The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine

Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.     

Maternal Physiological Variations Induced by Chronic Gestational Hypoxia: 1H NMR-Based Metabolomics Study

Metabolomics have been widely used in pregnancy-related diseases. However, physiological variations induced by chronic hypoxia during pregnancy are not well characterized. We aimed to investigate physiological variations induced by chronic hypoxia during pregnancy. A Sprague–Dawley (SD) pregnant rat model of chronic hypoxia was established. Plasma and urine metabolite profiles at different stages of the pregnancy were detected by ¹H NMR (nuclear magnetic resonance). Multivariate statistical analysis was used to analyze changes in plasma and urine metabolic trajectories at different time-points. We identified hypoxia-induced changes in the levels of 30 metabolites in plasma and 29 metabolites in urine during different stages of pregnancy; the prominently affected metabolites included acetic acid, acetone, choline, citric acid, glutamine, isoleucine, lysine, and serine. Most significant hypoxia-induced changes in plasma and urine sample metabolites were observed on the 11th day of gestation. In summary, chronic hypoxia has a significant effect on pregnant rats, and may cause metabolic disorders involving glucose, lipids, amino acids, and tricarboxylic acid cycle. Metabolomics study of the effect of hypoxia during pregnancy may provide insights into the pathogenesis of obstetric disorders.     

Effect of Co-Existing Cations and Anions on the Adsorption of Antibiotics on Iron-Containing Minerals

The adsorption of antibiotics on minerals is an important process in their environment behavior. The adsorption behavior of antibiotics on iron-containing minerals and the effect of co-existing cations and anions were studied in this work. Magnetite, hematite, goethite and kaolin were selected as the representative minerals and characterized by SEM, XRD and BET. A total of eight antibiotics, including three quinolones, three sulfonamides and two mycins were chosen as the research targets. Results showed a higher adsorption amount of quinolones than that of sulfonamides and mycins on the surface of iron-containing minerals in most mineral systems. The adsorption isotherms of quinolones can be well fitted using the Freundlich models. The effects of five cations and five anions on the adsorption of quinolones were investigated, among which Mg²⁺, Ca²⁺, HCO₃⁻ and H₂PO₄⁻ mainly showed significant inhibition on the adsorption, while the effects of K⁺, Na⁺, NH₄⁺, Cl⁻, NO₃⁻ and SO₄²⁻ showed less. Natural surface water samples were also collected and used as media to investigate the adsorption behavior of quinolones on iron-containing minerals. The buffering capacity of the natural water kept the reaction solution at circumneutral conditions, and the adsorption amount was mostly promoted in the goethite system (from 0.56~0.78 μmol/g to 0.52~1.43 μmol/g), but was inhibited in the other systems (magnetite: from 1.13~1.33 μmol/g to 0.45~0.76 μmol/g; hematite: from 0.52~0.65 μmol/g to 0.02~0.18 μmol/g; kaolin: from 1.98~1.99 μmol/g to 0.90~1.40 μmol/g). The results in this work help to further understand the transportation and fate of antibiotics in an aqueous environment.     

Pentapeptide-Zinc Chelate from Sweet Almond Expeller Amandin Hydrolysates: Structural and Physicochemical Characteristics,Stability and Zinc Transport Ability In Vitro

To promote the application of almond expellers, sweet almond expeller globulin (amandin) was extracted for the preparation of bioactive peptides. After dual enzymatic hydrolysis, Sephadex G-15 gel isolation, reverse-phase high-performance liquid chromatography purification and ESI-MS/MS analysis, two novel peptides Val-Asp-Leu-Val-Ala-Glu-Val-Pro-Arg-Gly-Leu (1164.45 Da) and Leu-Asp-Arg-Leu-Glu (644.77 Da) were identified in sweet almond expeller amandin hydrolysates. Leu-Asp-Arg-Leu-Glu (LDRLE) of excellent zinc-chelating capacity (24.73 mg/g) was selected for preparation of peptide-zinc chelate. Structural analysis revealed that zinc ions were mainly bonded to amino group and carboxyl group of LDRLE. Potential toxicity and some physicochemical properties of LDRLE and Val-Asp-Leu-Val-Ala-Glu-Val-Pro-Arg-Gly-Leu (VDLVAEVPRGL) were predicted in silico. The results demonstrated that both LDRLE and VDLVAEVPRGL were not toxic. Additionally, zinc solubility of LDRLE-zinc chelate was much higher than that of zinc sulphate and zinc gluconate at pH 6.0–10.0 and against gastrointestinal digestion at 37 °C (p < 0.05). However, incubation at 100 °C for 20–60 min significantly reduced zinc-solubility of LDRLE-zinc chelate. Moreover, the chelate showed higher zinc transport ability in vitro than zinc sulphate and zinc gluconate (p < 0.05). Therefore, peptides isolated from sweet almond expeller amandin have potential applications as ingredient of zinc supplements.     

Control Efficacy of Salicylic Acid Microcapsules against Postharvest Blue Mold in Apple Fruit

Salicylic acid (SA) is a natural inducer of disease resistance in fruit, but its application in the food industry is limited due to low water solubility. Here, SA was encapsulated in β-cyclodextrin (β-CD) via the host–guest inclusion complexation method, and the efficacy of SA microcapsules (SAM) against blue mold caused by Penicillium expansum in postharvest apple fruit was elucidated. It was observed that SAM was the most effective in inhibiting the mycelial growth of P. expansum in vitro. SAM was also superior to SA for control of blue mold under in vivo conditions. Enzyme activity analysis revealed that both SA and SAM enhanced the activities of superoxide dismutase (SOD) and phenylalanine ammonia lyase (PAL) in apple fruit, whereas SAM led to higher SOD activities than SA. Total phenolic contents in the SAM group were higher than those in the SA group at the early stage of storage. SAM also improved fruit quality by retarding firmness loss and maintaining higher total soluble solids (TSS) contents. These findings indicate that microcapsules can serve as a promising formulation to load SA for increasing P. expansum inhibition activity and improving quality attributes in apple fruit.     

Semisynthesis and Pesticidal Activities of Novel Cholesterol Ester Derivatives Containing Cinnamic Acid-like Fragments

Due to the extensive use of agrochemicals resulting in the emergence of pesticide resistance and ecological environment problems, the research and development of new alternatives for crop protection is highly desirable. In order to discover potent natural product-based insecticide candidates, a series of new cholesterol ester derivatives containing cinnamic acid-like fragments at the C-7 position were synthesized. Some derivatives showed potent pesticidal activities. Against Mythimna separata Walker, compounds 2a, Id, Ig, and IIg showed 2.1–2.4-fold growth-inhibitory activity of the precursor cholesterol. Against Plutella xylostella Linnaeus, compounds Ig, IIf, and IIi exhibited 1.9–2.1-fold insecticidal activity of cholesterol. These results will pave the way for the future synthesis of cholesterol-based derivatives as agrochemicals.     

By-Product of the Red Ginseng Manufacturing Process as Potential Material for Use as Cosmetics: Chemical Profiling and In Vitro Antioxidant and Whitening Activities

Red ginseng (RG), which is obtained from heated Panax ginseng and is produced by steaming followed by drying, is a valuable herb in Asian countries. Steamed ginseng dew (SGD) is a by-product produced in processing red ginseng. In the present study, phytochemical profiling of extracts of red ginseng and steamed ginseng dew was carried out using gas chromatography-mass spectrometry (GC-MS) and rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) analysis. Additionally, antioxidant activities (DPPH, ·OH, and ABTS scavenging ability) and whitening activities (tyrosinase and elastase inhibitory activity) were analyzed. Phytochemical profiling revealed the presence of 66 and 28 compounds that were non-saponin components in chloroform extracts of red ginseng and steamed ginseng dew (RG-CE and SGD-CE), respectively. Meanwhile, there were 20 ginsenosides identified in n-butanol extracts of red ginseng and steamed ginseng dew (RG-NBE and SGD-NBE). By comparing the different polar extracts of red ginseng and steamed ginseng dew, it was found that the ethyl acetate extract of red ginseng (RG-EAE) had the best antioxidant capacity and whitening effect, the water extract of steamed ginseng dew (SGD-WE) had stronger antioxidant capacity, and the SGD-NBE and SGD-CE had a better whitening effect. This study shows that RG and SGD have tremendous potential to be used in the cosmetic industries.     

Pseudognaphalium affine Extract Alleviates COPD by Inhibiting the Inflammatory Response via Downregulation of NF-κB

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with limited therapeutic options. Pseudognaphalium affine (D. Don) Anderb. is a medicinal and edible plant used to treat cough, asthma, and COPD for a long time in folk medicine. The objective of this study is to evaluate the effect of Pseudognaphalium affine (D. Don) Anderb. extract (GAE) and investigate the possible underlying mechanism in vivo and in vitro. In vivo, the administration of GAE in a rat COPD model could significantly ameliorate lung damage and pulmonary function by inhibiting the production of pro-inflammatory cytokines. Western blot and real-time PCR results showed that GAE could suppress nuclear translocation of nuclear factor-kappa B (NF-κB), which indicated that GAE down-regulated the NF-κB pathway. Moreover, GAE protected against tumor necrosis factor (TNF)-α induced inflammatory response in BEAS-2B and inhibited the NF-κB pathway. All data suggested that GAE exhibited its anti-COPD effect by inhibiting pro-inflammatory cytokines, which may be associated with the inhibition of the NF-κB pathway.     

Molecular Cloning,Expression, and Functional Analysis of Glycosyltransferase (TbUGGT) Gene from Trapa bispinosa Roxb.

Trapa bispinosa Roxb. is an economical crop for medicine and food. Its roots, stems, leaves, and pulp have medicinal applications, and its shell is rich in active ingredients and is considered to have a high medicinal value. One of the main functional components of the Trapa bispinosa Roxb. shell is 1-galloyl-beta-D-glucose (βG), which can be used in medical treatment and is also an essential substrate for synthesizing the anticancer drug beta-penta-o-Galloyl-glucosen (PGG). Furthermore, gallate 1-beta-glucosyltransferase (EC 2.4.1.136) has been found to catalyze gallic acid (GA) and uridine diphosphate glucose (UDPG) to synthesize βG. In our previous study, significant differences in βG content were observed in different tissues of Trapa bispinosa Roxb. In this study, Trapa bispinosa Roxb. was used to clone 1500 bp of the UGGT gene, which was named TbUGGT, to encode 499 amino acids. According to the specificity of the endogenous expression of foreign genes in Escherichia coli, the adaptation codon of the cloned original genes was optimized for improved expression. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbUGGT with squalene synthases from other plants. The TbUGGT gene was constructed into a PET-28a expression vector and then transferred into Escherichia coli Transsetta (DE3) for expression. The recombinant protein had a molecular weight of 55 kDa and was detected using SDS-PAGE. The proteins were purified using multiple fermentation cultures to simulate the intracellular environment, and a substrate was added for in vitro reaction. After the enzymatic reaction, the levels of βG in the product were analyzed using HPLC and LC-MS, indicating the catalytic activity of TbUGGT. The cloning and functional analysis of TbUGGT may lay the foundation for further study on the complete synthesis of βG in E. coli.     

Urea Synthesis from Isocyanides and O-Benzoyl Hydroxylamines Catalyzed by a Copper Salt

In the presence of CuOAc, a series of unsymmetric ureas can be generated in moderate to good yields under mild reaction conditions (10 mol% of CuOAc, 2 equiv t-BuONa or PhONa, 30 °C), using aryl isocyanides and O-benzoyl hydroxylamines as the readily accessible starting materials. The reactions might undergo a cascade process involving isocyanide insertion into the N-O bond and Mumm-type rearrangement. This work represents a rare example of isocyanide insertion into N-O bonds, which would extend isocyanide insertion chemistry.