Glyoxal Caging of Nucleoside Antivirals toward Self-Activating, Extended-Release Prodrugs.

Nucleoside antivirals are a leading class of compounds prescribed as a first-line treatment for viral infections. However, inherent limitations such as low solubility and circulation lifetime can necessitate multi-intraday dosing. Here, we deploy the 1,2-dialdehyde glyoxal to generate antiviral nucleoside prodrugs with enhanced pharmacokinetic properties and extended-release activity to combat poor patient adherence. The near-quantitative reaction of glyoxal with acyclovir (ACV) drastically improves ACV solubility and enables subsequent drug release with a half-life of 1.9 h under physiological conditions. Further, glyoxal caging thermoreversibly disrupts ACV activity against HIV-1 reverse transcription in vitro and HSV-1 pathology in cellulo. Finally, the amenability of a panel of nucleoside reverse transcriptase inhibitors to glyoxal caging showcases the potential of this highly versatile method for achieving timed-release activation of a clinically important class of antiviral therapeutics.

Brewer's Spent Grain-Cellulose-Coated Copper Electrode-Based Extended Gate Field-Effect Transistor for Nonenzymatic Glucose Detection toward Diagnosis of Diabetes Mellitus.

The demand for environmentally friendly, reliable, and cost-effective electrodes for glucose sensor technology has become a major research area in the paradigm shift toward green electronics. In this regard, cellulose has emerged as a promising flexible biopolymer solution with unique properties such as biocompatibility, biodegradability, nontoxicity, renewability, and sustainability. Because of their large surface area and porous structure, fibrous cellulose substrates quickly adsorb and disperse analytes at detection sites. This work focuses on utilizing glyoxal-treated cellulose (derived from brewer's spent grain (BSG)) for the fabrication of extended gate field-effect transistor (EGFET)-based glucose sensors. This investigation extends to the utilization of BSG-cellulose for glucose detection in biomimicking electrolytes (phosphate buffer saline) to facilitate glucose detection in human blood samples. The fabricated electrode demonstrates a linear range of glucose detection from 1 to 13.5 mM with a Langmuir adsorption coefficient (K) of 0.102. Also, its selectivity toward glucose over interfering molecules such as sucrose, fructose, ascorbic acid, and uric acid under physiological conditions has been demonstrated. This cellulose-based EGFET electrode exhibits a sensitivity of 6.5 µA mM-1 cm-2 with a limit of detection (LOD) of 0.135 mM. Computational studies by density functional theory calculations confirmed the higher binding affinity of glucose molecules with glyoxal-modified cellulose (-0.95 eV) than with pristine cellulose (-0.46 eV). Here, the novelty lies in the fabrication of electrodes with biodegradable catalysts and their integration into the EGFET configuration.

Balancing Maillard reaction products formation and antioxidant activities for improved sensory quality and health benefit properties of pan baked buns.

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.

Capture of single or multiple reactive carbonyl species by mangiferin under high temperatures.

Reactive carbonyl species (RCS), including acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO), are typically generated in food processing and accumulate in the body for ages, triggering various chronic diseases. Here, we investigated the capture capability and reaction pathways of mangiferin one-to-one and one-to-many on RCS in high temperatures using UPLC-MS/MS. We found that mangiferin can capture ACR/MGO/GO to form their adducts, yet, the ability to capture RCS is arranged in different orders, with ACR > MGO > GO for a single RCS and MGO > ACR > GO for multiple RCS. After synthesizing and identifying the structures of the ACR- and MGO-adducts of MGF, our results indicated that MGF-ACR-MGO produced in the multiple-RCS-MGF system was formed by capturing MGO through MGF-ACR rather than through MGF-MGO capturing ACR, which resulting in higher inhibitory activity of MGF against MGO than against ACR. Then, the capture ability and path of MGF on RCS were verified in the coffee-leaves tea and cake.

Qualitative and Quantitative Profiling of Fructose Degradation Products Revealed the Formation of Thirteen Reactive Carbonyl Compounds and Higher Reactivity Compared to Glucose.

Fructose occurs in foods and as a metabolite in vivo. It can be degraded, leading to the formation of reactive carbonyl compounds, which may influence food properties and have an impact on health. The present study performed an in-depth qualitative and quantitative profiling of fructose degradation products. Thus, the α-dicarbonyl compounds 3-deoxyglucosone, glucosone, methylglyoxal, glyoxal, hydroxypyruvaldehyde, threosone, 3-deoxythreosone, and 1-desoxypentosone and the monocarbonyl compounds formaldehyde, acetaldehyde, glycolaldehyde, glyceraldehyde, and dihydroxyacetone were detected in fructose solutions incubated at 37 °C. Quantitative profiling after 7 days revealed 4.6-271.6-fold higher yields of all degradation products from fructose compared to glucose. Except for 3-deoxyglucosone, the product formation appeared to be metal dependent, indicating oxidative pathways. CaCl2 and MgCl2 partially reduced fructose degradation. Due to its high reactivity compared to glucose, particularly toward metal-catalyzed pathways, fructose may be a strong contributor to sugar degradation and Maillard reaction in foods and in vivo.

Selectively lighting up glyoxal in living cells using an o-phenylenediamine fused hemicyanine.

Glyoxal (GL) is a reactive α-dicarbonyl compound generated from glycated proteins in the Maillard reaction. It has attracted particular attention over the past few years because of its possible clinical significance in chronic and age-related diseases. In this work, a reaction-based red emission fluorescent probe GL1 has been synthesized successfully by grafting an alkyl group onto an amino group to regulate its selectivity for GL. Under physiological conditions, the fluorescence intensity of GL1 at 640 nm obviously increased with the increase of GL concentration, and it exhibited high selectivity for GL over other reactive carbonyl compounds, as well as a lower detection limit (0.021 µM) and a larger Stokes shift (112 nm). At the same time, GL1 can selectively accumulate in mitochondria and can be used to detect exogenous and endogenous GL in living cells with low cytotoxicity.

The reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes.

Complications of diabetes are often attributed to glucose and reactive dicarbonyl metabolites derived from glycolysis or gluconeogenesis, such as methylglyoxal. However, in the CNS, neurons and endothelial cells use lactate as energy source in addition to glucose, which does not lead to the formation of methylglyoxal and has previously been considered a safer route of energy consumption than glycolysis. Nevertheless, neurons and endothelial cells are hotspots for the cellular pathology underlying neurological complications in diabetes, suggesting a cause that is distinct from other diabetes complications and independent of methylglyoxal. Here, we show that in clinical and experimental diabetes plasma concentrations of dimethylglyoxal are increased. In a mouse model of diabetes, ilvb acetolactate-synthase-like (ILVBL, HACL2) is the enzyme involved in formation of increased amounts of dimethylglyoxal from lactate-derived pyruvate. Dimethylglyoxal reacts with lysine residues, forms Nε-3-hydroxy-2-butanonelysine (HBL) as an adduct, induces oxidative stress more strongly than other dicarbonyls, causes blood-brain barrier disruption, and can mimic mild cognitive impairment in experimental diabetes. These data suggest dimethylglyoxal formation as a pathway leading to neurological complications in diabetes that is distinct from other complications. Importantly, dimethylglyoxal formation can be reduced using genetic, pharmacological and dietary interventions, offering new strategies for preventing CNS dysfunction in diabetes.

The kinetic study of 2-acetyl-1-pyrroline accumulation in the model system: An insight into enhancing rice flavor through the Maillard reaction.

Controlling the Maillard reaction may affect the generation of 2-acetyl-1-pyrroline, the key aroma compound in rice. In this study, the kinetics of 2-acetyl-1-pyrroline accumulation in the glucose/proline model system was comprehensively investigated and extra methylglyoxal or glyoxal was added to enhance 2-acetyl-1-pyrroline concentrations during rice cooking. Using the multi-response kinetic modeling to derive kinetic parameters, the formation of glyoxal, as the reactive intermediate, was rate-determining for the overall generation rate of 2-acetyl-1-pyrroline. Besides, although 2-acetyl-1-pyrroline generation was easier to occur with lower activation energy, much higher depletion rates of 2-acetyl-1-pyrrroline at 120 °C and 140 °C led to maximal 2-acetyl-1-pyrroline accumulation at the lower temperature of 100 °C. Furthermore, the inclusion of 0.05 µmol/kg additional methylglyoxal in cooked rice significantly enhanced 2-acetyl-1-pyrroline generation. The work suggested that the development of rice products with superior flavor quality may be achieved by the slight accumulation of intermediates prior to thermal processing.

Evaluation of potentially harmful Maillard reaction products in different types of commercial formulae.

Pasteurisation and spray drying are critical steps to ensure the safety and shelf-life of formulae, but these treatments also induce formation of some potentially harmful Maillard reaction products. In this study, the occurrence of potentially harmful Maillard reaction products and proximate compositions in different commercial formulae were analysed. Our results showed that infant formulae had significantly higher concentrations of furosine, Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) than follow-on/toddler formula. Specialty formulae had higher concentrations of glyoxal and CML than other types of formulae. Correlation analysis indicated that concentrations of 5-hydroxymethylfurfural, 3-deoxyglucosone, CML and CEL were closely related to fat contents. These results provided insight into concentrations of potentially harmful Maillard reaction products in different types of formulae and provide a theoretical basis for further optimisation of processing.

Development of environmentally friendly glyoxal-based adhesives with outstanding water repellency utilizing wheat gluten protein.

To reduce the release of volatile organic compounds (VOCs) from formaldehyde-based adhesives at the source, the use of low-toxicity and biodegradable glyoxal instead of formaldehyde for the preparation of novel urea-glyoxal resins is a simple and promising strategy. The limited water resistance and adhesive strength of the new urea-glyoxal resins (UG) restrict their extensive application. This study prepared a high-performance, water-resistant WP-UG wood adhesive by combining UG prepolymer with wheat gluten protein (WP). FTIR, XRD, and XPS confirmed the existence of a chemical reaction between the two components, and thermal analysis showed that WP-UG plywood had better thermal stability. Evaluation of the gluing properties revealed that the dry and wet strengths of WP-UG adhesive bonded plywood reached 1.39 and 0.87 MPa, respectively, which were significantly higher than those of UG resin by 35 % and 314 %. The bond strength increased from 0 to 0.89 MPa after immersion in water at 63 °C for 3 h. The results indicated that the introduction of WP promoted the formation of a more complex and tightly packed crosslinking network and developed a glyoxal-based adhesive with high bond strength and water resistance. This study provides a new green pathway for novel urea-formaldehyde binders to replace harmful formaldehyde-based binders, which helps to increase their potential application value in the wood industry.

Theanine Capture of Reactive Carbonyl Species in Humans after Consuming Theanine Capsules or Green Tea.

Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and age-related diseases. Here, we explored a new RCS inhibitor (theanine, THE) and investigated its capture capacity on RCS in vivo by human experiments. After proving that theanine could efficiently capture ACR instead of MGO/GO by forming adducts under simulated physiological conditions, we further detected the ACR/MGO/GO adducts of theanine in the human urine samples after consumption of theanine capsules (200 and 400 mg) or green tea (4 cups, containing 200 mg of theanine) by using ultraperformance liquid chromatography-time-of-flight-high-resolution mass spectrometry. Quantitative assays revealed that THE-ACR, THE-2ACR-1, THE-MGO, and THE-GO were formed in a dose-dependent manner in the theanine capsule groups; the maximum value of the adducts of theanine was also tested. Furthermore, besides the RCS adducts of theanine, the RCS adducts of catechins could also be detected in the drinking tea group. Whereas, metabolite profile analysis showed that theanine could better capture RCS produced in the renal metabolic pathway than catechins. Our findings indicated that theanine could reduce RCS in the body in two ways: as a pure component or contained in tea leaves.

Glyoxal and methylglyoxal formation in chocolate and their bioaccessibility.

The objective of this study was to assess the effects of simulated digestion on the formation of α-dicarbonyl compounds (α-DCs) in chocolates. For that purpose, the concentrations of glyoxal and methylglyoxal in chocolates were determined through High-Performance Liquid Chromatography (HPLC) analysis before and after in vitro digestion. The initial concentrations ranged from 0.0 and 228.2 µg/100 g, and 0.0 and 555.1 for glyoxal and methylglyoxal, respectively. Following digestion, there was a significant increase in both glyoxal and methylglyoxal levels, reaching up to 1804 % and 859 %, respectively. The findings indicate that digestive system conditions facilitate the formation of advanced glycation end product (AGE) precursors. Also, glyoxal and methylglyoxal levels were found to be low in chocolate samples containing dark chocolate. In contrast, they were found to be high in samples containing hazelnuts, almonds, pistache, and milk. Further studies should focus on α-DCs formation under digestive system conditions, including the colon, to determine the effects of gut microbiota.

Evaluation of changes in carbonyl stress markers with treatment in male patients with bipolar disorder manic episode: A controlled study.

BACKGROUND: Carbonyl stress, a metabolic state characterized by elevated production of reactive carbonyl compounds (RCCs), is closely related to oxidative stress and has been implicated in various diseases. This study aims to investigate carbonyl stress parameters in drug-free bipolar disorder (BD) patients compared to healthy controls, explore their relationship with clinical features, and assess the effect of treatment on these parameters. METHODS: Patients with a primary diagnosis of a manic episode of BD and healthy controls were recruited. Exclusion criteria included intellectual disability, presence of neurological diseases, chronic medical conditions such as diabetes mellitus and metabolic syndrome, and clinical signs of inflammation. Levels of serum carbonyl stress parameters were determined using high-performance liquid chromatography. RESULTS: Levels of glyoxal (GO) and methylglyoxal (MGO) did not differ between pre- and post-treatment patients, but malondialdehyde (MDA) levels decreased significantly post-treatment. Pre-treatment MGO and MDA levels were higher in patients compared to controls, and these differences persisted post-treatment. After adjusting for BMI and waist circumference, only MDA levels remained significantly higher in patients compared to controls. LIMITATIONS: The study's limitations include the exclusion of female patients, which precluded any assessment of potential gender differences, and the lack of analysis of the effect of specific mood stabilizers or antipsychotic drugs. CONCLUSIONS: This study is the first to focus on carbonyl stress markers in BD, specifically GO, MGO, and MDA. MDA levels remained significantly higher in patients, suggesting a potential role in BD pathophysiology. MGO levels were influenced by metabolic parameters, indicating a potential link to neurotoxicity in BD. Further research with larger cohorts is needed to better understand the role of RCCs in BD and their potential as therapeutic targets.

Glyoxal-methyl-ethylene sulfonic acid fixative enhances the fixation of cytoskeletal structures for Förster resonance energy transfer measurements.

Förster resonance energy transfer (FRET) serves as a tool for measuring protein-protein interactions using various sensor molecules. The tension sensor module relies on FRET technology. In our study, this module was inserted within the actinin molecule to measure the surface tension of the cells. Given that the decay curve of FRET efficiency correlates with surface tension increase, precise and accurate efficiency measurement becomes crucial. Among the methods of FRET measurements, FRET efficiency remains the most accurate if sample fixation is successful. However, when cells were fixed with 4% paraformaldehyde (PFA), the actinin-FRET sensor diffused across the cytoplasm; this prompted us to explore fixation method enhancements. Glyoxal fixative has been reported to improve cytoskeletal morphologies compared to PFA. However, it was not known whether glyoxal fits FRET measurements. Glyoxal necessitates an acetic acid solution for fixation; however, acidic conditions could compromise fluorescence stability. We observed that the pH working range of glyoxal fixative aligns closely with MES (methyl-ethylene sulfonic acid) Good's buffer. Initially, we switched the acidic solution for MES buffer and optimized the fixation procedure for in vitro and in vivo FRET imaging. By comparing FRET measurements on hydrogels with known stiffness to tumor nodules in mouse lung, we estimated in vivo stiffness. The estimated stiffness of cancerous tissue was harder than the reported stiffness of smooth muscle. This discovery shed lights on how cancer cells perceive environmental stiffness during metastasis.

Absorption and intracellular accumulation of food-borne dicarbonyl precursors of advanced glycation end-product in a Caco-2 human cell transwell model.

This study aimed to better understand whether and how the reactive 1,2-dicarbonyl precursors of advanced glycation end products (AGEs), glyoxal (GO) and methylglyoxal (MGO), cross the intestinal barrier by studying their transport in the in vitro Caco-2 transwell system. The results reveal that GO, MGO and Nε-(carboxymethyl)lysine (CML), the latter studied for comparison, are transported across the intestinal cell layer via both active and passive transport and accumulate in the cells, albeit all to a limited extent. Besides, the transport of the dicarbonyl compounds was only partially affected by the presence of amino acids and protein, suggesting that scavenging by a food matrix will not fully prevent their intestinal absorption. Our study provides new insights into the absorption of the two major food-borne dicarbonyl AGE precursors and provides evidence of their potential systemic bioavailability but also of factors limiting their contribution to the overall exposome.

Coffee leaf extract inhibits advanced glycation end products and their precursors: A mechanistic study.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

Formation of Volatile Pyrazinones in Amadori Rearrangement Products and Maillard Reaction Systems and the Major Formation Pathways.

Amadori rearrangement products (ARPs) are gaining more attention for their potential usage in the food flavor industry. Peptide-ARPs have been studied, but pyrazinones that were theoretically found in the Maillard reaction (MR) have not been reported to be formed from small peptide-ARPs. This study found four pyrazinones: 1-methyl-, 1,5-dimethyl-, 1,6-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones in both MR and ARP systems. It was the first time 1-methyl-2(1H)-pyrazinone was reported, along with 1,5-dimethyl- and 1,5,6-trimethyl-2(1H)-pyrazinones being purified and analyzed by nuclear magnetic resonance for the first time. The primary formation routes of the pyrazinones were also proven as the reaction between diglycine and α-dicarbonyls, including glyoxal, methylglyoxal, and diacetyl. The pyrazinones, especially 1,5-dimethyl-2(1H)-pyrazinone, have strong fluorescence intensity, which may be the reason for the increase of fluorescence intensity in MR besides α-dicarbonyls. Cytotoxicity analysis showed that both Gly-/Digly-/Trigly-ARP and the three pyrazinones [1-methyl-, 1,5-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones] showed no prominent cytotoxicity in the HepG2 cell line below 100 µg/mL, further suggesting that ARPs or pyrazinones could be used as flavor additives in the future. Further research should be conducted to investigate pyrazinones in various systems, especially the peptide-ARPs, which are ubiquitous in real food systems.

Investigations of Major α-Dicarbonyl Content in U.S. Honey of Different Geographical Origins.

α-Dicarbonyls are significant degradation products resulting from the Maillard reaction during food processing. Their presence in foods can indicate the extent of heat exposure, processing treatments, and storage conditions. Moreover, they may be useful in providing insights into the potential antibacterial and antioxidant activity of U.S. honey. Despite their importance, the occurrence of α-dicarbonyls in honey produced in the United States has not been extensively studied. This study aims to assess the concentrations of α-dicarbonyls in honey samples from different regions across the United States. The identification and quantification of α-dicarbonyls were conducted using reverse-phase liquid chromatography after derivatization with o-phenylenediamine (OPD) and detected using ultraviolet (UV) and mass spectrometry methods. This study investigated the effects of pH, color, and derivatization reagent on the presence of α-dicarbonyls in honey. The quantification method was validated by estimating the linearity, precision, recovery, method limit of detection, and quantification using known standards for GO, MGO, and 3-DG, respectively. Three major OPD-derivatized α-dicarbonyls including methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), were quantified in all the honey samples. 3-Deoxyglucosone (3-DG) was identified as the predominant α-dicarbonyl in all the U.S. honey samples, with concentrations ranging from 10.80 to 50.24 mg/kg. The total α-dicarbonyl content ranged from 16.81 to 55.74 mg/kg, with the highest concentration measured for Southern California honey. Our results showed no significant correlation between the total α-dicarbonyl content and the measured pH solutions. Similarly, we found that lower amounts of the OPD reagent are optimal for efficient derivatization of MGO, GO, and 3-DG in honey. Our results also indicated that darker types of honey may contain higher α-dicarbonyl content compared with lighter ones. The method validation results yielded excellent recovery rates for 3-DG (82.5%), MGO (75.8%), and GO (67.0%). The method demonstrated high linearity with a limit of detection (LOD) and limit of quantitation (LOQ) ranging from 0.0015 to 0.002 mg/kg and 0.005 to 0.008 mg/kg, respectively. Our results provide insights into the occurrence and concentrations of α-dicarbonyl compounds in U.S. honey varieties, offering valuable information on their quality and susceptibility to thermal processing effects.

Determination of α-Dicarbonyl compounds in traditional Chinese herbal medicines.

α-DCs (α-dicarbonyls) have been proven to be closely related to aging and the onset and development of many chronic diseases. The wide presence of this kind of components in various foods and beverages has been unambiguously determined, but their occurrence in various phytomedicines remains in obscurity. In this study, we established and evaluated an HPLC-UV method and used it to measure the contents of four α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) in 35 Chinese herbs after they have been derivatized with 4-nitro-1,2-phenylenediamine. The results uncover that 3-DG is the major component among the α-DCs, being detectable in all the selected herbs in concentrations ranging from 22.80 µg/g in the seeds of Alpinia katsumadai to 7032.75 µg/g in the fruit of Siraitia grosuenorii. The contents of the other three compounds are much lower than those of 3-DG, with GO being up to 22.65 µg/g, MGO being up to 55.50 µg/g, and DA to 18.75 µg/g, respectively. The data show as well the contents of the total four α-DCs in the herbs are generally in a comparable level to those in various foods, implying that herb medicines may have potential risks on human heath in view of the α-DCs.

Scavenging Glyoxal and Methylglyoxal by Synephrine and Neohesperidin from Flowers of Citrus aurantium L. var. amara Engl. in Mice and Humans.

There is considerable research evidence that α-dicarbonyl compounds, including glyoxal (GO) and methylglyoxal (MGO), are closely related to many chronic diseases. In this work, after comparison of the capture capacity, reaction pathway, and reaction rate of synephrine (SYN) and neohesperidin (NEO) on GO/MGO in vitro, experimental mice were administrated with SYN and NEO alone and in combination. Quantitative data from UHPLC-QQQ-MS/MS revealed that SYN/NEO/HES (hesperetin, the metabolite of NEO) could form the GO/MGO-adducts in mice (except SYN-MGO), and the levels of GO/MGO-adducts in mouse urine and fecal samples were dose-dependent. Moreover, SYN and NEO had a synergistic scavenging effect on GO in vivo by promoting each other to form more GO adducts, while SYN could promote NEO to form more MGO-adducts, although it could not form MGO-adducts. Additionally, human experiments showed that the GO/MGO-adducts of SYN/NEO/HES found in mice were also detected in human urine and fecal samples after drinking flowers of Citrus aurantium L. var. amara Engl. (FCAVA) tea using UHPLC-QTOF-MS/MS. These findings provide a novel strategy to reduce endogenous GO/MGO via the consumption of dietary FCAVA rich in SYN and NEO.