Synergistic effects of three traditional herbs green tea,mulberry leaf and corn silk on glucose uptake level of L6 myoblasts and the hypoglycemic mechanism

Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain unclear.Methods:The effective components of green tea,mulberry leaf and corn silk were extracted and enriched.Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts,so as to determine the optimal synergistic hypoglycemic combination.The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay,glucose uptake assay,and western blot.Results:Three polyphenol enrichment fractions of the herbs,30%ethanol elution fraction of green tea(GT),50%ethanol elution fraction of mulberry leaf(ML)and 60%ethanol elution fraction of corn silk(CS)were obtained.The antioxidant activities of GT-30%,ML-50%and CS-60%were superior to those of crude extracts,and showed strong potential inα-amylase andα-glucosidase inhibition activities.The optimal synergistic combination of crude extracts G7(crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk=1:5:3),polyphenol enrichment fractions R3(GT-30%:ML-50%:CS-60%=1:7:1)and monomers X2(epigallocatechin gallate:morusin:formononetin=3:1:2)were selected,respectively.G7,R3,and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range.In addition,G7,R3,and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts,and promote the translocation of Glut4,but G7 and R3 showed more significant effects.Conclusion:The synergistic hypoglycemic effects of green tea,mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K,p-Akt/Akt and the translocation of Glut4 signal pathways involved.The three traditional herbs might have the potential to be combined used for the prevention and treatment of diabetes based on the synergistic hypoglycemic effects.

Comparison of polysaccharides from 10 species of genera Paris,Trillium,Aspidistra,and Polygonatum

Background:The genera Paris,Trillium,Aspidistra,and Polygonatum originally belonged to the family Liliaceae;however,recently,in the APG system,the genera Polygonatum and Aspidistra were placed in the family Asparagaceae and the genera Paris and Trillium were placed in the family Melanthiaceae.Methods:To study the application of polysaccharide chemotaxonomy in Asparagaceae and Melanthiaceae,we extracted polysaccharides from the rhizomes of plants,including Paris polyphylla var.yunnanensis,Paris daliensis,Paris polyphylla var.chinensis,Trillium tschonoskii,Aspidistra elatior,Aspidistra sichuanensis,Aspidistra caespitosa,Polygonatum sibiricum,Polygonatum cyrtonema,and Polygonatum kingianum.Physicochemical and structural characterization of these polysaccharides was performed using molecular weight,monosaccharide composition,Fourier-transform infrared spectroscopy,nuclear magnetic resonance spectroscopy,and scanning electron microscopy.The immunomodulatory activities were evaluated using the macrophage cell line,RAW264.7.Results:In this study,we found that the polysaccharides from the genus Polygonatum and Aspidistra were mainly comprised of fructose and glucose;the molecular weights were mostly concentrated between 4.6-6.2 kDa.The polysaccharides from species of genus Polygonatum differed in that they contained acetyl groups,while polysaccharides from species of genus Aspidistra did not.Paris and Trillium species polysaccharides mainly consisted of glucose and mannose;the molecular weights of the two major peaks were 6.3-13 kDa and 1-1.5 kDa,respectively;the main differences between polysaccharides were the ratio of glucose and mannose and the degree of branching.These results suggest that fructans might be the main feature of the family Asparagaceae and fructans with acetyl groups might be the main feature of the genus Polygonatum which is consistent with the results of previous studies.Additionally,all polysaccharides from the 10 plants promoted phagocytic activity.Some of them exhibited strong activity,including nitrogen monoxide release and TNF-αsecretion by RAW264.7 macrophages,indicating that they could be used as potential immunomodulatory agents.Conclusion:The molecular weight distribution,monosaccharide composition,and surface morphology of the polysaccharides of the Polygonatum and Aspidistra plants were similar,while those of Paris and Trillium plants were similar.These results support the APG classification system,which placed the genera Polygonatum and Aspidistra in the Asparagaceae family and placed the genera Paris and Trillium in the Melanthiaceae family.

Evaluation of bioactive flavonoids in Citri Reticulatae Pericarpium from different regions and its association with antioxidant andα-glucosidase inhibitory activities

Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.

Preparation and characterization of resistant starch type 3 from yam and its effect on the gut microbiota

Background:Yam(Dioscorea opposita Thunb.)has been consumed as a food and used in traditional Chinese medicine for thousands of years.Resistant starch(RS)3 is of particular interest because it is heat-resistant,safe and non-toxic,and retains good nutritional benefits;it is therefore used in a wide range of traditional and emerging foods as a heat-stable prebiotic ingredient.In our previous study,we found that yam RS includes strong lipid-lowering and anti-constipation activities.Methods:Yam RS3 was prepared by autoclaving-retrogradation and pullulanase debranching to yield autoclaving-retrogradation yam RS and pullulanase debranching yam RS,respectively.First,the physicochemical properties of both RS3s were analyzed.Second,the structures of the RS3s were characterized by scanning electron microscopy,X-ray powder diffraction,and Fourier transform infrared spectroscopy.Finally,the regulatory effects of the RS3s on the gut microbiota were evaluated using an in vitro fecal fermentation model.Results:The RS content of the RS3s decreased after processing,but was higher in pullulanase debranching yam RS(35.67%)than in autoclaving-retrogradation yam RS(28.71%).Compared with native yam starch,RS3s lost their original granular shapes and instead exhibited irregularly shapes with continuous phases.The crystalline structure of the RS3s was completely altered,with pullulanase debranching yam RS exhibiting B-type patterns.Both RS3s,and especially pullulanase debranching yam RS,promoted a significant increase in short chain fatty acid content after in vitro fermentation(all P<0.05).Moreover,pullulanase debranching yam RS significantly increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria such as Escherichia and Shigella(all P<0.05).Conclusion:Our findings show that yam RS3s can regulate the composition of the gut microbiota and promote the production of short chain fatty acid,especially butyric acid.Pullulanase debranching was a more effective method for producing functional yam RS3.

Quality evaluation of Pinelliae Rhizoma using network pharmacology and multi-component quantitative analysis

Background:Pinelliae Rhizoma(Banxia)is a valuable traditional Chinese medicine,and its quality issues are related to the safety and effectiveness of the medicine.Several pharmacological experiments have shown that Pinelliae Rhizoma has anti-inflammatory activity,but the specific chemical components remain unclear.Methods:In the present study,network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of Pinelliae Rhizoma’s anti-inflammatory activity.A new approach to simultaneously determine eight components using high performance liquid chromatography-photo-diode array was developed to evaluate the quality of Pinelliae Rhizoma and different processed Pinelliae Rhizoma products.Results:Twelve active ingredients were identified from Pinelliae Rhizoma,andβ-sitosterol may have a greater effect than the other active ingredients.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the main pathways associated with Pinelliae Rhizoma’s mechanism for treating inflammation.Additionally,theβ-sitosterol content in different processed Pinelliae Rhizoma products decreased significantly,and the level of five nucleosides in Pinelliae Rhizoma was significantly higher than that of the processed Pinelliae Rhizoma products.The 6-gingerol content was detected in eight Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine batches with different origins,and liquiritin and liquiritigenin levels were detected in eight batches of Pinelliae Rhizoma Praeparatum with different origins.Conclusion:Pinelliae Rhizoma quality was affected by different regions and different processing methods,and this research provides a reference for Pinelliae Rhizoma quality evaluation.

Gut liver brain axis in diseases:the implications for therapeutic interventions

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

Chemical composition,pharmacological activity and development strategies of Rubus chingii:A review

Raspberries are used for both food and medicine,but it has not yet attracted widespread attention.In this paper,the chemical constituen of the original plant raspberry.R.chingii is one of the new“Zhe Bawei”medicinal materials selected in 2017.“Zhe Bawei”refers to eight kinds of genuine medicinal materials in Zhejiang Province.The chemical constituents,pharmacological effects,processing,and application of Rubus chingii Hu were reviewed to provide a reference for its further development.Relevant literature in recent years was collected in databases such as China Knowledge Network,Web of Science,Elsevier,PubMed,and X-Mol,using“raspberry”,“Rubus chingii”,“traditional use”,“chemical composition”,“pharmacology”,etc.as keywords individually or in combination.The summary of pharmacological activities shows that the relationship between the pharmacological activities of raspberry is still not deep enough.More in-depth research should be carried out in this direction to explore the mechanism of action of its active ingredients and provide effective reference for the further development of the raspberry industry.In the future,with the participation of more researchers,it is expected to develop innovative drugs based on raspberry for the treatment of diseases.

Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China

Objective:Pseudostellaria heterophylla has been paid more attention in recent years,mainly as a medicine food homology plant.The content determination of P.heterophylla is not specified in the Chinese Pharmacopoeia(version 2020).The environmental conditions in different production areas could exert an influence on the quality of P.heterophylla.The purpose of this study is to discriminate P.heterophylla collected from different geographical origins of China.Methods:In this study,the content of polysaccharide in 28 batches of P.heterophylla was determined using phenol–sulfuric acid.HPLC fingerprints were established under optimised HPLC-PDA methods.Subsequently,the similarity analysis(SA)and the quantification of heterophyllin B were analyzed.The metabolites of P.heterophylla were identified and evaluated using UHPLC-Q Exactive HF orbitrap MS system.Principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA),hierarchical cluster analysis(HCA)and orthogonal PLS-DA(OPLS-DA)were performed based on all peak areas.Results:The polysaccharide content in Guizhou and Jiangsu was higher than that of other production areas,which varied significant from different origins.While the content of heterophyllin B in Anhui and Jiangsu was high.The correlation coefficients of HPLC fingerprints for 28 batches samples ranged from 0.877 to 0.990,and the characteristic map can be used to identify and evaluate the quality of P.heterophylla.The samples from Fujian,Guizhou,Jiangsu provinces can be relatively separated using multivariate statistical analysis including PCA,PLS-DA,HCA,OPLS-DA,indicating that their metabolic compositions were significantly different.Ultimately,a total of 15 metabolites which were filtrated by a VIPvalue>1 and a P-value<0.05 associated with the separation of different origins were identified.Conclusion:HPLC fingerprint was established to evaluate the quality and authenticity of P.heterophylla.The present work showed that the difference of geographic distributions had an influence on the internal chemical compositions.A sensitive and rapid untargeted metabolomics approach by UHPLC-Q Exactive HF orbitrap MS was utilized to evaluate P.heterophylla from different origins in China for the first time.Overall,this study provides insights to metabolomics of P.heterophylla and supplies important reference values for the development of functional foods.

Recent progress in the structural study of ion channels as insecticide targets

Ion channels,many expressed in insect neural and muscular systems,have drawn huge attention as primary targets of insecticides.With the recent technical breakthroughs in structural biology,especially in cryo-electron microscopy(cryo-EM),many new high-resolution structures of ion channel targets,apo or in complex with insecticides,have been solved,shedding light on the molecular mechanism of action of the insecticides and resistance mutations.These structures also provide accurate templates for structure-based insecticide screening and rational design.This review summarizes the recent progress in the structural studies of 5 ion channel families:the ryanodine receptor(RyR),the nicotinic acetylcholine receptor(nAChR),the voltage-gated sodium channel(VGSC),the transient receptor potential(TRP)channel,and the ligand-gated chloride channel(LGCC).We address the selectivity of the channel-targeting insecticides by examining the conservation of key coordinating residues revealed by the structures.The possible resistance mechanisms are proposed based on the locations of the identified resistance mutations on the 3D structures of the target channels and their impacts on the binding of insecticides.Finally,we discuss how to develop“green”insecticides with a novel mode of action based on these high-resolution structures to overcome the resistance.

Synthesis of 3-Methylthio-benzo[b]furans/Thiophenes via Intramolecular Cyclization of 2-Alkynylanisoles/Sulfides Mediated by DMSO/DMSO-d_(6) and SOCl_(2)

Main observation and conclusion The reaction of 2-alkynylanisoles/sulfides with SOCl_(2) and DMSO was conducted to conveniently furnish the biologically interesting 3-(methylthio)-benzo[b]furans/thiophenes via intramolecular cyclization.DMSO acts as a solvent as well as a sulfur source and can also be replaced with DMSO-d_(6),enabling the incorporation of the SCD3 moiety of DMSO-d_(6) to the 3-position of the heterocyclic frameworks.

Synthesis of 3-Methylthioindoles via Intramolecular Cyclization of 2-Alkynylanilines Mediated by DMSO/DA/lSO-d_(6) and SOCI_(2)

The intramolecular cyclization of 2-alkynylanilines mediated by DMSO/SOCI_(2) was found to afford biologically interesting 3-methylthioindoles,which are rarely obtained by the exiting methods.DMSO could also be replaced with its deuterated counterpart,enabling the method applicable to the construction of indole skeleton bearing a SCD_(3) moiety at its 3-position.

PhlCl_(2)/NH_(4)SCN-Mediated Oxidative Regioselective Thiocyanation of Pyridin-2(1H)-ones

The reaction of pyridin-2(1H)·ones with PhlCl_(2) and NH_(4)SCN enables an efficient regioselective thiocyanation,leading to the synthesis of the biologically interesting C5 thiocyanated 2-pyridones in good to high yields.The mechanistic pathway of this metal-free approach is postulated to involve the formation of the reactive thiocyanogen chloride from the reaction of PhlCl_(2) and NH4SCN followed with the regioselective electrophilic thiocyanation of the pyridin-2(1H)-one ring.

Synthesis of 3-thiocyanated chromones via TCCA/NH_(4)SCN-mediated cyclization/thiocyanation of alkynyl aryl ketones

3-Thiocyanated chromones was conveniently synthesized from alkynyl aryl ketones using commercially available,inexpensive trichloroisocyanuric acid(TCCA)as oxidant and NH_(4)SCN as thiocyanato(SCN)source.This metalfree approach is postulated to first in situ generate thiocyanogen chloride(Cl-SCN)from the reaction of TCCA and NH_(4)SCN,followed by a rare efficient electrophilic thiocyano oxyfunctionalization of alkynes enabled by the reactive electrophilic species generated thereof.