[Investigation on the recommended dose of prebiotic in health food in China in 1996-2022].

OBJECTIVE: To understand the recommended dose distribution of prebiotic-containing health food in China. METHODS: The overall recommended dose of prebiotic health food was available from the label information of approved prebiotic health food from 1996 to 2022; the recommended dose distribution of prebiotic-containing health food was analyzed from different healthy functions and different ways of addition. RESULTS: There were 174 prebiotic-containing health food products with clear dose information, respectively, involving 5 prebiotics including Fructooligosaccharides, Galactooligosaccharides, Isomaltooligosaccharides, Xylo-oligosaccharides and Polydextrose, and the majority of prebiotics were added in combination, with 159 products. The recommended dose range of prebiotic-containing health food products was wide, and in general, the dose of prebiotic-containing health food products used alone was higher than the dose used in combination. The recommended daily intake range of health food containing Fructooligosaccharides was 5.28-17 500 mg/d, the recommended daily intake range of health food containing Isomaltooligosaccharides was 220-28 000 mg/d, the dose range of health food containing Xylo-oligosaccharides was 8.4-2 800 mg/d, the dose range of health food containing Polydextrose was 4-12 120 mg/d, the number of Galacto-Oligosaccharides products Only two kinds of products were included, with doses of 259.8 mg/d and 3500 mg/d, respectively. The claimed functions of prebiotic health food products were focused on laxative function, immunity enhancement, and regulation of intestinal flora. The application dose of prebiotic health food with different functional compounding additions was close to the overall dose. CONCLUSION: The recommended dosage range of prebiotics in health food containing prebiotics in China is large, and prebiotics in products are mainly added by compounding.

Characterization of the gut microbiota and fecal and blood metabolomes under various factors in urban children from Northwest China.

Introduction: Children have regional dynamics in the gut microbiota development trajectory. Hitherto, the features and influencing factors of the gut microbiota and fecal and plasma metabolites in children from Northwest China remain unclear. Methods: Shotgun metagenomic sequencing and untargeted metabolomics were performed on 100 healthy volunteers aged 2-12 years. Results: Age, body mass index (BMI), regular physical exercise (RPE), and delivery mode (DM) significantly affect gut microbiota and metabolites. Lactobacillus, Butyricimonas, Prevotella, Alistipes, and predicted pathway propanoate production were significantly increased with age while Bifidobacterium breve, B. animalis, B. pseudocatenulatum, Streptococcus infantis, and carbohydrate degradation were decreased. Fecal metabolome revealed that the metabolism of caffeine, amino acids, and lipid significantly increased with age while galactose metabolism decreased. Noticeably, BMI was positively associated with pathogens including Erysipelatoclostridium ramosum, Parabacteroides distasonis, Ruminococcus gnavus, and amino acid metabolism but negatively associated with beneficial Akkermansia muciniphila, Alistipes finegoldii, Eubacterium ramulus, and caffeine metabolism. RPE has increased probiotic Faecalibacterium prausnitzii and Anaerostipes hadrus, acetate and lactate production, and major nutrient metabolism in gut and plasma, but decreased pathobiont Bilophila wadsworthia, taurine degradation, and pentose phosphate pathway. Interestingly, DM affects the gut microbiota and metabolites throughout the whole childhood. Bifidobacterium animalis, Lactobacillus mucosae, L. ruminis, primary bile acid, and neomycin biosynthesis were enriched in eutocia, while anti-inflammatory Anaerofustis stercorihominis, Agathobaculum butyriciproducens, Collinsella intestinalis, and pathogenic Streptococcus salivarius, Catabacter hongkongensis, and amino acid metabolism were enriched in Cesarean section children. Discussion: Our results provided theoretical and data foundation for the gut microbiota and metabolites in preadolescent children's growth and development in Northwest China.

Multiomics Revealed the Multi-Dimensional Effects of Late Sleep on Gut Microbiota and Metabolites in Children in Northwest China.

Background Sleep plays a pivotal role in children's mental and physical development and has been linked to the gut microbiota in animals and adults. However, the characteristics of the gut microbiota and metabolites and the relationship to late bedtimes in children remain unclear. Methods In total, 88 eligible children, aged from 3 to 8 years, were recruited and divided into two groups according to the bedtime collected by designed questionnaires (early, before 22:00: n = 48; late, after 22:00, n = 40). Stools and plasma samples were collected to examine the characteristics of the gut microbiota and metabolites by shotgun metagenomics and metabolomics. Results The richness and diversity of the gut microbiota in children with early bedtime were significantly increased compared with the late ones. Coprococcus, Collinsella, Akkermansia muciniphila, and Bifidobacterium adolescentis were significantly more abundant in children with early bedtime, while Bacteroides and Clostridium sp. CAG-253 were obviously enriched in the late ones. A total of 106 metabolic pathways, including biosynthesis of ribonucleotide, peptidoglycan, and amino acids, and starch degradation were enriched in children with early bedtime, while 42 pathways were abundant in those with late bedtime. Notably, more gut microbial metabolites were observed in children with late bedtime, which included aldehyde, ketones, esters, amino acids and their metabolites, benzene and substituted derivatives, bile acids, heterocyclic compounds, nucleotide and metabolites, organic acid and derivatives, sugars and acyl carnitine. In plasma, fatty amides, lipids, amino acids, metabolites, hormones, and related compounds were enriched in children with early bedtime, while bile acids were higher in children with late bedtime. Association studies revealed that the different microbial species were correlated with metabolites from gut microbiota and plasma. Conclusions The results of our study revealed that the gut microbiota diversity and richness, and metabolic pathways were significantly extensive in children with early bedtime, whereas the gut microbial metabolites were significantly decreased, which might be related to gut microbial differences.

[Comparative study on the essential composition content of commercial follow-up formula for older infant with the requirements in the new national food safety standard in China from 2017 to 2022].

OBJECTIVE: To understand the distribution of the content range of essential ingredients in commercial follow-up formula for older infants in China, analyze the differences between the content of essential ingredients in commercial older infant formula milk powder in China and the requirements of the new national standard(GB 10766-2021). METHODS: The label information of 478 commercial follow-up formula for older infant registered and approved from January 2017 to June 2022 were collected and entered. The distribution of essential ingredients was statistically analyzed, which was compared with the requirements of the new national food safety standard. RESULTS: The new national standard has 31 essential components. Compared with the old national standard(GB 10767-2010), five indicators of carbohydrate, α-linolenic acid, choline, selenium and manganese were added. The new national standard has 28 essential component requirements revised, including 13 adjusted the lower limit, 7 adjusted the upper limit, and 16 essential components added the upper limit. Among the approved 478 older infant formula milk powders, the distribution of 11 essential ingredients were all in line with the new national standard, and 14 essential ingredients were less than the lower limit of the new national standard. The essential ingredients whose minimum value was less than the lower limit of the new national standard and the proportion exceeds 50% were vitamin D, iodine and choline. with the proportions(number of cases) of 98.33%(470 cases), 74.06%(354 cases) and 72.37%(275 cases), respectively. The maximum value of essential ingredients exceeded the maximum requirements stipulated in the new national standard, and the protein in 13.18%(63 cases) of the older infant formula milk powder was higher than the maximum requirements of the new national standard. CONCLUSION: The content of essential components in most commercial products in China meets the new national standard requirements. Some essential ingredients need to be adjusted.

[Investigation on the addition of microbial food cultures in infant and follow-up formula in China from 2017 to 2022].

OBJECTIVE: To understand the addition of microbial food cultures in infant and follow-up formula milk powder in China. METHODS: The product information of infant and follow-up formula milk powder approved in China from 2017 to 2022 was investigated, including the query platform and packaging label information, and the strains, addition rates and addition amount of microbial food cultures were statistically analyzed. RESULTS: From 2017 to 2022, a total of 1438 infant and follow-up formula milk powder products were approved in China, of which 434 products were added with microbial food cultures, 6 types of strains were used, namely Bifidobacterium animalis Bb-12, Bifidobacterium lactis HN019, Bifidobacterium lactis Bi-07, Lactobacillus fermentum CECT5716, Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM, the top three addition rates were Bifidobacterium animalis Bb-12, Bifidobacterium lactis HN019 and Bifidobacterium lactis Bi-07, the addition rate were 79.72%, 18.43% and 12.67%, respectively. The addition amount of the strains ranged from 1×10~6 to 6×10~7 CFU/g, the median value was 1×10~6 CFU/g. CONCLUSION: There is insufficient scientific evidence on the feeding effect, types and amounts of microbial food cultures added to infant and follow-up formula in China.

On-line identification of the chemical constituents of Polygoni Multiflori Radix by UHPLC-Q-ToF MS/MS.

Introduction: Polygoni Multiflori Radix (PMR) is a type of Chinese herbal medicine with rich chemical composition and pharmacological activity used widely in medicine and food. However, in recent years, there have been increasing numbers of negative reports about its hepatotoxicity. Identification of its chemical constituents for quality control and safe use is very important. Methods: Three solvents of different polarities (water, 70% ethanol, and 95% ethanol solution) were used to extract the compounds from PMR. Extracts were analyzed and characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-ToF MS/MS) in the negative-ion mode. Results: 152 compounds were detected and identified: 50 anthraquinones, 33 stilbene derivatives, 21 flavonoids, seven naphthalene compounds, and 41 other compounds. Eight other compounds were reported for the first time in the PMR-related literature, and eight other compounds were potentially new compounds. Discussion: This study lays a solid foundation for the screening of toxicity and quality-control indicators of PMR.

CRISPR/Cas12a-based MUSCA-PEC strategy for HSV-1 assay.

In the photoelectrochemical sensing, constant potential excitation to get the photoelectrochemical signal is the main excitation signal mode. Novel method for photoelectrochemical signal obtaining is needed. Inspired by this ideal, a photoelectrochemical strategy for Herpes simplex virus (HSV-1) detection with multiple potential step chronoamperometry (MUSCA) pattern was fabricated using CRISPR/Cas12a cleavage coupled with entropy-driven target recycling. In the presence of target, HSV-1, the Cas12a was activated by the H1-H2 complex obtained by entropy-driven, then digesting the circular fragment of csRNA to expose single-stranded crRNA2 and alkaline phosphatase (ALP). The inactive Cas12a was self-assembled with crRNA2 and activated again with the help of assistant dsDNA. After multiple rounds of CRISPR/Cas12a cleavage and magnetic separation, MUSCA, as a signal amplifier, collected the enhanced photocurrent responses generated by catalyzed p-Aminophenol (p-AP). Different from the reported signal enhancement strategies based on photoactive nanomaterials and sensing mechanisms, MUSCA technique endowed the strategy with unique advantages of direct, fast and ultrasensitive. A superior detection limit of 3 aM toward HSV-1 was achieved. This strategy was successfully applied for HSV-1 detection in Human serum samples. The combination of MUSCA technique and CRISPR/Cas12a assay brings broader potential prospect for the detection of nucleic acids.

Integrated Metabolomic and Transcriptomic Analyses Reveal the Basis for Carotenoid Biosynthesis in Sweet Potato (Ipomoea batatas (L.) Lam.) Storage Roots.

Carotenoids are important compounds of quality and coloration within sweet potato storage roots, but the mechanisms that govern the accumulation of these carotenoids remain poorly understood. In this study, metabolomic and transcriptomic analyses of carotenoids were performed using young storage roots (S2) and old storage roots (S4) from white-fleshed (variety S19) and yellow-fleshed (variety BS) sweet potato types. S19 storage roots exhibited significantly lower total carotenoid levels relative to BS storage roots, and different numbers of carotenoid types were detected in the BS-S2, BS-S4, S19-S2, and S19-S4 samples. ß-cryptoxanthin was identified as a potential key driver of differences in root coloration between the S19 and BS types. Combined transcriptomic and metabolomic analyses revealed significant co-annotation of the carotenoid and abscisic acid (ABA) metabolic pathways, PSY (phytoene synthase), CHYB (ß-carotene 3-hydroxylase), ZEP (zeaxanthin epoxidase), NCED3 (9-cis-epoxycarotenoid dioxygenase 3), ABA2 (xanthoxin dehydrogenase), and CYP707A (abscisic acid 8'-hydroxylase) genes were found to be closely associated with carotenoid and ABA content in these sweet potato storage roots. The expression patterns of the transcription factors OFP and FAR1 were associated with the ABA content in these two sweet potato types. Together, these results provide a valuable foundation for understanding the mechanisms governing carotenoid biosynthesis in storage roots, and offer a theoretical basis for sweet potato breeding and management.

Exploratory Quality Control Study for Polygonum multiflorum Thunb. Using Dinuclear Anthraquinones with Potential Hepatotoxicity.

In recent years, the hepatotoxicity of Polygoni Multiflora Radix (PMR) has attracted increased research interest. Some studies suggest that anthraquinone may be the main hepatotoxic component. Most of the relevant studies have focused on the mononuclear anthraquinone component rather than binuclear anthraquinones. The hepatotoxicity of dinuclear anthraquinone (dianthrone) was investigated in a cell-based model. Next, a method for the determination of six free and total dianthonones in PMR and PMR Praeparata (PMRP) was established using ultra-high-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS), which was then used to analyze the collected samples. The data show that four binuclear anthraquinone compounds were hepatotoxic and may be potential toxicity indicators for the safety evaluation of PMR and PMRP. Herein, we provide a theoretical basis for the improvement of PMRP quality standards.

A stepwise strategy integrating metabolomics and pseudotargeted spectrum-effect relationship to elucidate the potential hepatotoxic components in Polygonum multiflorum.

Polygonum multiflorum (PM) Thunb., a typical Chinese herbal medicine with different therapeutic effect in raw and processed forms, has been used worldwide for thousands of years. However, hepatotoxicity caused by PM has raised considerable concern in recent decades. The exploration of toxic components in PM has been a great challenge for a long time. In this study, we developed a stepwise strategy integrating metabolomics and pseudotargeted spectrum-effect relationship to illuminate the potential hepatotoxic components in PM. First, 112 components were tentatively identified using ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Second, based on the theory of toxicity attenuation after processing, we combined the UPLC-Q-TOF-MS method and plant metabolomics to screen out the reduced differential components in PM between raw and processed PM. Third, the proposed pseudotargeted MS of 16 differential components was established and applied to 50 batches of PM for quantitative analysis. Fourth, the hepatocytotoxicity of 50 batches of PM was investigated on two hepatocytes, LO2 and HepG2. Last, three mathematical models, gray relational analysis, orthogonal partial least squares analysis, and back propagation artificial neural network, were established to further identify the key variables affecting hepatotoxicity in PM by combining quantitative spectral information with toxicity to hepatocytes of 50 batches of PM. The results suggested that 16 components may have different degrees of hepatotoxicity, which may lead to hepatotoxicity through synergistic effects. Three components (emodin dianthrones, emodin-8-O-ß-D-glucopyranoside, PM 14-17) were screened to have significant hepatotoxicity and could be used as toxicity markers in PM as well as for further studies on the mechanism of toxicity. Above all, the study established an effective strategy to explore the hepatotoxic material basis in PM but also provides reference information for in-depth investigations on the hepatotoxicity of PM.

Integrated spatially resolved metabolomics and network toxicology to investigate the hepatotoxicity mechanisms of component D of Polygonum multiflorum Thunb.

ETHNOPHARMACOLOGICAL RELEVANCE: The liver toxicity of Reynoutria multiflora (Thunb.) Moldenke. (Polygonaceae) (Polygonum multiflorum Thunb, PM) has always attracted much attention, but the related toxicity materials and mechanisms have not been elucidated due to multi-component and multi-target characteristics. In previous hepatotoxicity screening, different components of PM were first evaluated and the hepatotoxicity of component D [95% ethanol (EtOH) elution] in a 70% EtOH extract of PM (PM-D) showed the highest hepatotoxicity. Furthermore, the main components of PM-D were identified and their hepatotoxicity was evaluated based on a zebrafish embryo model. However, the hepatotoxicity mechanism of PM-D is unknown. AIM OF THE STUDY: This work is to explore the hepatotoxicity mechanisms of PM-D by integrating network toxicology and spatially resolved metabolomics strategy. MATERIALS AND METHODS: A hepatotoxicity interaction network of PM-D was constructed based on toxicity target prediction for eight key toxic ingredients and a hepatotoxicity target collection. Then the key signaling pathways were enriched, and molecular docking verification was implemented to evaluate the ability of toxic ingredients to bind to the core targets. The pathological changes of liver tissues and serum biochemical assays of mice were used to evaluate the liver injury effect of mice with oral administration of PM-D. Furthermore, spatially resolved metabolomics was used to visualize significant differences in metabolic profiles in mice after drug administration, to screen hepatotoxicity-related biomarkers and analyze metabolic pathways. RESULTS: The contents of four key toxic compounds in PM-D were detected. Network toxicology identified 30 potential targets of liver toxicity of PM-D. GO and KEGG enrichment analyses indicated that the hepatotoxicity of PM-D involved multiple biological activities, including cellular response to endogenous stimulus, organonitrogen compound metabolic process, regulation of the apoptotic process, regulation of kinase, regulation of reactive oxygen species metabolic process and signaling pathways including PI3K-Akt, AMPK, MAPK, mTOR, Ras and HIF-1. The molecular docking confirmed the high binding activity of 8 key toxic ingredients with 10 core targets, including mTOR, PIK3CA, AKT1, and EGFR. The high distribution of metabolites of PM-D in the liver of administrated mice was recognized by mass spectrometry imaging. Spatially resolved metabolomics results revealed significant changes in metabolic profiles after PM-D administration, and metabolites such as taurine, taurocholic acid, adenosine, and acyl-carnitines were associated with PM-D-induced liver injury. Enrichment analyses of metabolic pathways revealed tht linolenic acid and linoleic acid metabolism, carnitine synthesis, oxidation of branched-chain fatty acids, and six other metabolic pathways were significantly changed. Comprehensive analysis revealed that the hepatotoxicity caused by PM-D was closely related to cholestasis, mitochondrial damage, oxidative stress and energy metabolism, and lipid metabolism disorders. CONCLUSIONS: In this study, the hepatotoxicity mechanisms of PM-D were comprehensively identified through an integrated spatially resolved metabolomics and network toxicology strategy, providing a theoretical foundation for the toxicity mechanisms of PM and its safe clinical application.

Pharmacokinetics and metabolism of trans-emodin dianthrones in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. (PM) is a common traditional Chinese medicine with diverse biological activities of resolving toxins, nourishing livers and promoting hairs. Nevertheless, in recent years hepatotoxic adverse reactions caused by the administration of PM have raised worldwide concerns. In our previous study, we found that emodin dianthrones showed hepatotoxicity and may be potential toxicity markers. However, the metabolic transformation and pharmacokinetic behavior of emodin dianthrones in vivo have still not been elucidated. AIM OF THE STUDY: Taking trans-emodin dianthrones (TED) as an example, the present study was conducted to investigate the pharmacokinetics and bioavailability of TED in rats and characterized its metabolic transformation in the plasma, urine and feces of rats. MATERIALS AND METHODS: A rapid and sensitive UPLC-qqq-MS/MS method was developed for accurate quantification of TED in plasma and successfully applied to the pharmacokinetic evaluation of TED in rats after intravenous and oral administration. A reliable UFLC-Q-TOF-MS high resolution mass spectrometry combined with a scientific metabolite identification strategy was used to comprehensively characterize the metabolic transformation of TED in plasma, urine and feces in rats. RESULTS: The established UPLC-qqq-MS/MS method had a linear range of 1-500 ng/mL, and the method was accurate and reliable to meet the quantitative requirements. When 20 mg/kg TED was given by gavage rats, it was rapidly absorbed into the circulatory system and had a long half-life time of 6.44 h and wide tissue distribution in vivo. While intravenous injection of 0.4 mg/kg TED in rats, it was rapidly metabolized and eliminated with a half-life time of 1.82 h. The oral absorption bioavailability of TED was only 2.83%. Furthermore with a sensitive UFLC-Q-TOF-MS technique and metabolite identification strategy, 21 metabolites were successfully identified, including 11 in plasma, 12 in urine and 18 in feces. The main Ⅰ and Ⅱ phase metabolic processes involved glucuronidation, oxidation, carbonylation, (de)methylation, sulfation and hydrogenation. CONCLUSION: TED could be rapidly absorbed into the blood circulation and widely distributed and slowly metabolized in the body and underwent extensive cleavage and metabolic transformation in vivo. The study provided a basis for in-depth elucidation of the toxicology and mechanism research of TED, but also laid the foundation for further research on the material basis of hepatotoxicity of PM.

Cyclic coupling of photocatalysis and adsorption for completely safe removal of N-nitrosamines in water.

The incomplete removal of N-nitrosamines in water through current degraded techniques and the carcinogenicity of N-nitrosamines call for alternative complete and safe removal approaches. Here, we describe a cyclic coupling process of photocatalysis and adsorption enabling N-nitrosamines in water thoroughly and safely removed. Among them, the immobilized TiO2/Ti photocatalyst degraded N-nitrosamines into primary and secondary amines up to 100% by attacking on nitrosyl nitrogen via •OH originated from its nanowire film morphology. Furthermore, the affinity of HY zeolite to primary and secondary amines led to efficient adsorption through corresponding to Lagergren adsorption rate equation of second order. And then the cyclic coupling process of photocatalysis and adsorption realized complete and safe removal of N-nitrosamines with various concentration ranging from 0.1 mM to 1 mM in water, significantly higher than the existing reports on the removal rate of N-nitrosamines and the formation potential of N-nitrosamines. This study will lead to new avenues for complete and safe eliminaton of hardly degradable hazardous substances in water.

Exploration on Optimized Control Way of D-Amino Acid for Efficiently Mitigating Membrane Biofouling of Membrane Bioreactor.

The thorny issue of membrane biofouling in membrane bioreactors (MBR) calls for new effective control measures. Herein, D-amino acid (DAA) was employed to mediate MBR membrane biofouling by inhibiting biofilm information and disintegrating formed biofilm. Different DAA control ways involving membrane property, DAA-adding timing, and DAA-control mode were explored through experiments and the multiple linear regression model and the response surface methodology. The optimized DAA control ways were acquired, involving DAA used as an active agent, and the DAA-adding timing of 4 h cultured before running, as well as both hydrophilic and hydrophobic membrane, resulting in an approximately 40.24% decrease in the membrane biofouling rate in comparison with the conventional MBR. DAA is an efficient membrane biofouling mediating approach for MBR under optimized control ways combination and a facile solution for solving membrane biofouling in actual membrane systems.

UHPLC-QQQ-MS/MS assay for the quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: applications for the standardization of traditional Chinese medicines (TCMs) with endogenous toxicity.

BACKGROUND: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researchers to explore methods to improve quality standards to ensure their quality and treatment effects. METHODS: In the present study, an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was optimized and validated for the determination of dianthrones in PMR and PMRP using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase [A: acetonitrile and B: water containing 0.1% formic acid (v/v)] at a flow rate of 0.25 mL/min was achieved on an Agilent ZORBAX SB-C18 column (2.1 mm × 50 mm, 1.8 µm). The triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Moreover, compounds 5 and 6 were further evaluated for their cytotoxicity in HepaRG cells by CCK-8 assay. RESULTS: The UHPLC-QQQ-MS/MS method was first developed to simultaneously determine six dianthrones in PMR and PMRP, namely, polygonumnolides C1-C4 (1-4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1-6 in 90 batches of PMR were in the ranges of 0.027-19.04, 0.022-13.86, 0.073-15.53, 0.034-23.35, 0.38-83.67 and 0.29-67.00 µg/g, respectively. The contents of 1-6 in 86 batches of commercial PMRP were in the ranges of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030-12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. Compounds 1-4 were almost completely eliminated after reasonable processing for 24 h and the contents of compounds 5 and 6 significantly decreased. Additionally, compounds 5 and 6 showed inhibitory activity in HepaRG cells with IC50 values of 10.98 and 15.45 µM, respectively. Furthermore, a systematic five-step strategy to standardize TCMs with endogenous toxicity was proposed for the first time, which involved the establishment of determination methods, the identification of potentially toxic markers, the standardization of processing methods, the development of limit standards and a risk-benefit assessment. CONCLUSION: The results of the cytotoxicity evaluation of the dianthrones indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as toxic markers of PMRP. Taking PMR and PMRP as examples, we hope this study provides insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in the future.

[Fast determination of mineral elements in wheat flour by near-infrared spectroscopy].

OBJECTIVE: Near-infrared(NIR) spectroscopy combined with partial least squares(PLS) were applied to establish a rapid method for green direct determination of mineral elements(calcium, phosphorus and potassium) in wheat flour samples. METHODS: NIR spectra and analytical measurements of calcium, phosphorus and potassium were collected from 117 wheat flour samples with different processing levels(whole grain wheat, special grade No. 1 wheat and wheat core flour). Principal components analysis(PCA) was developed to assign 81 wheat flour samples to build models and 36 samples as the validation set to evaluate the performance of the developed models. The influence of wavelength range and spectral preprocessing method on the predictive ability of the model were discussed, and the best models were selected. RESULTS: For calcium, the best NIR model showed a good prediction performance(r~2=0. 7907, RMSEP=5. 35, RPD=2. 19); the best NIR model for phosphorus gave an excellent prediction performance(r~2=0. 9777, RMSEP=15. 3, RPD=6. 71); the best model for potassium also gave an excellent prediction performance(r~2=0. 9777, RMSEP=18. 9, RPD=6. 84). CONCLUSION: NIR spectroscopy can realize the rapid prediction of mineral elements(calcium, phosphorus and potassium) in wheat flour. By selecting the wavelength range and spectral preprocessing method, the prediction ability of the NIR model can be significantly improved.

Advances in Understanding the Metabolites and Metabolomics of Polygonum multiflorum Thunb: A Mini-review.

BACKGROUND: The roots of Polygonum multiflorum (PM) are a well-known traditional Chinese medicine, widely used to treat a variety of conditions in Southeast Asia, South Korea, Japan and other countries. It is known that Polygoni Multiflori Radix Praeparata (PMRP) may enhance the efficacy and reduce the toxicity of PM. However, reports of adverse reactions, such as hepatotoxicity, caused by PM or PMRP, have continuously appeared around the world, which increased the known risks of the medication and gradually gained the extensive attention of many researchers. The chemical constituents of PM that cause hepatotoxicity have not been distinctly elucidated using the traditional phytochemical screening. Recently, with the rapid development of metabolomics, there has been a growing need to explore the potential hepatotoxic components and mechanisms of PM. METHODS: The metabolites and metabolomics of PM were searched by the Web of Science, PubMed, Google scholar and some Chinese literature databases. RESULTS: A brief description of metabolites and metabolomics of PM is followed by a discussion on the metabolite- induced toxicity in this review. More than 100 metabolites were tentatively identified and this will contribute to further understanding of the potential hepatotoxic components of PM. Meanwhile, some toxic compounds were identified and could be used as potential toxic markers of PM. CONCLUSION: This review mainly outlines the metabolites and metabolomics of PM that have been identified in recent years. This study could help to clarify the potential hepatotoxic components and metabolic mechanisms of PM and provide a scientific reference for its safe clinical use in the future.

In vivo hepatotoxicity screening of different extracts, components, and constituents of Polygoni Multiflori Thunb. in zebrafish (Danio rerio) larvae.

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-ß-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

Multiflorumisides HK, stilbene glucosides isolated from Polygonum multiflorum and their in vitro PTP1B inhibitory activities.

A phytochemical study on a 70% EtOH extract of dried roots of Polygonum multiflorum resulted in the isolation of four undescribed stilbene glucosides, namely multiflorumisides HK (1-4). The structures of the natural products were elucidated by 1D and 2D nuclear magnetic resonance (NMR) as well as mass spectroscopy analyses. Among them, multiflorumiside J (3) and multiflorumiside K (4) belong to rare tetramer stilbene glucosides. Moreover, the in vitro inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) were evaluated and the putative biosynthetic pathway was proposed. Notably, compounds 1-4 showed the inhibitory activity against PTP1B with the IC50 values of 1.2, 1.7, 1.5 and 4.6 µm, respectively. Based on the obtained results, stilbene glucosides could be the potential PTP1B inhibitors of P. multiflorum.

Effects of fish oil supplementation on glucose control and lipid levels among patients with type 2 diabetes mellitus: a Meta-analysis of randomized controlled trials.

BACKGROUND: Previous studies have yielded inconsistent findings on the role of fish oil in type 2 diabetes mellitus (T2DM). We systematically summarized the available evidence from randomized controlled trials (RCT) and aimed to investigate the effects of fish oil supplementation on glucose control and lipid levels among patients with T2DM. METHODS: A comprehensive literature search was performed in electronic databases (PubMed, ProQuest, Cochrane Library, CNKI, VIP, and Wanfang) to identify all relevant RCTs which were published up to May 31st, 2019. We used Modified Jadad Score system to evaluate the quality of each included RCT. The pooled effects were estimated using random-effects model and presented as standardized mean differences with 95% confidence intervals. RESULTS: A total of 12 RCTs were included in this meta-analysis. There was no significant difference in glucose control outcomes comparing fish oil supplementation to placebo. The effect size of fasting plasma glucose (FPG) was 0.13 (95% CI: - 0.03 to 0.28, p > 0.05). No marked change was observed in fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and HOMA of insulin resistance (HOMA-IR) levels. Fish oil supplementation was associated with a decrease of triglyceride (TG) level by - 0.40 (95%CI: - 0.53 to - 0.28, p < 0.05), and an increase of high density lipoprotein (HDL) cholesterol level by 0.21 (95%CI: 0.05 to 0.37, p < 0.05). In subgroup analysis, HDL cholesterol level was higher among Asian and low-dose(< 2 g/d n-3 PUFA) subgroups compared to their counterparts (p < 0.05). TG level was lower in mid and long duration groups, along with an inconspicuous difference in short duration group. CONCLUSIONS: This meta-analysis shows that among patients with T2DM, fish oil supplementation leads to a favorable blood lipids profile but does not improve glucose control.