Phenolic constituents from the branches of Viburnum chinshanense as potential α-amylase and α-glucosidase inhibitory agents.

This paper reports the isolation of two undescribed phenolic glycosides (1 and 2), together with seven known compounds (3-9) from the branches of Viburnum chinshanense. The structures of undescribed compounds were elucidated by comprehensive spectroscopic methods (1D NMR, 2D NMR, and HRESIMS). The sugar units of compounds 1 and 2 were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of the monosaccharides. Furthermore, the α­amylase and α-glucosidase inhibitory activities of all isolates were evaluated and compounds 1, 5, and 8 displayed potential α­amylase and α-glucosidase inhibitory activities. The molecular docking analyses of compounds 1 and 8 with the potent inhibition towards the target enzymes were also performed.

Phenolic Glycosides from Viburnum chinshanense Leaves and their α-Amylase and α-Glucosidase Inhibitory Activity.

The phytochemical investigation of Viburnum chinshanense leaves led to the isolation and identification of four new phenolic glycosides, viburninsides A-D (1-4), and eight known analogues (5-12). The structures of the four undescribed compounds were determined by spectroscopic techniques, including 1D NMR, 2D NMR, and HRESIMS, and their containing sugar units were confirmed by acid hydrolysis and HPLC analysis of the monosaccharide's chiral derivatives. Additionally, the α-amylase and α-glucosidase inhibitory activities of the isolated compounds were assessed. Compounds 1, 2, 4, 9, and 10 exhibited potential inhibitory activities against α-amylase and α-glucosidase with IC50 values ranging from 35.07 µM to 47.42 µM and 18.27 µM to 43.65 µM, respectively. Molecular docking analysis of compound 4 with the strongest inhibition against the target enzymes was also conducted.

Maternal GLP-1 receptor activation inhibits fetal growth.

Glucagon-like peptide 1 (GLP-1) regulates food intake, insulin production, and metabolism. Our recent study demonstrated that pancreatic α-cells-secreted (intraislet) GLP-1 effectively promotes maternal insulin secretion and metabolic adaptation during pregnancy. However, the role of circulating GLP-1 in maternal energy metabolism remains largely unknown. Our study aims to investigate systemic GLP-1 response to pregnancy and its regulatory effect on fetal growth. Using C57BL/6 mice, we observed a gradual decline in maternal blood GLP-1 concentrations. Subsequent administration of the GLP-1 receptor agonist semaglutide (Sem) to dams in late pregnancy revealed a modest decrease in maternal food intake during initial treatment. At the same time, no significant alterations were observed in maternal body weight or fat mass. Notably, Sem-treated dams exhibited a significant decrease in fetal body weight, which persisted even following the restoration of maternal blood glucose levels. Despite no observable change in placental weight, a marked reduction in the placenta labyrinth area from Sem-treated dams was evident. Our investigation further demonstrated a substantial decrease in the expression levels of various pivotal nutrient transporters within the placenta, including glucose transporter one and sodium-neutral amino acid transporter one, after Sem treatment. In addition, Sem injection led to a notable reduction in the capillary area, number, and surface densities within the labyrinth. These findings underscore the crucial role of modulating circulating GLP-1 levels in maternal adaptation, emphasizing the inhibitory effects of excessive GLP-1 receptor activation on both placental development and fetal growth.NEW & NOTEWORTHY Our study reveals a progressive decline in maternal blood glucagon-like peptide 1 (GLP-1) concentration. GLP-1 receptor agonist injection in late pregnancy significantly reduced fetal body weight, even after restoration of maternal blood glucose concentration. GLP-1 receptor activation significantly reduced the placental labyrinth area, expression of some nutrient transporters, and capillary development. Our study indicates that reducing maternal blood GLP-1 levels is a physiological adaptation process that benefits placental development and fetal growth.

Lignan and phenolic glycosides from Viburnum betulifolium fruits and their α­amylase and α-glucosidase inhibitory activities.

The phytochemical investigation on the methanol extract of Viburnum betulifolium fruits resulted in the isolation and identification of two new lignan constituents (1 and 2) and seven known phenolic glycosides (3-9). The structures of new isolates, including their absolute configurations were elucidated by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ECD) and chemical methods. In the in vitro enzyme assays, compounds 1, 2, 6, and 8 showed potential α­amylase and α-glucosidase inhibitory activities. Among them, compound 1 exhibited stronger inhibitory effects towards α-amylase and α-glucosidase with the IC50 values of 12.68 and 15.17 µM, respectively, than those of the positive control acarbose (IC50, 29.19 and 18.15 µM, respectively). In addition, the molecular docking analyses of compound 1 with strongest inhibition against the target enzymes were also performed.

Lignan constituents with α-amylase and α-glucosidase inhibitory activities from the fruits of Viburnum urceolatum.

Eleven previously undescribed lignan constituents, including five 8-O-4' type neolignans, viburnurcosides A-E (1-5), three benzofuran type neolignans, viburnurcosides F-H (6-8), and three tetrahydrofuran type lignans, viburnurcosides I-K (9-11), were isolated from the fruits of Viburnum urceolatum. The structures of all isolates were elucidated by an extensive analysis of the NMR and HRESIMS data. The absolute configurations of these compounds were determined by quantum-chemical electronic circular dichroism calculation and comparison. The sugar units of viburnurcosides A-K were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of monosaccharides. The in vitro enzyme inhibition assay exhibited that viburnurcoside J (10) had the most potent inhibitory activity against α-amylase and α-glucosidase with the IC50 values of 19.75 and 9.14 µM, respectively, which were stronger than those of the positive control acarbose (37.31 and 26.75 µM, respectively). The potential binding modes of viburnurcoside J (10) with α-amylase and α-glucosidase were also analyzed by molecular modeling.

Iridoid constituents from the branches of Viburnum chinshanense and their inhibitory effects on α-amylase and α-glucosidase.

Ten previously undescribed iridoid constituents, viburnshosins A-E (1-5) and viburnshosides A-E (6-10), together with one known analogue (11), were isolated from the branches of Viburnum chinshanense. Their structures were unambiguously elucidated by a comprehensive analysis of 1D and 2D NMR data, together with HRESIMS spectroscopic data. The absolute configurations of compounds 1-10 were assigned by means of the calculated ECD spectra. Interestingly, compounds 2 and 3 are the first iridoids with an unusual C-3-C-7 oxo bridge. Compounds 4, 5, and 10 displayed remarkable inhibitory effects against α-amylase (IC50: 38.42, 37.65, and 21.64 µM, respectively) and α-glucosidase (IC50: 12.97, 19.34, and 25.71 µM, respectively), comparable to those of the positive control acarbose (IC50: 39.75 and 23.66 µM, respectively). The interaction modes of compounds 4 and 10 with two enzymes were analyzed by molecular modeling.

Study on Quasi-Static Axial Compression Performance and Energy Absorption of Aluminum Foam-Filled Steel Tubes.

To study the axial compression performance of aluminum foam-filled steel tube and empty steel tube as objects, such tubes are studied in this paper, which explores the carrying capacity and deformation behavior of aluminum foam-filled steel tube with different lengths under a quasi-static axial load through experimental research. The carrying capacity, deformation behavior, stress distribution, and energy absorption characteristics of empty steel tubes and foam-filled steel tubes are compared through finite element numerical simulation. The results indicate that, compared with the empty steel tube, the aluminum foam-filled steel tube still presents a large residual carrying capacity after the axial force exceeds the ultimate load, and the whole compression process reflects steady-state compression. In addition, the axial and lateral deformation amplitudes of the foam-filled steel tube decrease significantly during the whole compression process. After filling the foam metal, the large stress area decreases and the energy absorption capacity improves.

Five New Phenolic Glycosides from Viburnum luzonicum.

Viburnum luzonicum is widely distributed in China. Its branch extracts showed potential α-amylase and α-glucosidase inhibitory activities. In order to discover new bioactive constituents, five undescribed phenolic glycosides, viburozosides A-E (1-5), were obtained by bioassay-guided isolation coupled with HPLC-QTOF-MS/MS analysis. Their structures were elucidated by spectroscopic analyses, including 1D NMR, 2D NMR, ECD, and ORD. All compounds were tested for their α-amylase and α-glucosidase inhibitory potency. Compound 1 showed significantly competitive inhibition against α-amylase (IC50 =17.5 µM) and α-glucosidase (IC50 =13.6 µM).

LC-MS guided isolation of phenolic glycosides from Viburnum luzonicum Rolfe leaves and their α­amylase and α-glucosidase inhibitory activities.

Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n-BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit α­amylase and α-glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C (1-3), along with seven known analogues (4-10) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1-8 showed potent α­amylase and α-glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.

Two new phenolic allopyranosides and their analogues from the stems of Viburnum luzonicum Rolfe guided by LC-MS.

Two new phenolic allopyranosides, named viburluzosides A and B (1, 2), together with eight known phenolic glycosides (3 - 10) were discovered from the stems of Viburnum luzonicum Rolfe under the guidance of LC-MS analyses coupled with bioactivity evaluation. They were purified through various chromatography methods and identified by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, and HRESIMS) and chemical methods. The in vitro evaluation on α-glucosidase and aldose reductase (AR) inhibitory activities of isolated compounds were conducted. Compounds 1 - 4 and 6 - 9 exhibited α-glucosidase inhibitory activities with IC50 values of 5.35 - 21.34 µM and AR inhibitory activities with IC50 values of 6.21 - 40.06 µM. Moreover, the inhibitory kinetics analyses of compounds 1 and 2 were also performed.

Recent Advances of Interface Exciplex in Organic Light-Emitting Diodes.

The interface exciplex system is a promising technology for reaching organic light-emitting diodes (OLEDs) with low turn-on voltages, high efficiencies and long lifetimes due to its unique virtue of barrier-free charge transport, well-confined recombination region, and thermally activated delayed fluorescence characteristics. In this review, we firstly illustrate the mechanism frameworks and superiorities of the interface exciplex system. We then summarize the primary applications of interface exciplex systems fabricated by doping and doping-free technologies. The operation mechanisms of these OLEDs are emphasized briefly. In addition, various novel strategies for further improving the performances of interface exciplex-based devices are demonstrated. We believe this review will give a promising perspective and attract researchers to further develop this technology in the future.

The Essential Role of Pancreatic α-Cells in Maternal Metabolic Adaptation to Pregnancy.

Pancreatic α-cells are important in maintaining metabolic homeostasis, but their role in regulating maternal metabolic adaptations to pregnancy has not been studied. The objective of this study was to determine whether pancreatic α-cells respond to pregnancy and their contribution to maternal metabolic adaptation. With use of C57BL/6 mice, the findings of our study showed that pregnancy induced a significant increase of α-cell mass by promoting α-cell proliferation that was associated with a transitory increase of maternal serum glucagon concentration in early pregnancy. Maternal pancreatic GLP-1 content also was significantly increased during pregnancy. Using the inducible Cre/loxp technique, we ablated the α-cells (α-null) before and during pregnancy while maintaining enteroendocrine L-cells and serum GLP-1 in the normal range. In contrast to an improved glucose tolerance test (GTT) before pregnancy, significantly impaired GTT and remarkably higher serum glucose concentrations in the fed state were observed in α-null dams. Glucagon receptor antagonism treatment, however, did not affect measures of maternal glucose metabolism, indicating a dispensable role of glucagon receptor signaling in maternal glucose homeostasis. However, the GLP-1 receptor agonist improved insulin production and glucose metabolism of α-null dams. Furthermore, GLP-1 receptor antagonist Exendin (9-39) attenuated pregnancy-enhanced insulin secretion and GLP-1 restored glucose-induced insulin secretion of cultured islets from α-null dams. Together, these results demonstrate that α-cells play an essential role in controlling maternal metabolic adaptation to pregnancy by enhancing insulin secretion.

Recent Advance on Chemistry and Bioactivities of Secondary Metabolites from Viburnum Plants: An Update.

Viburnum species are a group of small trees or shrubs that are of great ornamental and medicinal values. Some of them have been used for a long time both as conventional and ethnic medicine. Viburnum fruits, eaten in fresh and processed forms, have been revealed to contain various health-promoting nutrients. With the increasing research on Viburnum plants, they are considered to be an abundant resource of bioactive natural products possessing diverse pharmacological properties and unique chemical structures, that is powerfully proved by the existence of structurally novel vibsane-type diterpenoids which only occur in Viburnum species, newly discovered lignan constituents with unusual side chains and other noteworthy natural components. This review describes 185 new and 228 known secondary metabolites from Viburnum genus between 2008 and 2020, including their chemical structures, sources and bioactivities, and highlights the corresponding structure-activity relationships.

Adiponectin Promotes Maternal ß-Cell Expansion Through Placental Lactogen Expression.

Hypoadiponectinemia is a risk factor of gestational diabetes mellitus (GDM). Our previous study reported that adiponectin gene knockout mice (Adipoq -/- ) develop GDM due to insulin insufficiency. The main objective of this study was to elucidate the underlying mechanism through which adiponectin controls islet expansion during pregnancy. A significant reduction in ß-cell proliferation rates, ß-cell areas, and blood insulin concentrations was detected in Adipoq -/- mice at midpregnancy. Surprisingly, conditionally knocking down adiponectin receptor 1 (AdipoR1) or AdipoR2 genes in ß-cells during pregnancy did not reduce ß-cell proliferation rates or blood insulin concentrations. In vitro adiponectin treatment also failed to show any effect on ß-cell proliferation of isolated pancreatic islets. It was reported that placental lactogen (PL) plays a crucial role in pregnancy-induced maternal ß-cell proliferation. A significant decrease in phosphorylation of signal transducer and activator of transcription 5, a downstream molecule of PL signaling, was observed in islets from Adipoq -/- dams. The mRNA levels of mouse PL genes were robustly decreased in the placentas of Adipoq -/- dams. In contrast, adiponectin treatment increased PL expression in human placenta explants and JEG3 trophoblast cells. Most importantly, bovine PL injection restored ß-cell proliferation and blood insulin concentrations in Adipoq -/- dams. Together, these results demonstrate that adiponectin plays a vital role in pregnancy-induced ß-cell proliferation by promoting PL expression in trophoblast cells.

Lignan Constituents from the Fruits of Viburnum macrocephalum f. keteleeri and Their α-Amylase, α-Glucosidase, and Protein Tyrosine Phosphatase 1B Inhibitory Activities.

Eight previously undescribed lignan glycosides, viburmacrosides A-H (1-8), and seven known analogues (9-15) were isolated from Viburnum macrocephalum f. keteleeri fruits through bioactivity-guided fractionation. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and chemical evidence. Using the well-recognized carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase, as well as the promising protein tyrosine phosphatase 1B (PTP1B), as inhibitory targets, all isolated compounds were tested for their antidiabetic potential in vitro. Compound 4 displayed potent inhibitory activities with IC50 values of 9.9 ± 0.6 and 8.9 ± 0.5 µM against α-glucosidase and PTP1B, respectively. The enzymatic kinetics results suggested that compound 4 competitively inhibited α-glucosidase while it suppressed α-amylase and PTP1B in the mixed-type manner. These findings supported that V. macrocephalum f. keteleeri fruits may be a new functional food resource with antidiabetic potential.

Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice.

To ensure fetal lipid supply, maternal blood triglyceride (TG) concentrations are robustly elevated during pregnancy. Interestingly, a lower increase in maternal blood TG concentrations has been observed in some obese mothers. We have shown that high-fat (HF) feeding during pregnancy significantly reduces maternal blood TG levels. Therefore, we performed this study to investigate if and how obesity alters maternal blood TG levels. Maternal obesity was established by prepregnant HF (ppHF) feeding, which avoided the dietary effect during pregnancy. We found not only that maternal blood TG concentrations in ppHF dams were remarkably lower than in control dams but also that the TG peak occurred earlier during gestation. Hepatic TG production and intestinal TG absorption were unchanged in ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased blood TG clearance contributes to the decreased blood TG concentrations in ppHF dams. Although significantly higher levels of UCP1 protein were observed in interscapular brown adipose tissue (iBAT) of ppHF dams, Ucp1 gene deletion did not restore blood TG concentrations in ppHF dams. Expression of the angiopoietin-like protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregnancy. However, the pregnancy-induced elevation of blood TG was almost abolished in Angptl4 -/- dams. Compared with control dams, Angptl4 mRNA levels were significantly lower in iBAT, gonadal white adipose tissue, and livers of ppHF dams. Importantly, ectopic overexpression of ANGPTL4 restored maternal blood TG concentrations in ppHF dams. Together, these results indicate that ANGPTL4 plays a vital role in increasing maternal blood TG concentrations during pregnancy. Obesity impairs the rise of maternal blood TG concentrations by reducing ANGPTL4 expression in mice.

Prolonged Prepregnant Maternal High-Fat Feeding Reduces Fetal and Neonatal Blood Glucose Concentrations by Enhancing Fetal ß-Cell Development in C57BL/6 Mice.

The main objective of this study was to investigate the effect of maternal obesity on offspring's glucose metabolism during the perinatal period. Maternal obesity was established by feeding C57BL/6 mice with a high-fat (HF) diet before or during pregnancy. Our results showed that prolonged prepregnant HF feeding but not HF feeding during pregnancy significantly reduced fetal and neonatal blood glucose concentrations. Remarkably, elevated blood insulin concentrations and increased activation of insulin signaling were observed in fetuses and neonates from prepregnant HF-fed dams. In addition, significantly larger ß-cell areas were observed in pancreases of fetuses and neonates from prepregnant HF-fed dams. Although there was no significant change in placental cross-sectional area or GLUT 1 expression, prepregnant HF feeding significantly enhanced the expression of genes that control placental fatty acid supply. Interestingly, reducing fatty acid supply to the placenta and fetus by placental-specific knockout of adipose triglyceride lipase not only reduced fetal ß-cell area and blood insulin concentration but also attenuated prepregnant HF feeding-induced reduction in offspring blood glucose concentrations during the perinatal period. Together, these results indicate that placental and fetal fatty acid supply plays an important role in fetal ß-cell development, insulin secretion, and glucose metabolism. Prolonged prepregnant maternal HF feeding resembles pregravid maternal obesity in mice, which reduces fetal and neonatal blood glucose concentrations by enhancing fetal ß-cell development and insulin secretion.

The platelet-derived growth factor receptor alpha promoter-directed expression of cre recombinase in mouse placenta.

BACKGROUND: Numerous pathologies of pregnancy originate from placental dysfunction. It is essential to understand the functions of key genes in the placenta in order to discern the etiology of placental pathologies. A paucity of animal models that allow conditional and inducible expression of a target gene in the placenta is a major limitation for studying placental development and function. RESULTS: To study the platelet-derived growth factor receptor alpha (PDGFRα)-directed and tamoxifen-induced Cre recombinase expression in the placenta, PDGFRα-CreER mice were crossed with mT/mG dual-fluorescent reporter mice. The expression of endogenous membrane-localized enhanced green fluorescent protein (mEGFP) and/or dTomato in the placenta was examined to identify PDGFRα promoter-directed Cre expression. Pregnant PDGFRα-CreER;mT/mG mice were treated with tamoxifen at various gestational ages. Upon tamoxifen treatment, reporter protein mEGFP was observed in the junctional zone (JZ) and chorionic plate (CP). Furthermore, a single dose of tamoxifen was sufficient to induce the recombination. CONCLUSIONS: PDGFRα-CreER expression is restricted to the JZ and CP of mouse placentas. PDGFRα-CreER mice provide a useful tool to conditionally knock out or overexpress a target gene in these regions of the mouse placenta.

High-fat feeding reprograms maternal energy metabolism and induces long-term postpartum obesity in mice.

BACKGROUND: Excessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity. METHODS: C57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery. RESULTS: We found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation. CONCLUSIONS: These results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT.

Chemical constituents and biological activities of Viburnum macrocephalum f. keteleeri.

Three new compounds (1-3) and seven known compounds (4-10) have been isolated from the ethanolic extract of Viburnum macrocephalum f. keteleeri using bioactivity-guided fractionation and identified as methyl (2-α-L-rhamnopyranosyloxy)acetate (1), methyl (2R-3-α-L-rhamnopyranosyloxy)glycerate (2), methyl (3R-4-α-L-rhamnopyranosyloxy-3-hydroxy)butanoate (3), bridelionoside B (4), (6S,7E,9R)-roseoside (5), linarionoside A (6), 3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol (7), (+)-8-hydroxylinalool (8), ß-sitosterol (9) and daucosterol (10). The structures of 1-3, including absolute configurations, were determined by spectroscopic data (1H and 13C NMR, HSQC, HMBC and ORD) and chemical methods. In addition, compounds 1-8 were assayed for their insecticidal and antimicrobial activities. Compounds 7 and 8 exhibited moderately insecticidal effects against Mythimna separata with LD50 values of 180 and 230 µg g-1, respectively. Compounds 2, 3, 7 and 8 showed varying antimicrobial activities with IC50 values ranging from 125 to 529 µM.