[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the...[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.展开更多
The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate i...The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.展开更多
Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was succes...Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.展开更多
Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we pro...Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.展开更多
The title complex, {[Cu2(4,4'-bipyridine)2(μ-O2CMe)2(O2CMe)2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474...The title complex, {[Cu2(4,4'-bipyridine)2(μ-O2CMe)2(O2CMe)2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474(5), b = 11.7566(2), c = 19.5380(6)A, β = 92.930(2)°, V = 3084.84(16) A^3, Z = 4, Cu2C28N409H30, Mr = 693.64, Dc = 1.494 g/cm^3, F(000) = 1424 and μ(MoKα) = 1.436 mm^-1. With the use of 2062 observed reflections (I 〉 2σ(I)), the structure was refined to R = 0.0769 and wR = 0.2154. In complex 1, the dimeric copper acetate units are linked through 4,4’-bipyridine to yield ID molecular ladders. These ladders are connected via O-H…O hydrogen bonds to generate 2D layers, which are further linked through C-H…O hydrogen bonds to give a 3D supramolecular network.展开更多
A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can ...A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can be trapped and moved (transported) dynamically within the wavelength router and bus networks, in which the required drug delivery can perform within the wavelength router before reaching the required destination. PANDA ring is a modified optical add/drop filter. It is a name of Chinese bear, which is used to name the device by the authors. The advantage of the proposed system is that the drug delivery networks can perform within the tiny system (thin film device), where the large molecular drug networks such as ring, star and bus networks are also proposed, in which the applications such as Alzheimers’ and Parkinson diagnosis, blood circulation networks and in situ surgery operation are discussed.展开更多
The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compound...The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.展开更多
Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underl...Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.展开更多
Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,...Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.展开更多
Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy....Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.展开更多
Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide...Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. Results: In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. Conclusions: The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of hiomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.展开更多
Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AC...Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around China.Their bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/ml.Six strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum TBG1-17.From the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH incubation.Furthermore,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone I.aspernolide E,a phenolic derivative and possibly unknown compounds 8-10 and 12.展开更多
Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsilliti...Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,pneumonia.The current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in V.amygdalina.First,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes.Furthermore,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this plant.Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V.amygdalina leaf.展开更多
Identification of human immunodeficiency virus(HIV)transmission networks is a critical step in the public health response;however,it is challenging to achieve this through traditional epidemiological surveys alone.The...Identification of human immunodeficiency virus(HIV)transmission networks is a critical step in the public health response;however,it is challenging to achieve this through traditional epidemiological surveys alone.The molecular network approach can provide more accurate information for understanding HIV outbreaks and bring targeted interventions into reality.Based on the current global development of the concept of the molecular network,Chinese scientists have in recent years explored the applications of molecular networks for understanding the HIV-1 transmission trends,for identifying the population acquiring priority interventions,and for evaluating the targeted intervention effectiveness.In this review,we focus on research progress by Chinese scientists in the field of molecular networks and put forward some suggestions for future research of molecular networks.展开更多
In this review a series of organic-based open porous networks are discussed, in which hydrogen bonds play an important role in network formation. Using these open networks as molecular templates: 1) a wealth of functi...In this review a series of organic-based open porous networks are discussed, in which hydrogen bonds play an important role in network formation. Using these open networks as molecular templates: 1) a wealth of functional guest species can be immo- bilized; 2) fullerene molecules can be separated and recognized; 3) photoisomerization reactions can be observed by STM; 4) 1D molecular arrays can be constructed; and 5) heterogeneous bilayer structures can be formed. It is envisioned that these su- pramolecular networks might be developed into a new family of useful soft frameworks for studies toward shape-selective ca- talysis, molecular recognition and host-guest supramolecular chemistry.展开更多
Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply ...Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the展开更多
The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmac...The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ·mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.展开更多
基金Supported by Guizhou Provincial Science and Technology(ZK(2022)-362,ZK(2024)-047,[2023]ZK01)The Innovation and Entrepreneurship Training Program for Undergraduates from China[202210660131,202310660082]+2 种基金Science Foundation of Guizhou Education Technology(2022-064)University Engineering Research Center for the Prevention and Treatment of Chronic Diseases by Authentic Medicinal Materials in Guizhou Province([2023]035)Science and Technology Research Project of Guizhou Administration of Traditional Chinese Medicine(QZYY-2024-134).
文摘[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.
基金The National Natural Science Foundation of China under contract Nos 22264003,42090041 and 42030502the Guangxi Natural Science Fund Project under contract Nos AD17129063,AA17204074 and 2018GXNSFAA281354the Innovation and Entrepreneurship Training Program of College Students from Guangxi University under contract Nos 202210593888 and202210593890。
文摘The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine(Grant No.CBCM2020104).
文摘Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.
基金financially supported by the National Key R&D Program of China(Grant No.:2018YFC1704502)the National Natural Science Foundation of China(Grant No.:81603268)the National Natural Science Foundation of China(Grant No.:81822047)
文摘Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.
基金This work was supported by the Science Foundation of Fujian Provincial Key Laboratory of Polymer Materials
文摘The title complex, {[Cu2(4,4'-bipyridine)2(μ-O2CMe)2(O2CMe)2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474(5), b = 11.7566(2), c = 19.5380(6)A, β = 92.930(2)°, V = 3084.84(16) A^3, Z = 4, Cu2C28N409H30, Mr = 693.64, Dc = 1.494 g/cm^3, F(000) = 1424 and μ(MoKα) = 1.436 mm^-1. With the use of 2062 observed reflections (I 〉 2σ(I)), the structure was refined to R = 0.0769 and wR = 0.2154. In complex 1, the dimeric copper acetate units are linked through 4,4’-bipyridine to yield ID molecular ladders. These ladders are connected via O-H…O hydrogen bonds to generate 2D layers, which are further linked through C-H…O hydrogen bonds to give a 3D supramolecular network.
文摘A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can be trapped and moved (transported) dynamically within the wavelength router and bus networks, in which the required drug delivery can perform within the wavelength router before reaching the required destination. PANDA ring is a modified optical add/drop filter. It is a name of Chinese bear, which is used to name the device by the authors. The advantage of the proposed system is that the drug delivery networks can perform within the tiny system (thin film device), where the large molecular drug networks such as ring, star and bus networks are also proposed, in which the applications such as Alzheimers’ and Parkinson diagnosis, blood circulation networks and in situ surgery operation are discussed.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120066 and 2022A1515010010)the National Natural Science Foundation of China[Nos.82293681(82293680)and 82273822]+3 种基金the Science and Technology Key Project of Guangdong Province(No.2020B1111110004)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Fundamental Research Funds for the Central Universitiesthe support of K.C.Wong Education Foundation。
文摘The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.
文摘Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.
基金This work was supported by the Program of National Natural Science Foundation of China(Nos.41906090,81874300,42006092,U1706210,41776141 and 41322037)the Program of Natural Science Foundation of Shandong Province of China(Nos.JQ201510 and ZR2019BD047)+1 种基金Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education,Hainan Normal University(RDZH2021003)the Taishan Scholars Program,China(No.tsqn20161010).
文摘Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.
基金Financial support for this study is from the"Double First-Class"University project(CPU2018GY08,China)the 111 Project from Ministry of Education of China and the State Administration of Foreign Export Affairs of China(B18056)the National New Drug Innovation Major Project(2018ZX09711-001-007).
文摘Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.
基金This work was partly supported by the National Nature Science Foundation of China (Nos. 91530321, 61390513, 61602347 and 61572363), and the Fundamental Research Funds for the Central Universities.
文摘Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. Results: In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. Conclusions: The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of hiomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.
基金This work was supported by the Yangfan Talent Project of Guangdong Province under Grant 201433009the Natural Science Foundation of Guangdong Province under Grant 2018A030307046+7 种基金the Basic Research Project of Shenzhen Science and Technology Innovation Commission under Grant JCYJ20190813105005619the Shenzhen Dapeng New District Industrial Development Fund under Grants KY20180203&PT201901-05the Shenzhen Dapeng New District Scientific and Technological Research and Development Fund under Grant KJYF202001-07the Natural Science Foundation of China under Grant 21807015the Program for Scientific Research Start-Up Funds of Guangdong Ocean University under Grant E15155the Applied S&T Research and Development Major Project of Guangdong Province under Grant 2016B020235001the Scientific Fund of the Zhanjiang Municipal Oceanic and Fishery Bureau under Grant A18018the Project of Enhancing School with Innovation of Guangdong Ocean University(230420022).
文摘Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around China.Their bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/ml.Six strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum TBG1-17.From the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH incubation.Furthermore,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone I.aspernolide E,a phenolic derivative and possibly unknown compounds 8-10 and 12.
基金supported by the National Natural Science Foundation of China(No.81573550)。
文摘Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,pneumonia.The current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in V.amygdalina.First,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes.Furthermore,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this plant.Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V.amygdalina leaf.
基金This work was supported by Mega-Projects of National Science Research for the 13th Five-Year Plan(2018ZX10721102)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-027)。
文摘Identification of human immunodeficiency virus(HIV)transmission networks is a critical step in the public health response;however,it is challenging to achieve this through traditional epidemiological surveys alone.The molecular network approach can provide more accurate information for understanding HIV outbreaks and bring targeted interventions into reality.Based on the current global development of the concept of the molecular network,Chinese scientists have in recent years explored the applications of molecular networks for understanding the HIV-1 transmission trends,for identifying the population acquiring priority interventions,and for evaluating the targeted intervention effectiveness.In this review,we focus on research progress by Chinese scientists in the field of molecular networks and put forward some suggestions for future research of molecular networks.
文摘In this review a series of organic-based open porous networks are discussed, in which hydrogen bonds play an important role in network formation. Using these open networks as molecular templates: 1) a wealth of functional guest species can be immo- bilized; 2) fullerene molecules can be separated and recognized; 3) photoisomerization reactions can be observed by STM; 4) 1D molecular arrays can be constructed; and 5) heterogeneous bilayer structures can be formed. It is envisioned that these su- pramolecular networks might be developed into a new family of useful soft frameworks for studies toward shape-selective ca- talysis, molecular recognition and host-guest supramolecular chemistry.
基金financially supported by 1226 major project [Grant no.AWS16J018]
文摘Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the
文摘The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ·mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.