Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men

Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type 2 diabetes. Our study included 8749 Finnish men without diabetes at baseline recruited from the Metabolic Syndrome in Men (METSIM) cohort. We used a questionnaire to measure leisure-time PA. Metabolites were measured in 7271 men as a part of Metabolon’s untargeted Discovery HD4 platform using ultrahigh-performance liquid chromatography–tandem mass spectrometry. We found 198 metabolites significantly associated with PA. Several of these metabolites were novel including especially steroids, amino acids, imidazoles, carboxylic acids, and hydroxy acids. Increased PA was significantly associated with high levels of choline plasmalogens, lysophosphatidylcholines, polyunsaturated fatty acids, carotenoids, long chain acylcarnitines, imidazoles, bilirubins, aryl sulfates, hydroxy acids, indolepropionate, and indolelactate. Several of these metabolites have been previously associated with a decreased risk of type 2 diabetes and with a healthy diet. Our population-based study shows that the metabolite signature of increased PA includes multiple metabolic pathways and is associated with better adherence to a healthy lifestyle.

The impact of bariatric surgery on serum tryptophan–kynurenine pathway metabolites

This study aims to explore the immediate effects of bariatric surgery on serum tryptophan–kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).

LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study

Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat blood, and reported their pharmacokinetic parameters. The chromatographic separation and detection of analytes were achieved within 4 min on ZORBAX SB-C8 (3.5 μm, 2.1 × 150 mm) column with gradient elution, and the flow rate was 0.25 mL/min. Simple protein precipitation was successfully applied for sample pretreatment. The HCQ displays a good linearity in the range of 2.0–5000.0 ng/mL, and the three metabolites also show good linearity ranging from 1.0 to 2500.0 ng/mL, with all correlation coefficients (R2) better than 0.98. In conclusion, this rapid, sensitive method was successfully developed, validated, and then applied to a pharmacokinetic study of HCQ in rat model in high dose. The results of the pharmacokinetic study presented an average half-life time 21.14 ± 10.31 h (mean ± SD) of HCQ, which is much shorter in human compared to that in mice. For the three metabolites, longer half-life times (approximately 100 h) were shown in rat.

In Vitro Anti-Diabetic Activities and UHPLC-ESI-MS/MS Profile of Muntingia calabura Leaves Extract

Anti-diabetic compounds from natural sources are now being preferred to prevent or treat diabetes due to adverse effects of synthetic drugs. The decoction of Muntingia calabura leaves was traditionally consumed for diabetes treatment. However, there has not been any published data currently available on the processing effects on this plant’s biological activity and phytochemical profile. Therefore, this study aims to evaluate the effect of three drying methods (freeze-drying (FD), air-drying (AD), and oven-drying (OD)) and ethanol:water ratios (0, 50, and 100%) on in vitro anti-diabetic activities of M. calabura leaves. In addition, an ultrahigh-performance-liquid chromatography–electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was used to characterize the metabolites in the active extract. The FD M. calabura leaves, extracted with 50% ethanol, is the most active extract that exhibits a high α-glucosidase and α-amylase inhibitory activities with IC50 values of 0.46 ± 0.05 and 26.39 ± 3.93 µg/mL, respectively. Sixty-one compounds were tentatively identified by using UHPLC-ESI-MS/MS from the most active extract. Quantitative analysis, by using UHPLC, revealed that geniposide, daidzein, quercitrin, 6-hydroxyflavanone, kaempferol, and formononetin were predominant compounds identified from the active extract. The results have laid down preliminary steps toward developing M. calabura leaves extract as a potential source of bioactive compounds for diabetic treatment.

Evaluation of the Effects of Processing Technique on Chemical Components in Raphani Semen by HPLC and UPLC-Q-TOF-MS

In this study, the effects of different processing techniques on the chemical components of Raphani Semen (RS) were evaluated. An established high-performance liquid chromatography (HPLC) method was adopted for the simultaneous determination of glucoraphanin, sinapine thiocyanate, raphanin, and erucic acid in the fried products of Raphani Semen to evaluate the chemical changes during frying processing as well as optimize the best frying technology of Raphani Semen. Then, the chemical components in the fried Raphani Semen were identified by ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A total of 54 compounds in processed Raphani Semen were identified by UPLC-Q-TOF-MS. The results showed that the content of glucoraphanin and sinapine thiocyanate was the highest in the fried products at 130°C for 10 min, and the effect of “Enzyme Killing and Glycosides Preserving” was the best. Therefore, this condition was chosen as the best frying technology of Raphani Semen. This study provided a more scientific basis for evaluation of the quality of Raphani Semen fried products and optimization of the frying technology of Raphani Semen.

Water Extract of Fritillariae thunbergii Bulbus Inhibits RANKL-Mediated Osteoclastogenesis and Ovariectomy-Induced Trabecular Bone Loss

Fritillariae thunbergii bulbus has been widely used to treat symptoms of coughs and airway congestion in the chest due to pathological colds and damp phlegm in traditional Chinese medicine. Despite its long history of traditional use, its pharmacological activities on osteoclastogenesis and osteoporosis have not been evaluated. This study investigated the effects of the water extract of Fritillariae thunbergii bulbus (WEFT) on osteoclast differentiation in bone marrow-derived macrophage cells and on ovariectomy (OVX)-induced osteoporosis in mice. We found that WEFT significantly inhibited osteoclastogenesis by downregulating the receptor activator of the NF-κB ligand (RANKL) signaling-induced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. In an OVX-induced osteoporosis model, WEFT significantly prevented the OVX-induced trabecular loss of femurs, accompanied by a reduction in fat accumulation in the bone marrow and liver. In addition, WEFT significantly prevented weight gain and gonadal fat gain without recovering uterine atrophy. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, seven alkaloids (peimisine glucoside, yibeissine, peiminoside, sipeimine-glucoside, peimisine, peimine, and peiminine) were identified in WEFT. The results of this study suggest that WEFT can be a potential pharmacological candidate to reduce menopausal osteoporosis and menopause-related symptoms, such as fat accumulation.

Identification of Chemical Components of Qi-Fu-Yin and Its Prototype Components and Metabolites in Rat Plasma and Cerebrospinal Fluid via UPLC-Q-TOF-MS

Qi-Fu-Yin, a traditional Chinese medicine formula, has been used to treat Alzheimer’s disease (AD, a neurodegenerative disorder) in clinical setting. In this study, the chemical components of Qi-Fu-Yin and its prototype components and metabolites in rat plasma and cerebrospinal fluid, after oral administration, were preliminarily characterized via ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). A total of 180 compounds, including saponins, flavonoids, organic acids, sucrose esters, oligosaccharide esters, phthalides, phenylethanoid glycosides, alkaloids, xanthones, terpene lactones, ionones, and iridoid glycoside, were tentatively characterized. For the first time, 51 prototypical components and 26 metabolites, including saponins, phthalides, flavonoids, sucrose esters, organic acids, alkaloids, ionones, terpene lactones, iridoid glycoside, and their derivatives, have been tentatively identified in the plasma. Furthermore, 10 prototypical components (including butylidenephthalide, butylphthalide, 20(S)-ginsenoside Rh1, 20(R)-ginsenoside Rh1, and zingibroside R1) and 6 metabolites were preliminarily characterized in cerebrospinal fluid. These results were beneficial to the discovery of the active components of Qi-Fu-Yin anti-AD.

Supervised Statistical Learning Prediction of Soybean Varieties and Cultivation Sites Using Rapid UPLC-MS Separation, Method Validation, and Targeted Metabolomic Analysis of 31 Phenolic Compounds in the Leaves

Soybean (Glycine max; SB) leaf (SL) is an abundant non-conventional edible resource that possesses value-adding bioactive compounds. We predicted the attributes of SB based on the metabolomes of an SL using targeted metabolomics. The SB was planted in two cities, and SLs were regularly obtained from the SB plant. Nine flavonol glycosides were purified from SLs, and a validated simultaneous quantification method was used to establish rapid separation by ultrahigh-performance liquid chromatography-mass detection. Changes in 31 targeted compounds were monitored, and the compounds were discriminated by various supervised machine learning (ML) models. Isoflavones, quercetin derivatives, and flavonol derivatives were discriminators for cultivation days, varieties, and cultivation sites, respectively, using the combined criteria of supervised ML models. The neural model exhibited higher prediction power of the factors with high fitness and low misclassification rates while other models showed lower. We propose that a set of phytochemicals of SL is a useful predictor for discriminating characteristics of edible plants.