Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis.

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Improving natural products identification through molecular features-oriented precursor ion selection and targeted MS/MS analysis: a case study of Zhi-Ke-Yang-Yin capsule.

Chemical substance identification is an indispensable step in research on therapeutic materials based on traditional Chinese medicine and its formulas. The successful characterization of chemical substances mainly relies on high-quality MS/MS spectra. However, to date, relatively few studies have specifically addressed the issues of improving the acquisition of MS/MS spectra of compounds for characterization. The current auto-MS/MS mode, where the precursor ions are selected depending on their signal intensity, encounters a drawback when the sample contains many overlapping signals, leading to compounds with a lower or much lower abundance missing identification. To solve this problem, a strategy in which molecular features oriented precursor ion selection was followed by targeted MS/MS analysis for structure elucidation was proposed. The precursor ions were selected according to their first and second molecular features, namely m/z and retention time, irrespective of their intensities. By performing targeted MS/MS analysis, the MS/MS spectra of many more compounds of interest can be obtained, leading to an improvement in natural product identification. As an example, the chemical substances in the Zhi-Ke-Yang-Yin extract were analyzed using this strategy, and as a result, 431 ingredients were tentatively characterized, including both known and unknown or new compounds.

A Newly Discovered Phenylethanoid Glycoside from Stevia rebaudiana Bertoni Affects Insulin Secretion in Rat INS-1 Islet ß Cells.

The tea-like beverage Stevia rebaudiana Bertoni (Stevia) is popular in China because it reduces blood glucose and has a sweet taste. In this work, a comprehensive quality assessment of Stevia led to the discovery of five phenylethanoid glycosides, namely steviophethanoside (1), cuchiloside (2), salidroside (3), icariside D (4), and tyrosol (5). Of them, compound 1 is a novel compound. Mass spectrometry and NMR spectroscopy were employed to confirm the absolute configuration. A hydrolytic step with 4 N TFA at 95 °C for 4 h was used to confirm the monosaccharides. In addition, Discovery Studio 4.0 was used to predict the ADME and toxicity activity of compound 1. The results suggested that compound 1 was biocompatible and had poor toxicity, which was verified by rat INS-1 islet ß cells through an MTT assay. Meanwhile, a significant stimulatory effect on INS-1 cells was observed, which indicated a hypoglycemic effect of compound 1. This is the first report that describes a natural, novel, and hypoglycemic phenylethanoid glycoside in Stevia.

Biomarkers of metal toxicity in embryos in the general population.

BACKGROUND: With the development of industrialization, public exposure to toxic metals could occur everywhere, eventually affecting individuals' reproductive systems and even embryos and leading to early pregnancy loss. The aim of the study was to determine the profile of toxic metal levels in pregnant women in the general population and to identify biomarkers for metal toxicity in embryos. METHODS: A case-control study with pregnant women was conducted at Peking Union Medical College Hospital in 2016-2018. Women who experienced spontaneous abortion within 12 weeks of gestation comprised the case group, and women with pregnancies showing fetal cardiac activity who requested an induced abortion almost simultaneously were included in the control group. Blood and urine specimen were tested for concentrations of cadmium, chromium, selenium, arsenic, and mercury. RESULTS: A total of 195 patients were enrolled, with 95 in the case group and 100 in the control group. Significant differences in gravidity, parity, history of miscarriage, mean blood cadmium levels, and mean urine chromium levels were present between the two groups (P1 = 0.013, P2 = 0.000, P3 = 0.000, P4 = 0.002, P5 = 0.046); the odds ratios in the spontaneous abortion with blood cadmium >0.4 µg/L, urine chromium >2 µg/L, gravity <3, parity <2, and history of miscarriage >1 compared with the induced abortion group were 1.26 (1.09, 1.85), 1.56 (1.23, 2.53), 1.39 (1.17, 1.98), 1.72 (1.21, 4.62), and 1.18 (1.06, 1.65), with P-values of 0.003, 0.031, 0.003, 0.247, and 0.001, respectively. CONCLUSION: Blood cadmium and urine chromium levels are two possible biomarkers of toxic metal embryotoxicity in the general population, which means that in the general population, blood cadmium >0.4 µg/L or urine chromium >2 µg/L might indicate an increased risk of spontaneous abortion.

[Quality characterization analysis of single decoction and merger decoction of Baihu and Guizhi].

To study the differences and similarities in pharmaceutical characterization and pharmacodynamic characterization between the single decoction and merger decoction of Baihu and Guizhi. The same technology parameters were used to prepare Baihu and Guizhi single decoticon and merger decoction extracts, and then the differences and similarities in pharmaceutical characterization were analyzed based on their HPLC fingerprint, content of index components, and the extraction content. The pharmacodynamic differences and similarities were analyzed by inflammatory model and pain model. There was no significant difference in HPLC chromatographic peak, but the peak area value reflected the difference of quantity to some extent. It was found that the peak value of single Rhizoma anemarrhenae and Cassia twig decoction was less than the peak of their merger decoction, but the peak value of single honey-fried Licorice root decoction was greater than the peak of merger decoction． The contents of neomangiferin, mangiferin and timosaponin B Ⅱ among index components as well as extraction content in merger decoction were higher than those in single decoction． The contents of liquiritin and glycyrrhizic acid as well as extraction content in merger decoction were lower than those in single decoction． There was no significant difference in the content of cinnamicacid and its extraction content between merger decoction and single decoction. According to the efficacy experiment, both of them showed significant anti-inflammatory and analgesic effects. However, the merger decoction showed faster anti-inflammation effect, and longer analgesic effect. It can be concluded that the merger decoction and single decoction of Baihu and Guizhi have the same material basis, and the merger decoction is better for the dissolution of the active ingredients in this recipe, and is more beneficial to the therapeutic effect.

Prevalence of Pain and Effects of a Brief Mindfulness-Based Intervention on Chinese Community-Dwelling Older Adults with Chronic Pain.

This study aimed to screen the prevalence of pain in Chinese community-dwelling older adults and to evaluate the effects of a brief mindfulness-based intervention on chronic pain. The prevalence of pain among Chinese older adults was 40.5%. The brief mindfulness intervention had significant effects on reducing pain intensity (P = 0.004), and increasing the mindfulness measures: observing, acting with awareness, non-judging and non-reactivity inner experience (all P values < 0.05). Pain prevalence among Chinese older adults was relatively high. This study showed that a brief mindfulness-based intervention reduced ratings of pain intensity and enhanced ratings of the perception of mindfulness.

Two new oxygen-containing biomarkers isolated from the Chinese Maoming oil shale by silica gel column chromatography and preparative gas chromatography.

Two biomarkers, 5,9-dimethyl-6-isopropyl-2-decanone (1) and 4,9,11-trimethyl-6-isopropyl-2-dodecanone (2), were isolated from Chinese Maoming oil shale by silica gel column chromatography and preparative gas chromatography. Their structures were elucidated by using spectroscopic techniques.

Black carbon and kerogen in soils and sediments. 2. Their roles in equilibrium sorption of less-polar organic pollutants.

The first paper of this series reported that soil/sediment organic matter (SOM) can be fractionated into four fractions with a combined wet chemical procedure and that kerogen and black carbon (BC) are major SOM components in soil/sediment samples collected from the industrialized suburban areas of Guangzhou, China. The goal of this study was to determine the sorptive properties forthe four SOM fractions for organic contaminants. Sorption isotherms were measured with a batch technique using phenanthrene and naphthalene as the sorbates and four original and four Soxhlet-extracted soil/sediment samples, 15 isolated SOM fractions, and a char as the sorbents. The results showed that the sorption isotherms measured for all the sorbents were variously nonlinear. The isolated humic acid (HA) exhibited significantly nonlinear sorption, but its contribution to the overall isotherm nonlinearity and sorption capacity of the original soil was insignificant because of its low content in the tested soils and sediments. The particulate kerogen and black carbon (KB) fractions exhibited more nonlinear sorption with much higher organic carbon-normalized capacities for both sorbates. They dominate the observed overall sorption by the tested soils and sediments and are expected to be the most important soil components affecting bioavailability and ultimate fate of hydrophobic organic contaminants (HOCs). The fact that the isolated KB fractions exhibited much higher sorption capacities than when they were associated with soil/sediment matrixes suggested that a large fraction of the particulate kerogen and BC was not accessible to sorbing HOCs. Encapsulation within soil aggregates and surface coverage by inorganic and organic coatings may have caused large variations in the accessibility of fine kerogen and BC particles to HOCs and hence lowered the sorption capacity of the soil. This variability posts an ultimate challenge for precisely predicting HOC sorption by soils from the contents of different types of SOM.

Black carbon and kerogen in soils and sediments. 1. Quantification and characterization.

A comprehensive wet chemical procedure was developed by combining acid demineralization, base extraction, and dichromate oxidation for fractionation and quantitative isolation of soil/sediment organic matter (SOM) into four fractions: (1) humic acids + kerogen + BC (HKB); (2) kerogen + BC (KB); (3) humic acid (HA); and (4) BC. The soil/sediment samples tested were collected from the suburban areas of Guangzhou, a rapidly developing city of China. The results show that BC and kerogen constitute 57.8-80.6% of the total organic carbon (TOC) and that the relative content of BC ranges from 18.3% to 41.0% of the TOC, indicating that both BC and kerogen are major organic components in soils and sediments from this industrialized region. Systematic characterization of the isolated SOMs shows that both BC and kerogen have sizes ranging from a few microns to above 100 microm, relatively low O/C and H/C atomic ratios, and low contents of oxygen-containing functional groups. The isolated BC has unique fusinite and semifusinite macerals, highly porous nature, and structures indicative of its possible origins. The study indicates that SOM is highly heterogeneous and that humin, the nonextractable humus fraction, consists mainly of kerogen and BC materials in the tested soil/sediment samples. The presence of these materials in soils and sediments may have significant impacts on pollutant mass transfer and transformation processes such as desorption and bioavailability of less polar organic chemicals in surface aquatic and groundwater environments.