Huaixiu Wen

Erythritol Attenuates Postprandial Blood Glucose by Inhibiting α-Glucosidase

Diabetes mellitus (DM) is a serious metabolic disorder, where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical erythritol is a C4 polyol approved by the U.S. Food and Drug Administration for use as a sweetener. Here, we examined a potential role for erythritol in the control of postprandial blood glucose levels in DM. An anti-postprandial hyperglycemia effect upon erythritol administration (500 mg kg-1) was demonstrated in alloxan-induced DM model mice by monitoring changes in blood glucose after intragastric administration of drugs and starch. We also found that erythritol most likely exerts its anti-postprandial hyperglycemic activities by inhibiting α-glucosidase in a competitive manner. This was supported by enzyme activity assays and molecular modeling experiments. In the latter experiments, it was possible to successfully dock erythritol into the catalytic pocket of α-glucosidase, with the resultant interaction likely driven by electrostatic interactions involving Asp215, Asp69, and Arg446 residues. This study suggests that erythritol may not only serve as a glucose substitute but also be a useful agent in the treatment of DM to help manage postprandial blood glucose levels.

Phenolics from Lagotis brevituba Maxim.

Abstract A phytochemical investigation on Lagotis brevituba led to the isolation and characterisation of 11 phenolic compounds: p-hydroxy-benzoic acid 1, methyl 3,4-dihydroxybenzoate 2, vanillic acid 3, protocatechuic acid 4, caffeic acid 5, glucose ester of (E)-ferulic acid 6, p-coumaric acid 7, vanillin 8, diosmetin-7-O-β-d-glucoside 9, chrysoeriol 10 and luteolin 11. Their structures were elucidated using spectroscopic methods and by comparison with data in the literature. Compounds 1–6 were first obtained from the genus Lagotis, and compounds 1–9 were isolated from L. brevituba for the first time. Compound 4 and 11 displayed remarkable antioxidant activities against DPPH radical (IC50 = 5.60 ± 0.09, 27.5 ± 0.06 mg/L, respectively), which were superior to positive control rutin. And compound 11 was also superior to rutin in ABTS assay (IC50 = 2.04 ± 0.13 mg/L).

Antihypoxic activities of constituents from Arenaria kansuensis

BACKGROUND In previous investigation, we have identified antioxidative effects of water-soluble ethanolic extracts (named as AKE) from Arenaria kansuensis and inferred that these extracts or their constituents may also have antihypoxic activity. A. kansuensis has been widely used in traditional Tibetan medicine for altitude sickness (AS) and has been known as the herb of anti-inflammatory and hypoxia resistance for a long time. PURPOSE The purpose of this study is to evaluate protective effects of AKE and its major constituents against hypoxia-induced lethality in mice and RSC96 cells. STUDY DESIGN AND METHODS Hypoxia-induced lethality in mice was investigated by 3 experimental animal models of hypoxia. Meanwhile, we established a RSC96 cell model of hypoxia which applied to screen and assess the anti-hypoxic activity of compounds isolated from A. kansuensis. RESULTS Results indicated that AKE dose-dependently prolonged survival time of hypoxia induced lethality in mice compared to vehicle group and exhibited significantly anti-hypoxic effect. AKE also enhanced the number of red blood cells (RBC) and the concentration of hemoglobin (HB). 8 compounds were bio-guided separated and purified from AKE based on the animal model and cell model of hypoxia. Among which pyrocatechol (C16) and tricin 7-O-β-d-glucopyranoside (C13) were confirmed to express better protective effects on cell damage induced by hypoxia, suggesting that these two compounds are major active constituents of AKE for anti-hypoxia. CONCLUSION This study demonstrated that pyrocatechol and tricin 7-O-β-d-glucopyranoside could be therapeutic candidates for treatment of AS. It is the first time to find the major active constituents of AKE for anti-hypoxia. Meanwhile, a RSC96 cell model of hypoxia was established to screen anti-hypoxic activity of compounds for the first time.

Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi.

Traditional Tibetan medicine provides an abundant source of knowledge on human ailments and their treatment. As such, it is necessary to explore their active single compounds used to treat these ailments to discover lead compounds with good pharmacologic properties. In this present work, animal medicine, Osteon Myospalacem Baileyi extracts have been separated using a two‐dimensional preparative chromatographic method to obtain single compounds with high purity as part of the following pharmacological research. Five high‐purity cyclic dipeptides from chromatography work were studied for their dihydroorotate dehydrogenase inhibitory activity on recombinant human dihydroorotate dehydrogenase enzyme and compound Fr. 1‐4 was found to contain satisfying inhibition activity. The molecular modeling study suggests that the active compound Fr. 1‐4 may have a teriflunomide‐like binding mode. Then, the energy decomposition study suggests that the hydrogen bond between Fr. 1‐4 and Arg136 can improve the binding mode to indirectly increase the van der Waals binding energy. All the results above together come to the conclusion that the 2, 5‐diketopiperazine structure group can interact with the polar residues well in the active pocket using electrostatic power. If some proper hydrophobic groups can be added to the sides of the 2, 5‐diketopiperazine group, it is believed that better 2, 5‐diketopiperazine dihydroorotate dehydrogenase inhibitors will be found in the future.

Anti-inflammatory activity of total alkaloids from Hypecoum leptocarpum hook. f. et Thoms

Background: Puerariae Lobatae Radix is widely used in the pharmaceutical, food, and cosmetic industries. For these applications, when grading roots according to diameter, thick roots are always considered to be of better quality. Objective: The objective of this study is to qualitative and quantitative analysis of isoflavonoids profiling in various tissues of P. lobata roots. Materials and Methods: Ultraperformance liquid chromatography quadrupole/time-of-flight-mass spectrometry (UPLC-QTOF/MS) and high-performance liquid chromatography separation and ultraviolet-visible detection were used to identify and profile the isoflavonoids detected in various tissues of P. lobata roots. Results: Consequently, 82 peaks were detected by UPLC-QTOF/MS, and 28 isoflavonoid compounds were identified in the various tissue samples. According to the results of this study, the thick roots of P. lobata are of better quality for medical use than the thin ones. The fine roots and the periderm of roots contained slightly lower isoflavonoid abundances. The results indicated that isoflavonoids, particularly puerarin, mainly accumulated in the xylem and phloem. Conclusions: This study provides a new and practical method for evaluating the quality of P. lobatae Radix. Abbreviations used: ANOVA: One-way analysis of variance; CNKI: Chinese National Knowledge Infrastructure; HPLC-UV: High performance liquid chromatography separation and ultraviolet-visible detection; PPRC: Pharmacopoeia of the Peoples Republic of China; RSD: Relative standard deviation; UPLC-QTOF/MS: Ultraperformance liquid chromatography quadrupole/time-of-flight-mass spectrometry.