This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/metabolism* ; Water ; Chromatography, Liquid ; Tryptophan ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Diarrhea/drug therapy* ; Biomarkers ; Riboflavin

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). Flavoproteins are involved in a wide array of biological processes, such as photosynthesis, DNA repair and natural product biosynthesis. It should be noted that 5%-10% of flavoproteins have a covalently linked flavin prosthetic group. Such covalent linkages benefit the holoenzyme in several ways including improving the stability and catalytic potency. During the past decade, significant progress has been made in covalent flavoproteins, especially with respect to enzyme-dependent biogenesis and discovery of novel linkage types. The present review gives a condensed overview of investigations published from March 2009 to December 2021, with emphasis on the discovery, biogenesis and their catalytic role in natural product biosynthesis.
Flavoproteins/metabolism* ; Flavin-Adenine Dinucleotide/metabolism* ; Flavin Mononucleotide/metabolism* ; Riboflavin ; Biological Products

OBJECTIVES: The purpose of this study was to assess energy and nutritional intake and investigate the preference for food and cooking methods of the residents in elderly care facilities. METHODS: Data were collected from 72 residents (10 males and 62 females) aged ≥ 70 years in elderly care facilities using questionnaires, food photographs for estimating dietary intake and records for daily physical activity. RESULTS: Average age of the study participants was 85.0 years and 41, 36 and 8 had dementia, hypertension and diabetes mellitus, respectively. 15%, 65% and 19% of subjects were physically mobile, enervated, and immobile, respectively. Daily energy intake was 1360.2 kcal in men and 1378.0 kcal in women, which were 68.0% and 86.1% of the estimated energy requirement (EER) of dietary reference intake for Koreans (KDRI) for ≥ 75 year old individuals, respectively. Estimated energy expenditure (EEE) of subjects calculated using formula from KDRI was 1361.9 kcal and EER calculated using estimated daily physical activity (EDPA) was 1232.9 kcal. Energy intake and EEE from KDRI were higher than EER from EDPA. Dietary intake of dietary fiber, calcium, potassium, zinc, vitamin B2, niacin, vitamin C were lower, and protein, phosphorous, iron, sodium, vitamin A, vitamin B1, vitamin B6, vitamin E were higher than the corresponding ones of KDRI. Subjects liked meats, fishes and shellfish, and fruits, while subjects disliked milk, seaweeds and salted fish and salted vegetables. Cooked rice, soybean paste soup, beef, cooked sliced radish strip, and yogurt were favorite foods, with steam being a favorite cooking method. Subjects considered nutrition as the most important factor for improving food service quality. CONCLUSIONS: Results of this study could be utilized for improving food-service for the residents in elderly care facilities, and provide a basis for setting reference intake of energy and nutrients of the elderly having very low activity levels.
Aged* ; Ascorbic Acid ; Calcium ; Cooking ; Dementia ; Diabetes Mellitus ; Dietary Fiber ; Energy Intake ; Energy Metabolism ; Female ; Fishes ; Food Preferences* ; Food Services ; Fruit ; Humans ; Hypertension ; Iron ; Male ; Meat ; Milk ; Motor Activity ; Niacin ; Nutrition Assessment ; Potassium ; Raphanus ; Recommended Dietary Allowances ; Riboflavin ; Shellfish ; Sodium ; Soybeans ; Steam ; Thiamine ; Vegetables ; Vitamin A ; Vitamin B 6 ; Vitamin E ; Vitamins ; Yogurt ; Zinc

BACKGROUNDLate-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown.

METHODSWe performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected.

RESULTSAfter 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time.

CONCLUSIONSOur results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

Adolescent ; Adult ; Age of Onset ; Child ; Cohort Studies ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Lipid Metabolism, Inborn Errors ; therapy ; Male ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; drug therapy ; Muscular Dystrophies ; therapy ; Riboflavin ; therapeutic use ; Young Adult

OBJECTIVETo identify pathogenic mutation in a boy affected with riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency (RR-MADD).

METHODSThe patient was initially diagnosed as primary carnitine deficiency (PCD) and has been treated with carnitine supplementation for 7 years. Clinical manifestations and characteristics of fibula muscle specimen were analyzed. Potential mutation in electron transfer flavoprotein dehydrogenase (ETFDH) gene (for the patient and his parents) and carnitine transfer protein gene (SLC22A5) (for the patient) was screened.

RESULTSElectronic microscopy of the muscle specimen has suggested lipid storage myopathy. Mutation analysis has found that the patient carried compound heterozygous mutations, c.250G>A and c.380T>C, in exon 3 of the ETFDH gene, whilst his father and mother were heterozygous for the c.380T>C and c.250G>A mutations, respectively. Screening of the SLC22A5 gene has yielded no clinically meaningful result. After the establishment of diagnosis of RR-MADD, the condition of the patient has improved greatly with supplementation of high doses of riboflavin along with continuous carnitine supplement.

CONCLUSIONThe c.250G>A (p.Ala84Thr) mutation of exon 3 of the ETFDH gene has been a hot spot in Southern Chinese population, whilst the c.380T>C (p.Leu127Pro) is rarely reported. Our case has suggested that therapeutic diagnosis cannot substitute genetic testing. The mechanism for having stabilized the patient with only carnitine supplementation for 7 years needs further investigation.

Adolescent ; Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Electron-Transferring Flavoproteins ; genetics ; metabolism ; Female ; Humans ; Iron-Sulfur Proteins ; genetics ; metabolism ; Male ; Molecular Sequence Data ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; enzymology ; genetics ; metabolism ; Muscle, Skeletal ; metabolism ; Organic Cation Transport Proteins ; genetics ; metabolism ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; metabolism ; Riboflavin ; metabolism ; Solute Carrier Family 22 Member 5

OBJECTIVETo explore the improvement effect of vitamins B1, B2, PP supplementation to the metabolism changes of carbohydrates, lipids, protein and energy in mice exposed to acute hypoxia.

METHODSFifty male Kunming mice were randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed corresponding diets for two weeks and then except the normal group were exposed to a simulated altitude of 6 000 meters for 8 hours. The changes of glucose, pyruvate, lactate, urea nitrogen, free fatty acids and beta-hydroxybutyric acid from serum, liver glycogen and blood adenosine triphosphate (ATP) concentration were measured.

RESULTSAfter being exposed to acute hypoxia, the mice glucose, liver glycogen, pyruvate, lactate, free fatty acids, beta-hydroxybutyric acid and urea nitrogen level were increased significantly (P < 0.05), while blood ATP concentration was decreased. In the vitamins B1, B2 and PP supplemented groups, these changes were improved.

CONCLUSIONThe significant changes in carbohydrate, lipid and protein metabolism were observed in mice exposed to acute hypoxia, and the supplementation of vitamins B1, B2 and PP was proved to be beneficial in improving some metabolic pathways. It is suggested that the supplemented dose of four times was good.

Animals ; Carbohydrate Metabolism ; Hypoxia ; metabolism ; physiopathology ; Lipid Metabolism ; Male ; Mice ; Niacinamide ; administration & dosage ; Proteins ; metabolism ; Riboflavin ; administration & dosage ; Thiamine ; administration & dosage ; Vitamin B Complex ; administration & dosage

This study was purposed to confirm the practical efficacy of reducing indicating germs suspended in plasma by riboflavin and photosensitized inactivation and to evaluate its influence on activation of apheresis platelet concentrates. The synergistic effects of riboflavin combined with ultraviolet irradiation on inactivation of germs were investigated by using Escherichia Coli (E. coli) and Staphylococcus Aureus (S. aureus) as Gram⁻ and Gram(+) indicating germs, respectively. The activation status of apheresis-platelet concentrates treated with riboflavin combined with ultraviolet irradiation was detected by flow cytometry. The results showed that when 50 μmol/L of riboflavin was combined with 6.2 J/ml of ultraviolet irradiation, the T/E ratios reached 1.42 for E. coli and 1.68 for S. Aureus, and reduction of E. Coli and S. Aureus were 3.87 Logs and 3.82 Logs respectively; the CD62p expression level on germ-inactivated platelets stored at 22 degrees C for 0 and 5 days were 4.92% and 36.18% respectively, which slightly increased as compared with controls (3.94% and 32.03)% (p < 0.05). It is concluded that combination of riboflavin with ultraviolet irradiation displays well synergistic effects which can reduce E. Coli and S. Aureus counts, but no significantly influence on platelets. The partial activation of liquid platelets mainly presents metabolism damage during storage, which is found at an acceptable level.
Blood Platelets ; metabolism ; Drug Carriers ; Gram-Negative Bacteria ; drug effects ; radiation effects ; Gram-Positive Bacteria ; drug effects ; radiation effects ; Humans ; P-Selectin ; blood ; Photosensitizing Agents ; pharmacology ; Platelet Count ; Plateletpheresis ; methods ; Riboflavin ; pharmacology ; Ultraviolet Rays

OBJECTIVETo explore metabolic changes after acute hypoxia and modulating effect of vitamins B₁, B₂, and PP supplementation in mice exposed to acute hypoxia.

METHODSFifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B₁, B₂, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles.

RESULTSThere were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B₁, B₂, and PP supplementation, all these metabolic changes gradually recovered.

CONCLUSIONSSignificant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B₁, B₂, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B₁, B₂, and PP should be increased under hypoxia condition.

Acute Disease ; Animals ; Dose-Response Relationship, Drug ; Hypoxia ; blood ; metabolism ; Lipid Metabolism ; drug effects ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; methods ; Mice ; Mice, Inbred Strains ; Niacinamide ; administration & dosage ; therapeutic use ; Nutritional Physiological Phenomena ; drug effects ; Principal Component Analysis ; Riboflavin ; administration & dosage ; therapeutic use ; Thiamine ; administration & dosage ; therapeutic use ; Vitamin B Complex ; administration & dosage ; therapeutic use

In Bacillus subtilis , raising the amount of carbon catabolite in vivo would lead to carbon catabolite repression (CCR) and restrain the absorption of glucose. By deleting CcpA the CCR effect could be relieved, but the absorption of glucose remains restrained. The phosphoenol-pyruvate-sugar phosphotransferase system (PTS) is the main glucose transportation system in B. subtilis. HPr protein together with HprK/P participate in the glucose transportation. The HPr protein is phosphorylated at His-15 forming HPr-His-15-P transferring phosphate group from HPr to E II . While HprK/P phosphorylate HPr at Ser-46 forming HPr-Ser-46-P. HPr-Ser-46-P cannot participate in the transportation of glucose. The Knockout of ccpA gene increases the amount of fructose 1,6-bisphosphate(FBP) in vivo. And FBP could activate HPr kinase. So when CcpA is deleted, most part of the HPr will be phosphorylated at Ser-46. Absorpton of glucose is blocked. In this study, by disruption of hprk gene, the obtained B. subtilisZHc/pMX45 reaches the peak riboflavin production of 4.374mg/mL at the optimum glucose concentration of 10%, 19.2% higher than that of B. subtilis24 A1/pMX45 at the optimum glucose concentration of 8%.
Bacillus subtilis ; metabolism ; Bacterial Proteins ; genetics ; physiology ; Fermentation ; Glucose ; metabolism ; Mutation ; Phosphoenolpyruvate Sugar Phosphotransferase System ; genetics ; physiology ; Riboflavin ; metabolism ; Sucrose ; metabolism

This study was conducted to investigate osteopenia and osteoporosis prevalence of radius and tibia using Quantitative Ultrasound (QUS) and to identify affecting factors of osteoporosis. A total of 4,340 women aged 40 - 69 years, living in Ansung (rural) and Ansan (mid-sized) area, and free of illnesses affecting bone metabolism participated in the community-based cohort study. Among them 4,059 subjects measured radius bone density and 4,089 measured tibia. The T-score threshold, defined as < -1.0 and < or = -2.5, was used to identify subjects with osteopenia and osteoporosis by WHO criteria. The crude prevalence of osteoporosis in radius and tibia was 8.4% and 23.3% respectively; after adjustment for age, it changed 6.3% and 18.8%. In simple logistic regression analysis, the prevalence of osteoporosis increased by aging, non-marital status, low education, low income. Otherwise, high intakes of Ca/P, thiamin, riboflavin, vitamin B6, and vitamin E were decreased osteoporosis prevalence. Compared to the normal BMI (body mass index) group (18.5 < or = BMI < 23), the odds ratio (ORs) of the low BMI group (BMI < 18.5), and high BMI groups (BMI 25 - 30, BMI > or = 30) were significantly increased. The OR of osteoporosis decreased across increasing quartiles of intakes of Ca, P and Ca/P. Therefore, maintaining normal BMI and increasing Ca intake and Ca/P ratio may have a beneficial effect on bone health of Korean women.
Aging ; Bone Density ; Bone Diseases, Metabolic ; Cohort Studies* ; Education ; Female ; Genome* ; Gyeonggi-do ; Humans ; Logistic Models ; Metabolism ; Odds Ratio ; Osteoporosis* ; Prevalence* ; Radius* ; Riboflavin ; Tibia* ; Ultrasonography* ; Vitamin B 6 ; Vitamin E ; Vitamins