Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation.

Background: Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis. Methods: We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism. Results: In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3. Conclusion: This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.

The impact of a modified microbiota-accessible carbohydrate diet on gut microbiome and clinical symptoms in colorectal cancer patients following surgical resection.

A high-fiber diet is widely recognized for its positive effects on the gut microbiome. However, the specific impact of a high-fiber diet on the gut microbiome and bowel habits of patients with colon cancer remains poorly understood. In this study, we aimed to assess the effects of a modified microbiota-accessible carbohydrate (mMAC) diet on gut microbiota composition and clinical symptoms in colon cancer patients who underwent surgical resection. To achieve this, we enrolled 40 patients in two groups: those who received adjuvant chemotherapy and those who did not. Fecal samples were collected before and after dietary interventions for microbial and metabolite analyses. Each group was randomized in a 1: 1 ratio to follow either a 3-week conventional diet followed by a 3-week mMAC diet, or the reverse sequence. Although there were no significant differences in the microbial diversity data before and after the mMAC diet in both the non-chemotherapy and chemotherapy groups, distinct differences in gut microbial composition were revealed after the mMAC diet. Specifically, the abundance of Prevotella, which is associated with high-fiber diets, was further elevated with increased concentrations of acetate and propionate after the mMAC diet. Additionally, patients who experienced improved diarrhea and constipation after the mMAC diet exhibited an enrichment of beneficial bacteria and notable changes in metabolites. In conclusion, this study provides valuable insights into the potential benefits of the mMAC diet, specifically its impact on the gut microbiome and clinical symptoms in postoperative colorectal cancer (CRC) patients. These findings emphasize the potential role of a high-fiber diet in influencing the gut microbiome, and the clinical symptoms warrant further investigation.

Antimicrobial properties of Pediococcus acidilactici and Pediococcus pentosaceus isolated from silage.

AIMS: The objective of this study was to isolate multifunctional bacteriocin-producing strains; to characterize the expressed bacteriocin for the control of Listeria monocytogenes and vancomycin-resistant Enterococcus; to evaluate the safety of studied strains; and to explore their antifungal activity. METHODS AND RESULTS: Two Pediococcus strains were isolated from silage samples obtained from an organic farm in Belogradchik, Bulgaria. The strains were identified by 16S rRNA sequencing analysis and characterized as bacteriocins producers. Strong antimicrobial activity was detected against more than 74 different strains of Listeria monocytogenes, 27 different vancomycin-resistant Enterococcus strains. In addition, studied strains were able to inhibit the growth of strains of Alternaria alternate, Aspergillus flavus, Aspergillus niger, Cladosporium sphaerospermum, Penicillium chrysogenum and Penicillium expansum. Some aspects of the antimicrobial mode of action were evaluated, including killing curves and aggregation properties. Both strains generated positive PCR results for the presence of pediocin PA-1, but not for other bacteriocins evaluated in this screening process. Metabolomic analysis of the cell-free supernatants from both strains was performed in order to explain the observed antifungal activity against different moulds. According to PCA and PLS-DA score plot, P. acidilactici ST3522BG and P. pentosaceus ST3633BG were clearly clustered from control (MRS). Increases in the production of benzoic acid, 2-hydroxyisocaproic acid, ß-phenyl-lactic acid, α-hydroxybutyric acid and 1,3-butanediol were recorded, these metabolites were previously described as antifungal. CONCLUSIONS: Pediococcus acidilactici ST3522BG and P. pentosaceus ST3633BG were evaluated as producing bacteriocin strains with high specificity against Listeria and vancomycin-resistant Enterococcus species. In addition, both investigated Pediococcus strains were evaluated as producer of effective antifungal metabolites with potential for the inhibition of mycotoxin-producing moulds. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this report is a pioneer in the evaluation of Pediococcus strains isolated from silage with highly specific bacteriocinogenic antimicrobial activity against Listeria spp. and vancomycin-resistant Enterococcus spp., and antifungal activity against mycotoxin-producing moulds.

Characterization and safety evaluation of two beneficial, enterocin-producing Enterococcus faecium strains isolated from kimchi, a Korean fermented cabbage.

Enterococcus faecium ST20Kc and ST41Kc were isolated from kimchi, a traditional Korean fermented cabbage. Bacteriocins produced by both strains exhibited strong activity against Listeria monocytogenes and various Enterococcus spp., including 30 vancomycin-resistant enterococcal strains, but not against other lactic acid bacteria (LAB) on the evaluated test panel. The antimicrobials produced by the strains were found to be proteinaceous and stable even after exposure to varying pH, temperature, and chemicals used in the industry and laboratory processes. Antimicrobial activity of both strains was evaluated as bactericidal against exponentially growing cultures of L. monocytogenes ATCC® 15313™ and Enterococcus faecalis 200A. Based on tricine-SDS-PAGE, the molecular weights of the bacteriocins produced by the strains were between 4 and 6 kDa. Additionally, both strains were susceptible to antibiotics, including vancomycin, kanamycin, gentamycin, ampicillin, streptomycin, tylosin, chloramphenicol, clindamycin, and tetracycline. Adhesion genes, map, mub, and EF-Tu, were also detected in the genomes of both strains. With gastrointestinal stress induction, both strains showed high individual survival rates, and capability to reduce viable counts of L. monocytogenes ATCC® 15313™ and Enterococcus faecalis 200A in mixed cultures. Based on the metabolomics analysis, both strains were found to produce additional antimicrobial compounds, particularly, lactic acid, phenyllactic acid, and phenethylamine, which can be potentially involved in the antimicrobial interaction with pathogenic microorganisms.

Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

Assessment of the safety and anti-inflammatory effects of three Bacillus strains in the respiratory tract.

Chronic respiratory diseases are part of accumulating health problems partly due to worldwide increase in air pollution. By their antimicrobial and immunomodulatory properties, some probiotics constitute promising alternatives for the prevention and treatment of chronic respiratory diseases. We have isolated Bacillus strains from Korean fermented foods and selected three potentially probiotic strains (two Bacillus subtilis and one Bacillus amyloliquefaciens) based on safety, antimicrobial efficacy, activity against airborne pathogens and their immunomodulatory properties in vivo. Safety evaluation included in silico analysis for confirming absence of virulence genes. Safety for the respiratory tract was confirmed by an in vivo pathogenicity test using a murine model. Antimicrobial activity was displayed against several airborne pathogens. Potential antimicrobial metabolites such as 2,3-butanediol and propylene glycol were identified as possible antagonistic agents. Immunomodulatory properties in vitro were confirmed by upregulation of IL-10 expression in a macrophage cell line. Intranasal instillation and inhalation in an ovalbumin (OVA)-induced lung inflammation murine model reduced T helper type 2 (Th2) cytokines at transcriptional and protein levels in the lungs. The safety and potentially beneficial role of these Bacillus strains could be demonstrated for the respiratory tract of a murine model.

Elucidating the involvement of apoptosis in postmortem proteolysis in porcine muscles from two production cycles using metabolomics approach.

Apoptosis has been suggested as the first step in the process of conversion of muscle into meat. While a potential role of apoptosis in postmortem proteolysis has been proposed, the underlying mechanisms by which metabolome changes in muscles would influence apoptotic and proteolytic process, leading to meat quality variation, has not been determined. Here, apoptotic and proteolytic attributes and metabolomics profiling of longissimus dorsi (LD) and psoas major (PM) muscles in pigs from two different production cycles (July-Jan vs. Apr-Sep) were evaluated. PM showed higher mitochondrial membrane permeability (MMP), concurrent with less extent of calpain-1 autolysis and troponin T degradation and higher abundance of HSP27 and αß-crystallin compared to LD (P < 0.05). Apr-Sep muscles showed concurrence of extended apoptosis (indicated by higher MMP), calpain-1 autolysis and troponin T degradation, regardless of muscle effects (P < 0.05). Metabolomics profiling showed Apr-Sep muscles to increase in oxidative stress-related macronutrients, including 6-carbon sugars, some branched-chain AA, and free fatty acids. Antioxidant AA (His and Asp) and ascorbic acid were higher in July-Jan (P < 0.05). The results of the present study suggest that early postmortem apoptosis might be positively associated with pro-oxidant macronutrients and negatively associated with antioxidant metabolites, consequently affecting meat quality attributes in a muscle-specific manner.

Characterization of Metabolic Changes under Low Mineral Supply (N, K, or Mg) and Supplemental LED Lighting (Red, Blue, or Red-Blue Combination) in Perilla frutescens Using a Metabolomics Approach.

In order to achieve premium quality with crop production, techniques involving the adjustment of nutrient supply and/or supplemental lighting with specific light quality have been applied. To examine the effects of low mineral supply and supplemental lighting, we performed non-targeted metabolite profiling of leaves and stems of the medicinal herb Perilla frutescens, grown under a lower (0.75×) and lowest (0.1×) supply of different minerals (N, K, or Mg) and under supplemental light-emitting diode (LED) lighting (red, blue, or red-blue combination). The lowest N supply increased flavonoids, and the lowest K or Mg slightly increased rosmarinic acid and some flavonoids in the leaves and stems. Supplemental LED lighting conditions (red, blue, or red-blue combination) significantly increased the contents of chlorophyll, most cinnamic acid derivatives, and rosmarinic acid in the leaves. LED lighting with either blue or the red-blue combination increased antioxidant activity compared with the control group without LED supplementation. The present study demonstrates that the cultivation of P. frutescens under low mineral supply and supplemental LED lighting conditions affected metabolic compositions, and we carefully suggest that an adjustment of minerals and light sources could be applied to enhance the levels of targeted metabolites in perilla.

Heat-responsive and time-resolved transcriptome and metabolome analyses of Escherichia coli uncover thermo-tolerant mechanisms.

Current understanding of heat shock response has been complicated by the fact that heat stress is inevitably accompanied by changes in specific growth rates and growth stages. In this study, a chemostat culture was successfully performed to avoid the physico-chemical and biological changes that accompany heatshock, which provided a unique opportunity to investigate the full range of cellular responses to thermal stress, ranging from temporary adjustment to phenotypic adaptation at multi-omics levels. Heat-responsive and time-resolved changes in the transcriptome and metabolome of a widely used E. coli strain BL21(DE3) were explored in which the temperature was upshifted from 37 to 42 °C. Omics profiles were categorized into early (2 and 10 min), middle (0.5, 1, and 2 h), and late (4, 8, and 40 h) stages of heat stress, each of which reflected the initiation, adaptation, and phenotypic plasticity steps of the stress response. The continued heat stress modulated global gene expression by controlling the expression levels of sigma factors in different time frames, including unexpected downregulation of the second heatshock sigma factor gene (rpoE) upon the heat stress. Trehalose, cadaverine, and enterobactin showed increased production to deal with the heat-induced oxidative stress. Genes highly expressed at the late stage were experimentally validated to provide thermotolerance. Intriguingly, a cryptic capsular gene cluster showed considerably high expression level only at the late stage, and its expression was essential for cell growth at high temperature. Granule-forming and elongated cells were observed at the late stage, which was morphological plasticity occurred as a result of acclimation to the continued heat stress. Whole process of thermal adaptation along with the genetic and metabolic changes at fine temporal resolution will contribute to far-reaching comprehension of the heat shock response. Further, the identified thermotolerant genes will be useful to rationally engineer thermotolerant microorganisms.

Metabolomic response of Perilla frutescens leaves, an edible-medicinal herb, to acclimatize magnesium oversupply.

High salt accumulation, resulting from the rampant use of chemical fertilizers in greenhouse cultivation, has deleterious effects on plant growth and crop yield. Herein, we delineated the effects of magnesium (Mg) oversupply on Perilla frutescens leaves, a traditional edible and medicinal herb used in East-Asian countries. Mg oversupply resulted in significantly higher chlorophyll content coupled with lower antioxidant activities and growth, suggesting a direct effect on subtle metabolomes. The relative abundance of bioactive phytochemicals, such as triterpenoids, flavonoids, and cinnamic acids, was lower in the Mg-oversupplied plants than in the control. Correlation analysis between plant phenotypes (plant height, total fresh weight of the shoot, leaf chlorophyll content, and leaf antioxidant content) and the altered metabolomes in P. frutescens leaves suggested an acclimatization mechanism to Mg oversupply. In conclusion, P. frutescens preferentially accumulated compatible solutes, i.e., carbohydrates and amino acids, to cope with higher environmental Mg levels, instead of employing secondary and antioxidative metabolism.

Multivitamin and Mineral Supplementation Containing Phytonutrients Scavenges Reactive Oxygen Species in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Phytonutrients and vitamin and mineral supplementation have been reported to provide increased antioxidant capacity in humans; however, there is still controversy. In the current clinical trial, we examined the antioxidant and DNA protection capacity of a plant-based, multi-vitamin/mineral, and phytonutrient (PMP) supplementation in healthy adults who were habitually low in the consumption of fruits and vegetables. This study was an eight-week, double-blind, randomized, parallel-arm, and placebo-controlled trial. PMP supplementation for eight weeks reduced reactive oxygen species (ROS) and prevented DNA damage without altering endogenous antioxidant system. Plasma vitamins and phytonutrients were significantly correlated with ROS scavenging and DNA damage. In addition, gene expression analysis in PBMC showed subtle changes in superoxide metabolic processes. In this study, we showed that supplementation with a PMP significantly improved ROS scavenging activity and prevented DNA damage. However, additional research is still needed to further identify mechanisms of actions and the role of circulating phytonutrient metabolites.

Therapeutic Effect of Ecklonia cava Extract in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy. Ecklonia cava (E. cava) is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects of E. cava extract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to the E. cava extract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the E. cava-treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels, Ar, and Esr2 levels were markedly increased in the E. cava-treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that the E. cava extract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.

Distinguishing Six Edible Berries Based on Metabolic Pathway and Bioactivity Correlations by Non-targeted Metabolite Profiling.

Berries have been used as valuable sources of polyphenols for human health; however, injudicious uses of berries are widespread without regard to the specific metabolite constituent of each berry. We classified 6 different edible berries (honeyberry, blueberry, mandarin melonberry, mulberry, chokeberry, and Korean black raspberry) based on their metabolite distributions in biosynthetic pathways by non-targeted metabolite profiling and bioactive correlation analysis. Principal component analysis revealed a distinct clustering pattern of metabolites for each berry. Metabolic pathway analysis revealed different biosynthetic routes of secondary metabolites in each berry. Mandarin melonberry contains a relatively higher proportion of genistein, genistein glycoside, and genistein-derived isoflavonoids and prenylflavonoids than the other berries. Various anthocyanin glycosides, synthesized from dihydroquercetin and cyanidin, were more abundant in chokeberry and honeyberry, whereas high levels of flavonoid-and anthocyanins-rutinoside forms were observed in Korean black raspberry. The levels of anthocyanins derived from dihydromyricetin were high in blueberry. The highest anti-oxidant activity was observed in chokeberry and Korean black raspberry, which is positively related to the proportional concentration of flavonoids, phenolics, and anthocyanins. The lowest sugar contents were observed in Korean black raspberry, highest acidity in honeyberry, and lowest acidity in mandarin melonberry, which were specific characteristics among the berries. Taken together, biosynthetic pathway and physicochemical characteristics analyses revealed that the different synthesized routes of flavonoids and anthocyanins and associated bio-activities may be distinct features in each berry and explain their phenotypic diversity at the molecular level.

Metabolomic and lipidomic analysis of the effect of pioglitazone on hepatic steatosis in a rat model of obese Type 2 diabetes.

BACKGROUND AND PURPOSE: Thiazolidinediones, acting as PPAR-γ ligands, reduce hepatic steatosis in humans and animals. However, the underlying mechanism of this action remains unclear. The purpose of this study was to investigate changes in hepatic metabolites and lipids in response to treatment with the thiazolidinedione pioglitazone in an animal model of obese Type 2 diabetes. EXPERIMENTAL APPROACH: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were orally administered either vehicle (control) or pioglitazone (30 mg·kg-1 ) and fed a high-fat diet (60% kcal fat) for 12 weeks. Hepatic metabolites were analysed via metabolomic and lipidomic analyses. Gene expression and PLA2 activity were analysed in livers from pioglitazone-treated and control rats. KEY RESULTS: OLETF rats that received pioglitazone showed decreased fat accumulation and improvement of lipid profiles in the liver compared to control rats. Pioglitazone treatment significantly altered levels of hepatic metabolites, including free fatty acids, lysophosphatidylcholines and phosphatidylcholines, in the liver. In addition, pioglitazone significantly reduced the expression of genes involved in hepatic de novo lipogenesis and fatty acid uptake and transport, whereas genes related to fatty acid oxidation were up-regulated. Gene expression and enzyme activity of PLA2 , which hydrolyzes phosphatidylcholines to release lysophosphatidylcholines and free fatty acids, were significantly decreased in the livers of pioglitazone-treated rats compared to control rats. CONCLUSIONS AND IMPLICATIONS: Our results present evidence for the ameliorative effect of pioglitazone on hepatic steatosis, largely due to the regulation of lipid metabolism, including fatty acids, lysophosphatidylcholines, phosphatidylcholines and related gene-expression patterns.

Systematic metabolic profiling and bioactivity assays for bioconversion of Aceraceae family.

Plants are an important and inexhaustible source of bioactive molecules in food, medicine, agriculture, and industry. In this study, we performed systematic liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling coupled with antioxidant assays for indigenous plant family extracts. Partial least-squares discriminant analysis of LC-MS datasets for the extracts of 34 plant species belonging to the families Aceraceae, Asteraceae, and Rosaceae showed that these species were clustered according to their respective phylogenies. In particular, seven Aceraceae species were clearly demarcated with higher average antioxidant activities, rationalizing their application for bioconversion studies. On the basis of further evaluation of the interspecies variability of metabolic profiles and antioxidant activities among Aceraceae family plants, we found that Acer tataricum (TA) extracts were clearly distinguished from those of other species, with a higher relative abundance of tannin derivatives. Further, we detected a strong positive correlation between most tannin derivatives and the observed higher antioxidant activities. Following Aspergillus oryzae-mediated fermentative bioconversion of Acer plant extracts, we observed a time-correlated (0-8 days) linear increase in antioxidant phenotypes for all species, with TA having the highest activity. Temporal analysis of the MS data revealed tannin bioconversion mechanisms with a relatively higher abundance of gallic acid (m/z 169) accumulated at the end of 8 days, particularly in TA. Similarly, quercetin precursor (glycoside) metabolites were also transformed to quercetin aglycones (m/z 301) in most Acer plant extracts. The present study underscores the efficacy of fermentative bioconversion strategies aimed at enhancing the quality and availability of bioactive metabolites from plant extracts.

Unraveling Metabolic Variation for Blueberry and Chokeberry Cultivars Harvested from Different Geo-Climatic Regions in Korea.

Temporal geo-climatic variations are presumably vital determinants of phenotypic traits and quality characteristics of berries manifested through reconfigured metabolomes. We performed an untargeted mass spectrometry (MS)-based metabolomic analysis of blueberry (Vaccinium spp.) and chokeberry (Aronia melanocarpa) sample extracts harvested from different geo-climatic regions in Korea. The multivariate statistical analysis indicated distinct metabolite compositions of berry groups based on different species and regions. The amino acids levels were relatively more abundant in chokeberry than in blueberry, while the sugar contents were comparatively higher in blueberry. However, the metabolite compositions were also dependent on geo-climatic conditions, especially latitude. Notwithstanding the cultivar types, amino acids, and sucrose were relatively more abundant in berries harvested from 35°N and 36°N geo-climatic regions, respectively, characterized by distinct duration of sunshine and rainfall patterns. The present study showed the ability of a metabolomics approach for recapitulating the significance of geo-climatic parameters for quality characterization of commercial berry types.

In vivo metabolomic interpretation of the anti-obesity effects of hyacinth bean (Dolichos lablab L.) administration in high-fat diet mice.

SCOPE: The esoteric anti-obesity effects of hyacinth bean (Dolichos lablab L) have largely remained unexplored. Herein, we investigated the anti-obesity mechanisms of hyacinth bean compared to milk thistle, a natural herb employed for ameliorating obesity-related diseases, using high-fat diet (HFD) fed mice towards unfolding the perplexing mechanisms. METHODS AND RESULTS: C57BL/6J mice were orally administered hyacinth bean (25 mg/kg/day) and milk thistle (100 mg/kg/day) for 9 weeks along with HFD. Intriguingly, a number of anti-obesity mechanisms indexed through clinical parameters, suppression in weight gains and liver steatosis were found similar to some disparity. Furthermore, the corresponding metabolic implications were studied through MS-based metabolite profiling, and using the Kyoto Encyclopedia of Genes and Genomes for metabolic pathways revealing that hyacinth bean or milk thistle administration effectively attenuates the HFD-induced lipid, glucose, and bile acid metabolism, with former specifically attenuates pyruvate-derived amino acids metabolism. Among them, valine, asparagine, and lysine displayed high correlation with blood clinical parameters. CONCLUSION: A lower dose of hyacinth bean resulted in similar anti-obesity effects as milk thistle, as confirmed by both clinical and metabolomics analyses. Equivocally, we conjecture that hyacinth bean could be used as a potent anti-obesity herbal functional food.

Metabolomics Provides Quality Characterization of Commercial Gochujang (Fermented Pepper Paste).

To identify the major factors contributing to the quality of commercial gochujang (fermented red pepper paste), metabolites were profiled by mass spectrometry. In principal component analysis, cereal type (wheat, brown rice, and white rice) and species of hot pepper (Capsicum annuum, C. annuum cv. Chung-yang, and C. frutescens) affected clustering patterns. Relative amino acid and citric acid levels were significantly higher in wheat gochujang than in rice gochujang. Sucrose, linoleic acid, oleic acid, and lysophospholipid levels were high in brown-rice gochujang, whereas glucose, maltose, and γ-aminobutyric acid levels were high in white-rice gochujang. The relative capsaicinoid and luteolin derivative contents in gochujang were affected by the hot pepper species used. Gochujang containing C. annuum cv. Chung-yang and C. frutescens showed high capsaicinoid levels. The luteolin derivative level was high in gochujang containing C. frutescens. These metabolite variations in commercial gochujang may be related to different physicochemical phenotypes and antioxidant activity.

Comparison of Metabolites Variation and Antiobesity Effects of Fermented versus Nonfermented Mixtures of Cudrania tricuspidata, Lonicera caerulea, and Soybean According to Fermentation In Vitro and In Vivo.

We used ultra-performance-liquid-chromatography with quadrupole-time-of-flight mass spectrometry to study the changes in metabolites in the mixture of Cudrania tricuspidata, Lonicera caerulea, and soybean (CLM) during fermentation. Additionally, the antiobesity effects of CLM and fermented-CLM (FCLM) were studied based on the analysis of plasma from high-fat diet (HFD)-fed mice. The levels of cyanidin and the glycosides of luteolin, quercetin, and cyanidin derived from L. caerulea were decreased, whereas the levels of luteolin and quercetin were increased during fermentation. Isoflavone glycosides and soyasaponins originating from the soybean were decreased, whereas their aglycones such as daidzein, glycitein, and genistein were increased. As for prenylated flavonoids from C. tricuspidata, these metabolites were decreased at the early stage of fermentation, and were increased at end of the fermentation. In terms of the functional food product, various metabolites derived from diverse natural products in CLM had complementary effects and demonstrated higher antioxidant and pancreatic lipase inhibition activities after fermentation; these activities were closely related to flavonoid aglycones including genistein, daidzein, glycitein, luteolin, and quercetin. In an in vivo experiment, several clinical parameters affected by HFD were improved by the administration of either CLM or FCLM, but there was a difference in the antiobesity effects. The levels of lysoPCs with C20:4, C16:0, and C22:6 were significantly attenuated by CLM administration, while the attenuated levels of lysoPCs with C20:4 and C18:2 were significantly restored by FCLM administration. These metabolites may explain the above-mentioned differences in antiobesity effects. Although only the changes in plasma lysophospholipids could not fully explain antiobesity effects between non-fermented and fermented plant mixtures from our results, we suggest that metabolomics approach could provide a way to reveal the metabolite alterations in the complex fermentation process and understand the differences or changes in bioactivity according to fermentation.

Metabolomics of Lonicera caerulea fruit during ripening and its relationship with color and antioxidant activity.

We performed mass spectrometry-based metabolites profiling in Lonicera caerulea fruits according to seven ripening stages. During ripening, fruit color significantly changed from green to red, with sugars, organic acids, phenolic acids, anthocyanins, and flavonoids significantly altered. In particular, the contents of cyanidin-3-glucoside, peonidin-glucoside, peonidin-3-rutinoside and cyanidin-3-rutinoside, which are closely associated with color, were elevated from stages four to seven. The changes of antioxidant activity during ripening were similar to those of total phenolic and flavonoid contents. L. caerulea fruits at stage six (pale-purple) had higher antioxidant activity and total phenolic and flavonoid contents with higher cyanidin-3,5-diglucoside contents than those at stage seven (fully purple). From this study, we revealed the changes in the contents of primary and secondary metabolites with antioxidant properties during ripening, and these results could be helpful to determine the optimal harvest stage of L. caerulea fruit.