citrisorbicillinol (1), along with six other known compounds (2-7), was isolated from an endphyte Penicillium citrinum ZY-2 of Plantago asiatica L. Citrisorbicillinol (1) was characterized as a skeletally unprecedented hybrid sorbicillinoid, and its unique framework is likely formed by intermolecular [4 + 2] cycloaddition between intermediates derived from citrinin and sorbicillinoid biosynthetic gene clusters. Compounds 1 and 2 demonstrated to promote osteoblastic differentiation in MC3T3-E1 cells, and to be osteogenic in the prednisolone induced osteoporotic zebrafish. Compounds 3-7 exhibited moderate cytotoxicity against four human cancer cell lines.

The marine Penicillium sp. GGF16-1-2 metabolite dicitrinone G inhibits pancreatic angiogenesis by regulating the activation of NLRP3 inflammasome.

Citrinin derivatives have been found to have various pharmacological activities, such as anti-inflammatory, anti-tumor, and antioxidant effects. Dicitrinone G (DG) was a new citrinin dimer isolated from marine-derived fungus Penicillium sp. GGF 16-1-2 which has potential activity. Here, we aim to investigate whether DG has anti-pancreatic cancer activity. In xenograft tumor model, 2 × 106 BXPC-3 cells were injected into the hind flank of NU/NU nude mice by subcutaneously for 2 weeks followed by treating with DG (0.25, 0.5, 1 mg/kg) and 5-FU (30 mg/kg) for 4 weeks. Tumor volume and weight were measured, and the expression of CD31, IL-18, NLRP3, and Caspase-1 in tumor tissue were detected. In vitro, HUVECs were treated with conditioned medium (CM) derived from BXPC-3 cells, the effects of DG on angiogenesis were detected by tube formation and western blot analysis. In vivo studies showed that the tumor growth and angiogenesis were greatly suppressed. The tumor weight inhibition rates of DG and 5-FU groups were about 42.36%, 38.94%, 43.80%, and 31.88%. Furthermore, the expression of CD31 and Caspase-1 were decreased. In vitro, CM derived from BXPC-3 cells which treated with DG could inhibit the tube formation and expression of pro-angiogenic NICD in HUVECs. Our study suggests that DG could suppress angiogenesis via the NLRP3/IL-18 pathway and may have the potential to inhibit tumor development.

Transportation of citrinin is regulated by the CtnC gene in the medicinal fungus Monascus purpureus. / 药用真菌紫色红曲霉通过CtnCåŸºå› è°ƒæŽ§æ¡”éœ‰ç´ çš„è½¬è¿.

Monascus is one of the most essential microbial resources in China, with thousands of years of history. Modern science has proved that Monascus can produce pigment, ergosterol, monacolin K, γ-aminobutyric acid, and other functionally active substances. Currently, Monascus is used to produce a variety of foods, health products, and pharmaceuticals, and its pigments are widely used as food additives. However, Monascus also makes a harmful polyketide component called citrinin in the fermentation process; citrinin has toxic effects on the kidneys such as teratogenicity, carcinogenicity, and mutagenicity (Gong et al., 2019). The presence of citrinin renders Monascus and its products potentially hazardous, which has led many countries to set limits and standards on citrinin content. For example, the citrinin limit is less than 0.04 mg/kg according to the Chinese document National Standard for Food Safety Food Additive Monascus (GB 1886.181-2016) (National Health and Family Planning Commission of the People's Republic of China, 2016), and the maximum level in food supplements based on rice fermented with Monascus purpureus is 100 µg/kg in the European Union (Commission of the European Union, 2019).

Peniciriols A and B, two new citrinin derivatives from an endophytic fungus Penicillum citrinum TJNZ-27.

Two undescribed citrinin derivatives, named peniciriols A-B (1-2), together with six known compounds were isolated from endophytic fungus Penicillum citrinum TJNZ-27. The structures of two new compounds were well established by the detail interpretation of NMR and HRESIMS data as well as ECD measurement powered by molecular calculation. Among them, compound 1 shared an unprecedented dimerized citrinin skeleton with the formation of an intriguing 9H-xanthene ring system, whereas compound 2 possess a highly substituted phenylacetic acid skeleton, which was rarely-occurring in natural secondary metabolites. Moreover, these novel compounds were tested for cytotoxic and antibacterial activities, whereas these novel compounds did not exhibit any noticeable cytotoxic or antibacterial activities.

Transportation of citrinin is regulated by the CtnC gene in the medicinal fungus Monascus purpureus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Monascus is one of the most essential microbial resources in China, with thousands of years of history. Modern science has proved that Monascus can produce pigment, ergosterol, monacolin K, γ-aminobutyric acid, and other functionally active substances. Currently, Monascus is used to produce a variety of foods, health products, and pharmaceuticals, and its pigments are widely used as food additives. However, Monascus also makes a harmful polyketide component called citrinin in the fermentation process; citrinin has toxic effects on the kidneys such as teratogenicity, carcinogenicity, and mutagenicity (Gong et al., 2019). The presence of citrinin renders Monascus and its products potentially hazardous, which has led many countries to set limits and standards on citrinin content. For example, the citrinin limit is less than 0.04 mg/kg according to the Chinese document National Standard for Food Safety Food Additive Monascus (GB 1886.181-2016) (National Health and Family Planning Commission of the People's Republic of China, 2016), and the maximum level in food supplements based on rice fermented with Monascus purpureus is 100 µg/kg in the European Union (Commission of the European Union, 2019).

Expression of citrinin biosynthesis gene in Liupao tea and effect of Penicillium citrinum on tea quality.

Similar to Pu-erh tea, Liupao tea is a post-fermented tea that is produced through natural fermentation by microorganisms. Penicillium citrinum is involved in multiple production processes of Liupao tea that can produce citrinin, a secondary metabolite with renal toxicity; however, the effect of P. citrinum on the quality of Liupao tea has not been investigated yet. Citrinin production is regulated by approximately 16 biosynthesis genes. However, little is known about the genetic background of citrinin in the complex Liupao tea system. In the present study, we cultured P. citrinum on potato dextrose agar and Liupao tea powder media and analyzed the changes of its nutritional components in Liupao tea. We selected six citrinin biosynthesis genes identified in Monascus exhibiting homology and high sequence similarity to those in P. citrinum and further analyzed the expression of citrinin biosynthesis genes in Liupao tea and the changes in citrinin yield. The results showed that the changes in nutritional components of Liupao tea were closely related to the growth and metabolism of P. citrinum and the quality of the tea. Decreases in the contents of soluble sugars (from 10.29% to 9.58%), soluble pectins (from 3.71% to 3.13%), free amino acids (from 3.84% to 3.14%), and tea polyphenols (from 22.84% to 18.78%) were noted. The Spearman's correlation analysis indicated that P. citrinum growth can improve the tea quality to some extent. Quantitative real-time PCR demonstrated that ctnA gene was a positive regulator of citrinin production regardless of the culture medium used. ctnA and orf5 expressions greatly influenced the metabolism of citrinin by P. citrinum in Liupao tea. In conclusion, the citrinin biosynthesis genes, ctnA and orf5, may be the promising targets for developing strategies to control P. citrinum infection and citrinin biosynthesis in Liupao tea.

Mass Spectrometry Metabolomics Approach Reveals Anti-Trichomonas vaginalis Scaffolds from Marine Fungi.

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) in the world caused by Trichomonas vaginalis. Failures in the treatment with the 5-nitroimidazole class including parasite resistance to metronidazole elicit new alternatives. Marine natural products are sources of several relevant molecules, presenting a variety of metabolites with numerous biological activities. In this work, we evaluated the anti-T. vaginalis activity of fungi associated with marine invertebrates by mass spectrometry-based metabolomics approaches. After screening of six marine fungi, extract from Penicillium citrinum FMPV 15 has shown to be 100% active against T. vaginalis, and the gel permeation column on Sephadex LH-20® yielded twelve organic fractions which five showed to be active. Metabolomics and statistical analyses were performed with all the samples (extract and fractions), and several compounds were suggested to be related to the activity. These components include citrinin, dicitrinin C, citreoisocoumarin, dihydrocitrinone, decarboxycitrinin, penicitrinone C, and others. The minimum inhibitory concentration (MIC) value of anti-T. vaginalis activity of citrinin was 200 µM. The marine fungi metabolites show potential as new alternatives to overcome drug resistance in T. vaginalis infections.

Development and evaluation of a qPCR detection method for citrinin in Liupao tea.

Penicillium is universal in dark tea, and Penicillium citrinum can produce a kidney toxin called citrinin (CIT). Determining CIT is difficult because of the complexity of the dark tea substrate and the diversity of CIT-producing fungi. Therefore, this study established a real-time PCR (qPCR) detection method for CIT-related synthetic genes (ctnD, orf1, ctnA, pksCT, orf5, orf7, and ctnG) in Liupao tea and determined the content of CIT in samples at different production stages and the toxin-producing abilities of fungi (Aspergillus oryzae, etc.) in Liupao tea. CIT was found in all samples during the pile-fermentation process of Liupao tea, and CIT was detected in two samples during the aging process. The established method demonstrated good sensitivity and specificity in detecting CIT-related synthetic genes. The reaction efficiency was within the preferred range of 100 ± 10%. CIT was not detected or was below the detection limit when the Ct value of one or more related synthetic genes was greater than 33.5. Therefore, the established qPCR method can effectively predict the production of CIT in Liupao tea, and it is applicable to the judgment of whether fungi produce CIT.

The role of ER stress and ATP/AMPK in oxidative stress meditated hepatotoxicity induced by citrinin.

Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological and ultrastructural results showed that citrinin-induced liver injury in Kunming mice, and the mechanism of citrinin-induced hepatotoxicity was studied in L02 cells. Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Secondly, citrinin inhibits proliferation and promotes apoptosis of L02 cells via disruption of mitochondria membrane potential, increase Bax/Bcl-2 ration, activation of caspase-3, 9, and enhance lactate dehydrogenase (LDH) release. Then, citrinin inhibits superoxide dismutase (SOD) activity and increases the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting oxidative damage in L02 cells; upregulates the protein expression of binding immunoglobulin protein (Bip), C/EBP homologous protein (CHOP), PKR-like ER kinase (PERK) and activating transcription factor6 (ATF6), inducing ER stress in L02 cells; increases the phosphorylation of AMP-activated protein kinase (AMPK) and decreases the content of adenosine-triphosphate (ATP), activating AMPK pathway in L02 cells. Eventually, pretreatment with NAC, an ROS inhibitor, alleviates citrinin-induced cell cycle G2/M arrest and apoptosis by inhibiting ROS-mediated ER stress; pretreatment with 4-PBA, an ER stress inhibitor, reversed ER stress and p-AMPK; pretreatment with dorsomorphin, an AMPK inhibitor, decreases citrinin-induced cell cycle G2/M arrest and apoptosis. In summary, citrinin induces cell cycle arrest and apoptosis to aggravate liver injury by activating ROS-ER stress-AMPK signaling pathway.

Powerful toxic activity of citrinin, a fungal phytotoxin, and its mode of action in onion cells.

The dose-related effects of citrinin (CTN) on various physiological, cytogenetic, biochemical, and anatomical parameters using Allium cepa L. bulbs as a test material were researched in the present study. The physiological parameters examinated were fresh weight, root length, root number, and germination percentage; the cytogenetic parameters were micronucleus (MN) frequency, chromosome aberration (CA), and mitotic index (MI); the biochemical parameters were catalase (CAT), superoxide dismutase (SOD) activities, malondialdehyde (MDA) level, and free proline contents. And the anatomical changes in root tip cells were investigated by cross-sections. For this aim, onion bulbs were splitted four groups as three applications and one control. The bulbs in the control group were treated with distilled water; the bulbs in the application groups were treated with 1 µM, 5 µM, and 10 µM doses of CTN for 7 days. CTN application caused a decrease in the physiological parameters compared to the control group. This treatment created an increase in the frequency of MN and CA, and a reduce in the MI. In addition, it induced a dose-dependent increase in CAT and SOD activities and MDA and proline contents compared to the control group. Moreover, after CTN application, anatomical changes such as flattened nucleus, cell wall thickening, and cell deformation were identified and it was found that these changes reached their maximum at 10 mg/L dose CTN. Concequently, CTN caused inhibitory effects and the Allium test material was found to be a useful bioindicator for monitoring these effects.

Cytogenotoxic evaluation of the acetonitrile extract, citrinin and dicitrinin-A from Penicillium citrinum.

Endophytic fungi are promising sources of bioactive substances; however, their secondary metabolites are toxic to plants, animals, and humans. This study aimed toevaluate the toxic, cytotoxic, mutagenic and oxidant/antioxidant activities of acetonitrile extract (AEPc), citrinin (CIT) and dicitrinin-A (DIC-A) of Penicillium citrinum. For this, the test substances at 0.5; 1.0; 1.5 and 2 µg/mLwere exposed for 24 and 48 h in Artemia salina, and 48 h in Allium cepa test systems. The oxidant/antioxidant test was evaluated in pre-, co- and post-treatment with the stressor hydrogen peroxide (H2O2) in Saccharomyces cerevisiae. The results suggest that the AEPc, CIT and DIC-A at 0.5; 1.0; 1.5 and 2 µg/mL showed toxicity in A. saline, with LC50 (24 h) of 2.03 µg/mL, 1.71 µg/mL and 2.29 µg/mL, and LC50 (48 h) of 0.51 µg/mL, 0.54 µg/mL and 0.54 µg/mL, respectively.In A. cepa, the test substances also exerted cytotoxic and mutagenic effects. The AEPc, CIT and DIC-A at lower concentrations modulated the damage induced by H2O2 in the proficient and mutant strains of S. cerevisiae for cytoplasmic and mitochondrial superoxide dismutase. Moreover, the AEPc at 2 µg/mL and CIT at the two highest concentrations did not affect the H2O2-induced DNA damage in the test strains. In conclusion, AEPc, CIT and DIC-A of P. citrinum may exert their toxic, cytotoxic and mutagenic effects in the test systems possibly through oxidative stress induction pathway.

Triton X-100 supplementation regulates growth and secondary metabolite biosynthesis during in-depth extractive fermentation of Monascus purpureus.

Extractive fermentation has been proven to be efficient in enhancing the secretion and production of secondary metabolites in submerged fermentation by Monascus spp., owing to increased cell membrane permeability and resolved product inhibition. In this study, we investigated the regulation effect of Triton X-100 on cell growth and secondary metabolite biosynthesis in submerged fermentation of M. purpureus DK. The results show that the maximum monascus pigments (MPs), citrinin (CIT) production, and specific growth rate are 136.86 U/mL, 4.57 mg/L, and 0.04 h-1, respectively, when 3 g/L of Triton X-100 is supplemented after fermentation for 10 d, and the extracellular MPs and CIT increased by 127.48% and 288.57%, respectively. RT-qPCR shows that the expression levels of MPs and CIT biosynthesis gene clusters are significantly upregulated, whereas those of glycolysis, tricarboxylic acid cycle, respiratory chains, and ATP synthase are downregulated. This study provides a vital strategy for extractive fermentation under extreme environmental conditions for further enhancing MP production.

Dietary Supplements Based on Red Yeast Rice-A Source of Citrinin?

Citrinin (CIT) is secondary metabolite of filamentous molds. This mycotoxin has nephrotoxic, hepatotoxic, embryocidal, and fetotoxic properties. It is also produced by several species of the three genera Penicillium spp., Aspergillus spp., and Monascus spp., which are used to make red yeast rice (RYR). The material for this study consisted of 15 dietary supplements containing an extract of fermented red rice, available on the Polish market. Samples were extracted using a MeOH-H2O mixture, cleaned-up with an immunoaffinity CitriTest HPLC column, and quantified by HPLC-FLD. None of the analyzed samples contained CIT above the established limit of detection (LOD). Studies on the presence of toxic metabolites in red yeast rice show the importance of regulating this product and of clear information on the label regarding the standardized amounts of monacolin.

Citrinin Determination in Food and Food Supplements by LC-MS/MS: Development and Use of Reference Materials in an International Collaborative Study.

The development of incurred reference materials containing citrinin (CIT) and their successful application in a method validation study (MVS) in order to harmonize CIT determination in food and food supplements are demonstrated. CIT-contaminated materials made of red yeast rice (RYR), wheat flour, and Ginkgo biloba leaves (GBL), as well as food supplements made of red yeast rice (FS-RYR) and Ginkgo biloba leaves (FS-GBL), were manufactured in-house via fungal cultivation on collected raw materials. The homogeneity and stability from randomly selected containers were verified according to the ISO 13528. CIT was found to be homogenously distributed and stable in all contaminated materials, with no significant degradation during the timescale of the MVS when storage was performed up to +4 °C. Next, an MVS was organized with eighteen international laboratories using the provided standard operating procedure and 12 test materials, including three RYRs (blank, <50 µg/kg, <2000 µg/kg), two wheat flours (blank, <50 µg/kg), two GBL powders (blank, <50 µg/kg), three FS-RYRs (blank, <50 µg/kg, <2000 µg/kg), and two FS-GBLs (blank, <50 µg/kg). The results of seven CIT-incurred materials showed acceptable within-laboratory precision (RSDr) varying from 6.4% to 14.6% and between-laboratory precision (RSDR) varying from 10.2% to 37.3%. Evidenced by HorRat values < 2.0, the results of the collaborative trial demonstrated that the applied analytical method could be standardized. Furthermore, the appropriateness of producing CIT reference materials is an important step towards food and feed quality control systems and the organization of proficiency tests.

Antioxidant and antifatigue effect of a standardized fraction (HemoHIM) from Angelica gigas, Cnidium officinale, and Paeonia lactiflora.

CONTEXT: HemoHIM is an herbal preparation containing Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) developed for immune regulation. To date, studies on the antifatigue effects of HemoHIM have not been conducted. OBJECTIVE: The antifatigue effects of HemoHIM using models of citrinin and exercise-induced chronic fatigue syndrome were investigated. MATERIALS AND METHODS: Citrinin-induced L6 skeletal muscle cells were treated with HemoHIM (125, 250, and 500 µg/mL). The antioxidant factors were analysed. ICR mice were divided into four groups (n = 10): control, HemoHIM 250, 500 mg/kg, and creatine 300 mg/kg, respectively. Mice were orally administered HemoHIM or creatine for three weeks; during this time, both rotarod test and forced swimming test (FST) were conducted. The latency time was investigated and antioxidant, antifatigue factors were analysed. RESULTS: HemoHIM significantly restored reduced antioxidant enzymes (SOD, CAT, Txn, GPx, GSr, and GCLC in HemoHIM 500 µg/mL) compared to the citrinin group in L6 cells. In vivo, HemoHIM significantly improved the latency time (FST; 279.88 ± 50.32 sec, rotarod test; 552.35 ± 23.50 sec in HemoHIM 500 mg/kg). Moreover, the FST-induced reduction in glucose and glutathione significantly increased by 3-fold (HemoHIM 500 mg/kg) and increase in LDH and MDA were significantly inhibited by 1.6, 2.1-fold in the HemoHIM 500 mg/kg compared to the control group.

Citrinin against breast cancer: A cytogenotoxicological study.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

Ochratoxin A and citrinin in green coffee and dietary supplements with green coffee extract.

The aim of this study was to determine the degree of mold contamination and mycotoxin levels in commercially available green coffee products and dietary supplements with green coffee extract. The study included 34 samples from green coffee products: raw beans (n = 16), ground coffee (n = 15) and instant coffee (n = 3), as well as 22 samples from dietary supplements in form of capsules (n = 19), tablets (n = 2) and sachets (n = 1). Total mold count was determined with spread-plate method. Anamorphic mold were identified based on their microscopic morphology and the type of sporulation. Concentrations of mycotoxins, ochratoxin A and citrinin, were quantified by means of HPLC-fluorescence detection. Molds, typically Aspergillus spp. and Penicillium spp., were found in 94% of green coffee beans, 100% of ground and instant coffee samples, and 55% of dietary supplement samples. None of the samples contained detectable levels of citrinin. Ochratoxin A (0.4 ng/g) was detected in only one sample of raw green coffee beans, but in up to 40% and 67% of ground and instant coffee samples, respectively. Mean concentrations of ochratoxin A in ground and instant coffee samples were 3.28 ng/g and 4.09 ng/g, respectively, and maximum concentrations amounted to 6.65 ng/g and 7.44 ng/g, respectively. Ochratoxin A (mean concentration 9.60 ng/g, maximum level 31.4 ng/g) was also detected in up to 58% of the supplement capsules, but in none of tablets and sachets.

Evaluation of Mycoflora and Citrinin Occurrence in Chinese Liupao Tea.

Citrinin (CIT), a known nephrotoxic mycotoxin, is mainly produced by Penicillium, Aspergillus, and Monascus species. It is a natural contaminant in cereal grains, foods, and feedstuff. Liupao tea (or Liubao tea) is a typical Chinese dark tea obtained via indigenous tea fermentation facilitated by microorganisms. Certain fungi present in Liupao tea that may produce CIT are a potential threat to consumer health. In the present study, various potential toxigenic mycoflora and the natural occurrence of CIT in Liupao tea were surveyed via the culture-dependent method, high performance liquid chromatography-fluorescence detection (HPLC-FLD), and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Total mold counts ranged from 3.5 × 102 CFU/g to 2.1 × 106 CFU/g tea in 28 tea samples. A total of 218 fungal isolates belonging to five genera and 23 species were identified. Some of these strains, such as Aspergillus ochraceus, Aspergillus oryzae, Penicillium citrinum, and Penicillium chrysogenum, may potentially be a CIT-producing species. In addition, 32.7% of 113 Liupao tea samples were contaminated with CIT at concentrations ranging from 7.8 to 206.1 µg/kg. These CIT concentrations in Liupao tea are chiefly attributed to climatic conditions and water activity during storage that favor fungal proliferation and mycotoxin production. However, CIT could not be detected in Liupao tea stored for over 10 years. These results provide the first information about the potential toxigenic mycoflora and natural occurrence of CIT in Liupao tea. Therefore, storage conditions and fungal community must be monitored to ensure the quality of Liupao tea.

Penctrimertone, a bioactive citrinin dimer from the endophytic fungus Penicillium sp. T2-11.

Penctrimertone (1), a novel citrinin dimer bearing a 6/6/6/6 tetracyclic ring scaffold, along with two known compounds xerucitrinic acid A (2) and citrinin (3) were isolated from the endophytic fungus Penicillium sp. T2-11. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1 was defined by a combination of TDDFT-ECD calculations and the DP4+ probability analysis based on NMR chemical shift calculations. Bioassays revealed that compound 1 exhibited noticeable antimicrobial activities and moderate cytotoxicity. A plausible biosynthetic pathway of 1 was also proposed.

Protective effect and mechanism of Monascus-fermented red yeast rice against colitis caused by Salmonella enterica serotype Typhimurium ATCC 14028.

Red yeast rice (RYR), a traditional Chinese fermented food, has the effect of lowering blood lipid and cholesterol, but little information is available about whether RYR can inhibit pathogenic bacterial infection in vivo. The present study explored the effect of RYR on Salmonella enterica-induced intestinal inflammation and gut microbiota dysbiosis in mice as well as the underlying anti-inflammatory mechanism. Results showed that RYR can alleviate S. enterica infection in vivo and Monascus pigments are the main functional components. The analysis of microbiota, gene expression profile and serological immunology revealed that RYR can regulate the intestinal flora and increase the relative abundance of beneficial bacteria such as Lactobacillus and Akkermansia. Meanwhile, RYR is also found to regulate the expression of pro-inflammatory factors and tight junction-related genes to inhibit the NO and NF-κB-mediated inflammatory response and maintain the integrity of the intestinal barrier. This study provides a new dietary intervention strategy for the prevention of pathogenic bacterial infection.