Resultant compound from sublimation test for Gentianae Radix in Japanese Pharmacopoeia was 5-(hydroxymethyl)furfural.

Gentianae Radix, an herbal medicine, has been used as a gastrointestinal drug in Japan. In the Japanese Pharmacopoeia 18th Revision, the sublimation test is specified as an identification test for Gentianae Radix. The compound obtained in this sublimation test was believed to be gentisin, a xanthone family compound. However, the compound we identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and 1H- and 13C-NMR was 5-(hydroxymethyl)furfural (5-HMF). The same compound was found to be a sublimate of Gentianae Scabrae Radix and Gentianae Macrophyllae Radix, belonging to the same genus as Gentianae Radix. These results indicate the necessity to revise the identification test for Gentianae Radix to a more unique method.

A chemometric study on the identification of 5-methylfurfural and 2-acetylfuran as particular volatile compounds of oxidized fish oil based on SHS-GC-IMS.

Fish oil develops particular off-odors, mainly fishy odor, from the oxidation of its characteristic fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA). Anchovy oil (AO) was taken as representative of fish oils. This was compared to three vegetable oils with different fatty acid compositions, i.e. camellia, sunflower and linseed oil, and differential volatile compounds were identified by static-headspace gas-chromatography ion-mobility-spectrometry (SHS-GC-IMS) and orthogonal partial-least-squares discriminant analysis (OPLS-DA) during oxidation at 60 °C. Three groups of differential volatile compounds detected at higher concentrations in the AO were screened out and two compounds, identified as 5-methylfurfural and 2-acetylfuran, were characteristic to the AO and not found in the vegetable oils. They were formed from both EPA and DHA, only present in the AO, and their formation mechanisms were proposed. The contents of 5-methylfurfural and 2-acetylfuran increased linearly with the oxidation time and consequently they could be used as oxidative markers of fish oils.

Impact of Different Storage Regimes on the Levels of Physicochemical Characteristics, Especially Free Acidity in Talh (Acacia gerrardii Benth.) Honey.

This study investigates how storage conditions (temperature and duration) may affect the physicochemical parameters, especially free acidity (FA), of Talh honey originating from Acacia gerrardii that have naturally high FA levels. Fresh Talh honey samples were kept at 0, 25, 35, and 45 °C, and analyzed monthly over a period of eight months. The Talh honey was monofloral with 69% A. gerrardii pollen content. The free acidity (FA) of freshly harvested Talh honey samples was higher (93 ± 0.3 meq/kg) than that of standard limits (≤50 meq/kg) and remained stable at 0 °C throughout the storage period. A significantly increase in FA started to occur after storage for 6 months at 25 °C (103 ± 0.2 meq/kg), 2 months at 35 °C (108 ± 0.3 meq/kg), and 1 month at 45 °C (112 ± 0.3 meq/kg). After 8 months of storage, the highest FA level was recorded at 45 °C (159 ± 0.5 meq/kg), followed by 127 ± 0.3 meq/kg at 35 °C, 105 ± 0.2 meq/kg at 25 °C, and 94 ± 0.3 meq/kg at 0 °C. It was found that 0 °C was an appropriate temperature for storing honey for long time. The electrical conductivity (EC) of fresh Talh samples (1.46 ± 0.0 mS/cm) was above the accepted limit (≤0.8 mS/cm), which was slightly increased (non-significant) throughout the storage period under all the storage temperatures. Hydroxymethylfurfural (HMF), diastase activity (DN), and reducing sugars (RSs) showed normal levels only at 0 °C and 25 °C throughout the storage period. However, HMF exceeded the standard limits after the first month at 45 °C (127 ± 9.6 mg/kg) and after the second month at 35 °C (90 ± 23.5 mg/kg), DA decreased below standard limits after the second month (5 ± 1 DN) under 45 °C and after the seventh month under 35 °C (7 ± 2 DN, and RSs decreased below 60% after 2 months under 45 °C and after 6 months at 35 °C. The physicochemical parameters (moisture content, pH, color, and sucrose) were the least affected and were within the standard range throughout the storage period under all the storage temperatures. The levels of FA and EC in fresh Talh samples were higher than the acceptable limits. The moisture content, pH, color, and sucrose content were not affected by storage conditions and remained within the acceptable limits. HMF, DA, and RSs were significantly affected by storage conditions only at 35 and 45 °C. The storage of honey at low temperatures (0 and 25 °C) for up to eight months presented the least amount of changes in the honey, and the honey was unchanged from its fresh status. Honey storage at 35 and 45 °C resulted in significant changes. It is recommended that Talh honey, which normally has high acidity levels, should be stored at temperatures not exceeding 25 °C.

[Optimization of processing technology of braised Rehmanniae Radix based on multiple indexes and response surface technology and correlation between components and color].

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.

Soluble dietary fiber from tea residues with inhibitory effects against acrylamide and 5-hydroxymethylfurfural formation in biscuits: The role of bound polyphenols.

This study investigated the impact of soluble dietary fiber (SDF) from untreated (U-SDF), fermented (F-SDF) and high temperature cooked (H-SDF) from tea residues on formation of acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) in biscuits. Both 3% F-SDF and 2% H-SDF can simultaneously inhibit AA and 5-HMF and SDFs increased the types of volatile compounds in biscuits. After the determination of the bound polyphenol compositions in SDFs by LC-QTOF-MS/MS, six polyphenols with different structural characteristics were selected to explore their contributions on the inhibitory effect of SDFs and structure-inhibitory capacity relationships in the "glucose-asparagine-linoleic acid" model system. It showed that the inhibitory activities of those polyphenols were greatly affected by the number of hydroxyl groups and methoxy groups on the benzene ring. Almost all polyphenols were also found to scavenge hydroxyl radicals generated in reactions. Thus, this study suggests that the bound polyphenols of SDFs play a key role in the inhibition of AA and 5-HMF.

The role of 5-hydroxymethylfurfural in food and recent advances in analytical methods.

The thermal processing, storage, and transportation of foodstuffs (e.g., fruit juices, coffee, honey, and vinegar) generate 5-hydroxymethylfurfural (HMF). The food industry uses this compound as a quality marker, thus increasing the demand for fast and reliable analytical methods for its determination. This review focuses on the formation of HMF in food, its desirable and toxic effects, and recent advances in analytical methods for its determination in foodstuffs. The advantages and limitations of these analytical approaches are discussed relative to the main analytical features.

Determination of 5-hydroxymethylfurfural using an electropolymerized molecularly imprinted polymer in combination with Salle.

Coffee, a beverage with a complex chemical composition, is appreciated for the sensory experience of its taste and aroma. The compound 5-(hydroxymethyl)-2-furfural (HMF) is essential for sensory characterization of the beverage, and is also used in the traceability of its production. In this work, a procedure combining salting-out assisted liquid-liquid extraction (SALLE) and an electropolymerized molecularly imprinted polymer (e-MIP) was developed for the detection and quantification of HMF in coffee samples. The sample preparation step using SALLE employed a combination of acetonitrile and phosphate-buffered saline, in a proportion of 70:30 (ACN:PBS), with addition of 0.02 g of NaCl. The new sensor (e-MIP) was prepared by electropolymerization of p-aminobenzoic acid onto a glassy carbon electrode (GCE) using cyclic voltammetry (CV). Analytical determinations were performed by differential pulse voltammetry (DPV). The linear regression correlation coefficient (r2) for the response was 0.9986. The limits of detection and quantification were 0.372 mg L-1 and 1.240 mg L-1, respectively. The repeatability and reproducibility values obtained were 6 and 10%, respectively. The recoveries for three concentration levels were between 97 and 101%. Analyses of different coffee samples showed that the HMF concentrations varied from 261.0 ± 41.0 to 770.2 ± 55.9 mg kg-1 in powdered coffee samples, and from 1510 ± 50 to 4445 ± 278 mg kg-1 in instant coffee samples. The advantages of this procedure, compared to other methods described in the literature, are its simplicity, easy operation, good selectivity and sensitivity, low cost, and minimal use of organic solvents.

Preparation of 5-hydroxymethylfurfural from Schisandra chinensis (Turcz.) Baill by high-speed counter-current chromatography: Comparison of conventional and consecutive separation.

Schisandra chinensis is a plant with high medicinal value, which contains many medicinal ingredients, including 5-hydroxymethylfurfural. In the present study, an efficient method based on high-speed counter-current chromatography was established for the preparation of 5-hydroxymethylfurfural from Schisandra chinensis. Petroleum ether-ethyl acetate-methanol-water (2:5:2:5, v/v) was selected as the solvent system for high-speed counter-current chromatography. In order to improve the yield of single separation, the sample size was continuously optimized and improved. The results showed that 1,250 mg was the most suitable sample size, and 41 mg of the target compound with 97% purity was obtained in a single run. To further improve the yield, consecutive high-speed counter-current chromatography was introduced and compared with the results of a high-speed counter-current chromatography single run. The results showed that although the purity was reduced to 92%, 430 mg of the target compound was obtained from 12.5 g of ethanol extract within 670 min after 10 consecutive injections. This indicated that consecutive separation not only increased the yield of the target compound, but also saved the separation time and greatly improved the separation efficiency of high-speed counter-current chromatography.

Phosphorus vacancy-engineered Ce-doped CoP nanosheets for the electrocatalytic oxidation of 5-hydroxymethylfurfural.

The electrooxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furanedioic acid (FDCA) has received increasing attention. To achieve satisfactory electrooxidation of HMF, the development of an efficient electrocatalyst is particularly critical. Herein, porous Ce-CoP nanosheets integrating Ce doping and P vacancies are designed through a deep eutectic solvent approach, and they allow the excellent electrocatalytic oxidation of HMF to FDCA in 1 M KOH electrolyte with 100% HMF conversion, 98% FDCA yield, and a faradaic efficiency of 96.4% at low potential.

Low-temperature hydrothermal liquefaction of pomelo peel for production of 5-hydroxymethylfurfural-rich bio-oil using ionic liquid loaded ZSM-5.

Ionic liquid loaded ZSM-5 with high stability and catalytic performance was used for hydrothermal liquefaction (HTL) of pomelo peel for the first time. Bio-oil obtained at 200 °C had the highest yield (29.21 wt%) and high heating value (21.41 MJ/kg), with main constituents of 5-hydroxymethylfurfural (5-HMF, 50.10%), 3-Pyridinol (19.8%) and pentanoic acid (5.35%). The higher 5-hydroxymethylfurfural yield obtained using ionic liquid loaded ZSM-5 was further compared to other studies (0-50%). In comparison to high-temperature HTL, catalytic HTL with ionic liquid loaded ZSM-5 led to lower activation energy requirements (31.93 kJ·mol-1) for the conversion of glucose into 5-HMF. Additionally, the catalysts showed excellent recyclability, with 19.68 wt% of bio-oil containing 59.6% of light oil obtained after 5 cycles. Hence, this study presents a novel approach for the catalytic conversion of lignocellulosic biomass into 5-HMF-rich bio-oil for energy and green chemistry applications.

Reductive Amination of 5-Hydroxymethylfurfural to 2,5-Bis(aminomethyl)furan over Alumina-Supported Ni-Based Catalytic Systems.

Mono- and bimetallic Ni-based catalysts were prepared by screening 6 supports and 14 secondary metals for reductive amination of 5-hydroxymethylfurfural (5-HMF) into 2,5-bis(aminomethyl)furan (BAMF), among which γ-Al2 O3 and Mn were the best candidates. By further optimization of the reaction conditions at 0.4 g catalyst loading for 0.5 g substrate of 5-HMF and 160 °C of reaction temperature, 10Ni/γ-Al2 O3 and 10NiMn(4 : 1)/γ-Al2 O3 achieved the highest BAMF yields of 86.3 and 82.1 %, respectively. Although the BAMF yield values were comparable with that over Raney Ni, the turnover frequencies based on the initial BAMF yield and unit weight of Ni for 10NiMn(4 : 1)/γ-Al2 O3 , 10Ni/γ-Al2 O3 , and Raney Ni were calculated as 0.41, 0.09, and 0.04 h-1 , respectively. X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy showed that the existence of MnOx well dispersed on the γ-Al2 O3 support and its electron transfer effect with Ni particles on the surface of the support contributed to the high efficiency and better recyclability for the five-time reused 10NiMn(4 : 1)/γ-Al2 O3 catalyst.

Effect of acidity regulators on acrylamide and 5-hydroxymethylfurfural formation in French fries: The dual role of pH and acid radical ion.

The influence of acidity regulators and buffers on the formation of acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) in French fries and the underlying mechanism were evaluated. Prior to frying, the potato strips were dipped in the corresponding acidity regulator solutions or buffers for 30 min at room temperature. The results showed that acids inhibited AA formation, but increased 5-HMF levels. The AA level decreased and 5-HMF level increased with decreasing pH of potato strips. Interestingly, increasing concentration of acid radical ions resulted in AA increase and 5-HMF decrease, which was opposite to the acidification effect of citric acid and acetic acid. Both pH and acid radical ion were important factors for AA and 5-HMF formation. Moreover, acidity regulators might impact AA formation by acting on the generation of methylglyoxal (MGO) and glyoxal (GO) and impact 5-HMF formation by acting on the generation of 3-deoxyglucosone (3-DG).

Dose- and Sex-Dependent Changes in Hemoglobin Oxygen Affinity by the Micronutrient 5-Hydroxymethylfurfural and α-Ketoglutaric Acid.

5-Hydroxymethylfurfural (5-HMF) is known to increase hemoglobin oxygen affinity (Hb-O2 affinity) and to induce a left shift of the oxygen dissociation curve (ODC). It is under investigation as a therapeutic agent in sickle cell anemia and in conditions where pulmonary oxygen uptake is deteriorated or limited (e.g., various clinical conditions or altitude exposure). The combination of 5-HMF and α-ketoglutaric acid (αKG) is commercially available as a nutritional supplement. To further elucidate dose effects, ODCs were measured in vitro in venous whole blood samples of 20 healthy volunteers (10 female and 10 male) after the addition of three different doses of 5-HMF, αKG and the combination of both. Linear regression analysis revealed a strong dose-dependent increase in Hb-O2 affinity for 5-HMF (R2 = 0.887; p < 0.001) and the commercially available combination with αKG (R2 = 0.882; p < 0.001). αKG alone increased Hb-O2 affinity as well but to a lower extent. Both the combination (5-HMF + αKG) and 5-HMF alone exerted different P50 and Hill coefficient responses overall and between sexes, with more pronounced effects in females. With increasing Hb-O2 affinity, the sigmoidal shape of the ODC was better preserved by the combination of 5-HMF and αKG than by 5-HMF alone. Concerning the therapeutic effects of 5-HMF, this study emphasizes the importance of adequate dosing in various physiological and clinical conditions, where a left-shifted ODC might be beneficial. By preserving the sigmoidal shape of the ODC, the combination of 5-HMF and αKG at low (both sexes) and medium (males only) doses might be able to better maintain efficient oxygen transport, particularly by mitigating potentially deteriorated oxygen unloading in the tissue. However, expanding knowledge on the interaction between 5-HMF and Hb-O2 affinity in vitro necessitates further investigations in vivo to additionally assess pharmacokinetic mechanisms.

Recent advances in (chemo)enzymatic cascades for upgrading bio-based resources.

Developing (chemo)enzymatic cascades is very attractive for green synthesis, because they streamline multistep synthetic processes. In this Feature Article, we have summarized the recent advances in in vitro or whole-cell cascade reactions with a focus on the use of renewable bio-based resources as starting materials. This includes the synthesis of rare sugars (such as ketoses, L-ribulose, D-tagatose, myo-inositol or aminosugars) from readily available carbohydrate sources (cellulose, hemi-cellulose, starch), in vitro enzyme pathways to convert glucose to various biochemicals, cascades to convert 5-hydroxymethylfurfural and furfural obtained from lignin or xylose into novel precursors for polymer synthesis, the syntheses of phenolic compounds, cascade syntheses of aliphatic and highly reduced chemicals from plant oils and fatty acids, upgrading of glycerol or ethanol as well as cascades to transform natural L-amino acids into high-value (chiral) compounds. In several examples these processes have demonstrated their efficiency with respect to high space-time yields and low E-factors enabling mature green chemistry processes. Also, the strengths and limitations are discussed and an outlook is provided for improving the existing and developing new cascades.

Reduction of 3-Deoxyglucosone by Epigallocatechin Gallate Results Partially from an Addition Reaction: The Possible Mechanism of Decreased 5-Hydroxymethylfurfural in Epigallocatechin Gallate-Treated Black Garlic.

5-Hydroxymethylfurfural (5-HMF) is a harmful substance generated during the processing of black garlic. Our previous research demonstrated that impregnation of black garlic with epigallocatechin gallate (EGCG) could reduce the formation of 5-HMF. However, there is still a lack of relevant research on the mechanism and structural identification of EGCG inhibiting the production of 5-HMF. In this study, an intermediate product of 5-HMF, 3-deoxyglucosone (3-DG), was found to be decreased in black garlic during the aging process, and impregnation with EGCG for 24 h further reduced the formation of 3-DG by approximately 60% in black garlic compared with that in the untreated control. The aging-mimicking reaction system of 3-DG + EGCG was employed to determine whether the reduction of 3-DG was the underlying mechanism of decreased 5-HMF formation in EGCG-treated black garlic. The results showed that EGCG accelerated the decrease of 3-DG and further attenuated 5-HMF formation, which may be caused by an additional reaction with 3-DG, as evidenced by LC-MS/MS analysis. In conclusion, this study provides new insights regarding the role of EGCG in blocking 5-HMF formation.

Effects of Sprouting and Fermentation on Free Asparagine and Reducing Sugars in Wheat, Einkorn, Oat, Rye, Barley, and Buckwheat and on Acrylamide and 5-Hydroxymethylfurfural Formation during Heating.

Usage of sprouted grains is an increasing trend in thermally processed foods. Sprouting alters the composition of sugars and amino acids, which are Maillard reaction precursors. Free asparagine, total free amino acids, and sugars were monitored during sprouting and yeast and sourdough fermentations. Acrylamide and 5-hydroxymethylfurfural (HMF) were analyzed in heated samples. The asparagine concentration decreased up to 40% after 24-36 h of sprouting, except for buckwheat, and then increased to the initial concentration after 48 h and several folds after 72 h. The increased amount of reducing sugars after sprouting caused higher acrylamide and HMF formation even if the asparagine concentration was lower. Acrylamide and HMF formation decreased after fermentation of sprouted wholemeal because sugars and asparagine were consumed by yeast. A pH drop of 3 units by sourdough fermentation decreased acrylamide formation but increased HMF formation. Results indicated that sprouted cereal products should be produced under controlled conditions to be used in heated foods.

Effect of various roasting, extraction and drinking conditions on furan and 5-hydroxymethylfurfural levels in coffee.

Furan and 5-hydroxymethylfurfural (5-HMF) were quantified in 108 coffee models prepared considering the species/origin of the coffee beans, roasting temperature/time, mesh size used to sieve the ground coffee beans, type of extraction water and extraction method. The effect of drinking conditions, such as adding sugar or cream, on furan and 5-HMF levels, was also studied. The range of furan and 5-HMF in coffee samples were 5-362 ppb and 51-1143 ppm, respectively. Furan levels were increased by 198-560% with increasing roasting temperature/time and by 106-399% in cold-brew extracts compared with espresso extracts. Among the mesh sizes used, 500 µm with espresso extraction, and 710 µm with cold-brew extraction led to maximal furan levels. 5-HMF concentration was highest in Robusta coffee and espresso extracts, and decreased by 17-76% with increasing roasting temperature/time. In a drinking condition study, furan level was remained unchanged, even when sugar or cream were added.

Modulation of Hb-O2 affinity to improve hypoxemia in COVID-19 patients.

This opinion paper aims at discussing the potential impact of modulating the Hb-O2 affinity by the nutritional supplement 5-HMF on patients affected by COVID-19. The paper describes the critical role of the oxygen affinity in hypoxemic COVID-19 patients and the potential positive effect of 5-HMF, a compound shown to increase the Hb-O2 affinity.

A novel UHPLC method for determining the degree of coffee roasting by analysis of furans.

The aim of this study was to develop a multi-analyte UHPLC method for furans and to apply it to commercial coffee samples as well as commercial roasting trials. Furans, as rising time-temperature indicators (TTIs), promised to be an alternative to unsatisfactory roasting temperature measurements. Consequently, a UHPLC-UV method for the determination of 5-hydroxymethyl-2-furfural (HMF), 5-hydroxymethyl-2-furoic acid (HMFA), 2-furfural (F), 5-methylfurfural (MF), 2-furyl methyl ketone (FMC), 2-furoic acid (FA), and for 3-caffeoylquinic acid (3-CQA) was developed and validated. Commercial roasted coffee beans contained 77.7-322 mg/kg HMF, 73.3-158 mg/kg HMFA, 109-200 mg/kg 2-F, 157-209 mg/kg MF, 12.3-32.8 mg/kg FMC, and 137-205 mg/kg FA. Roasting trial samples showed strong rising HMF contents (max.: Arabica: 769 mg/kg, Robusta: 364 mg/kg) followed by a distinct decline. Only MF and FA appeared as steady rising TTIs in the roasting process in Arabica and Robusta beans. 3-CQA fitted well as a decreasing TTI as expected.

5-Hydroxymethylfurfural and α-ketoglutaric acid supplementation increases oxygen saturation during prolonged exercise in normobaric hypoxia.

This double-blinded, randomized and placebo-controlled, crossover study investigated whether α-ketoglutaric-acid (α-KG) and 5-hydroxymethylfurfural (5-HMF) supplementation improves exercise performance in hypoxia and affects physiological responses during the exercise task. Eight moderately trained male participants (age: 25.3 ± 2.0 y, VO2max: 48.0 ± 8.3 ml/min/kg) performed an incremental exercise test to exhaustion in normoxia and two 2-hour cycle time trial (TT) tests in hypoxia (3,500 m) each separated by 1-week. Prior to the TT, participants supplemented with either α-KG and 5-HMF or placebo (random order). Supplementation did not improve TT performance at altitude and did not affect heart rate, effort perception and oxidative stress levels (p > 0.05). Oxygen saturation (SpO2) was enhanced during the α-KG and 5-HMF supplementation trial (79.5 ± 3.3 vs. 78.2 ± 3.7%, p = 0.026). Even though TT performance was unaffected, the enhanced SpO2 - possibly originated from changed O2-affinity - deserves further consideration as the exercise performance decline at altitude is strongly linked to the SpO2 decline. The inclusion of moderately fit participants, not specifically cycle trained, might have prevented any visible performance enhancement.