BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The...BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.展开更多
Objective:Coronavirus disease-2019(COVID-19)can cause not only respiratory symptoms but also facial paralysis.Lianhua Qingwen(LHQW)has been reported to have therapeutic effects on COVID-19 and facial neuritis(FN).We e...Objective:Coronavirus disease-2019(COVID-19)can cause not only respiratory symptoms but also facial paralysis.Lianhua Qingwen(LHQW)has been reported to have therapeutic effects on COVID-19 and facial neuritis(FN).We explored the potential mechanism of LHQW in the treatment of COVID-19 and FN through a network-pharmacology approach.Methods:Active compounds and relevant targets of LHQW were obtained from the databases of Traditional Chinese Medicine Systems Pharmacology Database,HERB,UniProt Knowledge Base,SwissADME,and Swiss Target Prediction.Disease targets of COVID-19 and FN were acquired from Gene Cards.Database For Annotation,Visualization And Integrated Discovery and Metascape were used to search the biological functions of intersecting targets.After identifying the core targets and their corresponding ingredients,KEGG Mapper analyzes the localization of core targets in key pathways.AutoDock were employed to conduct molecular docking of the core targets and their corresponding ingredients.Results:We obtained four core genes:interleukin(IL)-8,IL-1B,IL-6,and tumor necrosis factor(TNF)-α.Database searching revealed the anti-inflammatory and antiviral effects of LHQW may be related to the action of aleo-emodin,hyperforin,kaempferol,luteolin,and quercetin on these four genes by regulating the pathways of IL-17 and NOD-like receptor.The molecular-docking results of the four core targets and their corresponding active ingredients showed good binding activity between receptors and ligands.Conclusions:We uncovered the active ingredients,potential targets,and biological pathways of LHQW for COVID-19 and FN coinfection.Our data provide a theoretical basis for further exploration of the mechanism of action of LHQW in treatment of COVID-19 and FN.展开更多
Natural products,the most important chemical library with magical structures and unique functions,have long been playing significant roles in contributing to the discovery of novel drugs.The complexity and diversity o...Natural products,the most important chemical library with magical structures and unique functions,have long been playing significant roles in contributing to the discovery of novel drugs.The complexity and diversity of natural products present great challenges regarding the exploration of their potential targets.Identifying the targets of natural products not only enhances our understanding of biological functions and molecular mechanisms,but also paves the way for discovering novel lead compounds for disease treatment.Recent advances in technologies like chemical biology,structural biology,and artificial intelligence have provided powerful tools for pinpointing natural product target and unraveling molecular mechanisms.This review aims to comprehensively summarize the innovative strategies employed in recent years to identify natural product targets,and evaluate their impact on biological pathways by modulating target functions for pharmacological effects.Moreover,we also discuss the challenges encountered in this field and outline future research prospects,aiming to offer guidance for researchers in natural product chemical biology.展开更多
Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal ...Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal medications,such as loperamide and octreotide,is relatively limited because of their unsatisfactory efficacy and adverse effects.In recent years,traditional Chinese medicine(TCM)has attracted great interest because of its beneficial effect in treating CID,which has multitarget and low-toxicity therapeutic characteristics.TCM exhibits remarkable therapeutic potential in the prevention and treatment of CID.It can alleviate and treat CID by regulating chemical drug metabolism,improving the integrity of the intestinal barrier,stimulating proliferation while suppressing the apoptosis of intestinal epithelial cells,ameliorating oxidative stress and inflammation and regulating bile acids and aquaporins.However,large-scale,randomized,double-blind clinical trials of TCM for the treatment of CID are lacking,and most preclinical experiments have not been translated to clinical trials.Accordingly,this review highlights the clinical efficacy and molecular mechanisms of TCM against CID via PubMed,Web of Science and China National Knowledge Infrastructure and proposes that future research on TCM against CID should focus on strengthening the connection from bench to bed,which may help to comprehensively evaluate the therapeutic potential of TCM against CID.展开更多
Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapie...Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.展开更多
When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifung...When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifungal drugs available for clinical use are limited,and their toxicity and safety issues can lead to adverse effects for patients.The emergence of drug-resistant strains and the“super fungus”Candida auris has further complicated treatment.Consequently,the identification of new antifungal medications and the formulation of effective combination therapy strategies have emerged as pivotal research priorities within this discipline.Natural products are specialized small molecules that are produced in nature and play pivotal roles in numerous cellular processes and are considered to be among the most significant pharmaceutical agents in the field of human healthcare.Accordingly,the objective of this paper is to review natural products and relevant compounds that exhibit antifungal activity by targeting key components of the fungal cell walls or cell membranes.We focused on the most recent research findings from 2022 to 2025 concerning antifungal natural products derived from plants,fungi,and bacteria,and conducted a comprehensive summary of the sources and types of natural products,along with their antifungal mechanisms of action.Furthermore,we analyzed the application prospects of combining novel natural products with existing antifungal drugs from the perspective of compensatory mechanisms of fungal cell structures,thus establishing new treatment strategies for fungal infections.展开更多
Gualou-Xiebai-Banxia Decoction(GXBD)is a traditional Chinese herbal formula including four traditional Chinese medicines:Gualou(Trichosanthis Fructus,TF),Xiebai(Allii Macrostemonis Bulbus,AMB),Banxia(Pinelliae Rhizoma...Gualou-Xiebai-Banxia Decoction(GXBD)is a traditional Chinese herbal formula including four traditional Chinese medicines:Gualou(Trichosanthis Fructus,TF),Xiebai(Allii Macrostemonis Bulbus,AMB),Banxia(Pinelliae Rhizoma,PR)and yellow wine.It is a classical therapy for chest stuffiness and pain syndrome and is widely used in the clinical treatment of coronary heart disease.It also shows significant therapeutic effects on pulmonary heart disease,hyperlipidemia,and arrhythmia.This study conducted a literature review and collected information on GXBD from databases such as PubMed,Web of Science,China National Knowledge Infrastructure,and ScienceDirect.The result indicated that the main active ingredients of GXBD are steroids,flavonoids,terpenoids,alkaloids,amino acids,and organic acids.Trigonelline,macrostemonoside and cucurbitacin B can provide reference for its quality control.GXBD may exert therapeutic effects on coronary heart disease through AMPK,PI3K-AKT,oxLDL,VEGF,and NF-κB signal pathways.This review provides a comprehensive analysis and summary of the chemical composition and in vivo metabolism of three traditional Chinese medicines(TF,AMB,and PR),along with an evaluation of the chemical composition,quality control,pharmacological effects,and clinical application of GXBD.Based on these,areas requiring further research on GXBD have been proposed to provide a reference for its further development and new drug research.展开更多
Pulmonary hypertension(PH)is a pulmonary vascular disease caused by multiple etiologies,characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure,which can lead to severe cardiova...Pulmonary hypertension(PH)is a pulmonary vascular disease caused by multiple etiologies,characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure,which can lead to severe cardiovascular complications.The third type of PH,hypoxic pulmonary hypertension(HPH)caused by chronic lung disease and/or hypoxia,has complex and incomplete pathological mechanism.Current clinical treatment for HPH primarily focus on alleviating symptoms,with limited effectiveness in improving pulmonary vascular remodeling(PVR).Recent studies by various scholars have indicated that certain traditional Chinese medicine(TCM)monomers,extracts,and formulations can inhibit multiple signaling pathways,thereby suppressing pulmonary vascular remodeling and demonstrating favorable efficacy against HPH.This article reviews the pathogenesis of HPH,including pulmonary arterial wall thickening,immune inflammation,and thrombogenesis,and discusses the latest research advancements regarding the pharmacodynamic mechanisms of TCM in treating HPH.展开更多
Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here...Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)reuptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antidepressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protection,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor receptor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.展开更多
Background:Alzheimer’s disease(AD)is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment.Traditional herbal medicines may be helpful in the discovery of new anti-A...Background:Alzheimer’s disease(AD)is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment.Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs.Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects,which may be beneficial for the treatment of AD.However,the combination of active ingredients and their mechanisms remain unclear.Therefore,we aimed to identify potential active ingredients in F.assafoetida and their mechanisms of action against AD by using network pharmacology.Methods:In our study,an integrated network pharmacological approach,that included adsorption,distribution,metabolism and excretion screening,target identification,network construction,topological analysis,gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,and molecular docking,was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD.Results:The results indicated that 12 key active ingredients,obtained by topological analysis(including farnesiferol a,conferol,farnesiferol b,ferulic acid,etc.),may be the primary pharmacological components that may ameliorate AD.The 2 key significant pathways identified are the cholinergic synapse signaling pathway(critical targets include ACHE,CHRM1,CHRM2,MAPK1,PIK3CA,PIK3CB,PIK3CD,and PIK3CG)and the AD signaling pathway(critical targets include APP,BACE1,GSK3B,MAPK1,NCSTN,NOS1,PSEN1).These critical targets are closely related to the regulation of three typical pathological features of AD[central nervous system(CNS)cholinergic hypofunction,amyloid-β(Aβ)plaques,and hyperphosphorylated tau proteins].Finally,14 critical targets in the 2 key significant pathways were validated by molecular docking analysis.Conclusion:F.assafoetida may be effective for alleviating AD symptoms,through multi-component,multi-target,and multi-pathway synergistic effects,associated with the multiple pathogenesis hypotheses of AD.Our study may provide certain clues for the further development and utilization of this natural herbal medicine.展开更多
Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many ...Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.展开更多
Objective:To investigate the possible molecular mechanism of panax notoginseng in the treatment of vitreous hemorrhage(VH).Methods:The active components of Panax notoginseng were screened by TCMSP database and the cor...Objective:To investigate the possible molecular mechanism of panax notoginseng in the treatment of vitreous hemorrhage(VH).Methods:The active components of Panax notoginseng were screened by TCMSP database and the corresponding targets were collected.Vh-related gene targets were derived from GeneCards and OMIM database,and the target of Panax notoginseng was mapped to disease target genes.STRING database and Cytoscape 3.7.2 software were used to construct the protein-protein interaction(PPI)network diagram and the interaction network of"Pantoginseng-active ingredient-VH-target protein",and the core action target genes were screened out.Finally,gene body(GO)biological process and metabolic pathway enrichment analysis of KEGG were performed on the potential therapeutic targets.Results:We identified 8 active components,162 active component targets,1387 VHrelated genes and 75 candidate targets for VH.In the"Panax notoginseng-active ingredient-VH-target protein"interaction network,there are 82 nodes in total.The core target genes include AKT1,CASP3,VEGF-A,IL-6 and MMP-9.143 major enrichment pathways were identified by GO and KEGG enrichment analysis.The key signal pathways include age-RAGE signaling pathway,fluid shear stress and atherosclerosis,etc.,and the significant molecular functions include cytokine activity,receptor ligand activity,cytokine receptor binding,etc.Conclusion:The potential molecular mechanism of panax notoquinone in the treatment of VH is closely related to the biological processes of anti-angiogenesis,anti-inflammation,regulation of apoptosis and oxidative stress,and AKT1,CASP3,VEGF-A,IL-6 and MMP-9 may be the core target genes.展开更多
Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic...Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.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
Background:This study aimed to identify the main active components,targets and pathways of Yueju pill,explore its mechanism in the treatment of depressive polycystic ovary syndrome,so as to provide proofs for expandin...Background:This study aimed to identify the main active components,targets and pathways of Yueju pill,explore its mechanism in the treatment of depressive polycystic ovary syndrome,so as to provide proofs for expanding the clinical application of Yueju pill.Methods:The active components and targets of Yueju pill were retrieved from the traditional Chinese medicine system pharmacology(TCMSP)database and analysis platform.GeneCards and OMIM were used to search the disease targets of polycystic ovary syndrome and depression.The intersection genes of drug and disease were obtained via venny.R.STRING 11.0 was adopted to construct PPI network,then we obtained the hub genes with count.R.Utilized Cytoscape 3.7.2 to construct the"drug-disease-active ingredientsproteins"network.Finally,the Bioconductor tools of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were applied to the enrichment of biological functions and pathways.Results:There were 37 compounds in the prescription of Yueju pill,and 83 intersection genes of Yueju pill and PCOS-Depression.The significant genes were IL6,VEGFA,EGF,MAPK1,ESR1,MAPK8,EGFR and MAPK14.Through the enrichment of GO and KEGG,we found 106 biological processes and 129 signaling pathways were related to the treatment of depressive polycystic ovary syndrome with Yueju pill.Conclusions:Our study could provide sufficient data in supporting Yueju pill to treat polycystic ovary syndrome,while the purpose of anti-depression should be achieved by relieving the systemic symptoms.This study would provide fresh insights for expanding the clinical application of Yueju pill.展开更多
The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atheroscleros...The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atherosclerosis.Recent studies have elucidated the interaction between natural medicines and this co-metabolism system.Upon oral administration,natural medicine ingredients can undergo transformation by gut microbiota,potentially enhancing their bioavailability or anti-atherogenic efficacy.Furthermore,natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism.This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites.It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines’intervention on key nodes of endogenous host-microbe co-metabolism.These insights may offer new perspectives for cardiovascular disease(CVD)treatment and guide future drug discovery efforts.展开更多
Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier...This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune condition that leads to chronic arthritis,disability,and reduced lifespan.Current therapies show limited effectiveness and often cause severe side effects,with up to 50...Rheumatoid arthritis(RA)is a systemic autoimmune condition that leads to chronic arthritis,disability,and reduced lifespan.Current therapies show limited effectiveness and often cause severe side effects,with up to 50%of patients discontinuing disease-modifying antirheumatic drugs(DMARDs)due to unsatisfactory outcomes.Natural bioactive compounds(NBCs),such as glycosides,alkaloids,terpenoids,flavonoids,polyphenols,and coumarins,have gained attention for their immunomodulatory and antiinflammatory properties.However,challenges like poor solubility,high dosage requirements,short action duration,and low tissue specificity hinder their clinical use.Nanoparticle(NP)-based delivery systems,including lipid NPs(LNPs),polymer carriers,and inorganic nanocarriers,have been designed to address these challenges through passive,active,and stimuli-responsive strategies.NBC-loaded NPs target immune dysfunction,synovial hyperplasia,bone destruction,angiogenesis,inflammation,and oxidative stress(OS)in RA.This article highlights recent advancements in NBCs for RA treatment,nanoformulation design,and targeted mechanisms,while addressing challenges and future directions in this field.The integration of cutting-edge nanotechnology has demonstrated significant potential to overcome traditional barriers such as low bioavailability and off-target effects through intelligent NPs design.Future research should enhance artificial intelligence(AI)-driven modeling to predict drugnanocarrier interactions,develop biomarker frameworks for precision nanomedicine,and optimize RA management.展开更多
Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to G...Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.展开更多
基金Supported by the Xiangshan Talented Scientific Research Project of Zhuhai People’s Hospital,No.2021XSYC-02Research Start Project of Zhuhai People’s Hospital,No.2020ycqd001.
文摘BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.
基金funded by Natural Science Foundation of Shandong Province(ZR2021MH378)Natural Science Foundation of Shandong Province(ZR2022QH073).
文摘Objective:Coronavirus disease-2019(COVID-19)can cause not only respiratory symptoms but also facial paralysis.Lianhua Qingwen(LHQW)has been reported to have therapeutic effects on COVID-19 and facial neuritis(FN).We explored the potential mechanism of LHQW in the treatment of COVID-19 and FN through a network-pharmacology approach.Methods:Active compounds and relevant targets of LHQW were obtained from the databases of Traditional Chinese Medicine Systems Pharmacology Database,HERB,UniProt Knowledge Base,SwissADME,and Swiss Target Prediction.Disease targets of COVID-19 and FN were acquired from Gene Cards.Database For Annotation,Visualization And Integrated Discovery and Metascape were used to search the biological functions of intersecting targets.After identifying the core targets and their corresponding ingredients,KEGG Mapper analyzes the localization of core targets in key pathways.AutoDock were employed to conduct molecular docking of the core targets and their corresponding ingredients.Results:We obtained four core genes:interleukin(IL)-8,IL-1B,IL-6,and tumor necrosis factor(TNF)-α.Database searching revealed the anti-inflammatory and antiviral effects of LHQW may be related to the action of aleo-emodin,hyperforin,kaempferol,luteolin,and quercetin on these four genes by regulating the pathways of IL-17 and NOD-like receptor.The molecular-docking results of the four core targets and their corresponding active ingredients showed good binding activity between receptors and ligands.Conclusions:We uncovered the active ingredients,potential targets,and biological pathways of LHQW for COVID-19 and FN coinfection.Our data provide a theoretical basis for further exploration of the mechanism of action of LHQW in treatment of COVID-19 and FN.
基金supported by National Natural Sciences Foundation of China(82325050,U23A20529,82174008,82204678)Beijing Municipal Natural Science Foundation(7232273,7222265)+1 种基金Special Fund for“Tian-Chi Talent Introduction Program”Special Fund for Taishan Scholars Project in Shandong Province(tstp20230633)。
文摘Natural products,the most important chemical library with magical structures and unique functions,have long been playing significant roles in contributing to the discovery of novel drugs.The complexity and diversity of natural products present great challenges regarding the exploration of their potential targets.Identifying the targets of natural products not only enhances our understanding of biological functions and molecular mechanisms,but also paves the way for discovering novel lead compounds for disease treatment.Recent advances in technologies like chemical biology,structural biology,and artificial intelligence have provided powerful tools for pinpointing natural product target and unraveling molecular mechanisms.This review aims to comprehensively summarize the innovative strategies employed in recent years to identify natural product targets,and evaluate their impact on biological pathways by modulating target functions for pharmacological effects.Moreover,we also discuss the challenges encountered in this field and outline future research prospects,aiming to offer guidance for researchers in natural product chemical biology.
基金supported by the Innovative Team Project of Ordinary Universities in Guangdong Province(No.2022KCXTD016).
文摘Chemotherapy-induced diarrhea(CID)is a major concern for cancer patients and is associated with significant morbidity and mortality.Currently,the clinical management of CID is limited.The utilization of antidiarrheal medications,such as loperamide and octreotide,is relatively limited because of their unsatisfactory efficacy and adverse effects.In recent years,traditional Chinese medicine(TCM)has attracted great interest because of its beneficial effect in treating CID,which has multitarget and low-toxicity therapeutic characteristics.TCM exhibits remarkable therapeutic potential in the prevention and treatment of CID.It can alleviate and treat CID by regulating chemical drug metabolism,improving the integrity of the intestinal barrier,stimulating proliferation while suppressing the apoptosis of intestinal epithelial cells,ameliorating oxidative stress and inflammation and regulating bile acids and aquaporins.However,large-scale,randomized,double-blind clinical trials of TCM for the treatment of CID are lacking,and most preclinical experiments have not been translated to clinical trials.Accordingly,this review highlights the clinical efficacy and molecular mechanisms of TCM against CID via PubMed,Web of Science and China National Knowledge Infrastructure and proposes that future research on TCM against CID should focus on strengthening the connection from bench to bed,which may help to comprehensively evaluate the therapeutic potential of TCM against CID.
基金This work was financially supported by National Science and Technology Major Projects(No.2018ZX09201-011,2018ZX09301-011-003)the National High Technology Research and Development Program of China(No.2019YFC1711400)。
文摘Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.
基金supported by the National Natural Science Foundation of China(No.82322075).
文摘When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifungal drugs available for clinical use are limited,and their toxicity and safety issues can lead to adverse effects for patients.The emergence of drug-resistant strains and the“super fungus”Candida auris has further complicated treatment.Consequently,the identification of new antifungal medications and the formulation of effective combination therapy strategies have emerged as pivotal research priorities within this discipline.Natural products are specialized small molecules that are produced in nature and play pivotal roles in numerous cellular processes and are considered to be among the most significant pharmaceutical agents in the field of human healthcare.Accordingly,the objective of this paper is to review natural products and relevant compounds that exhibit antifungal activity by targeting key components of the fungal cell walls or cell membranes.We focused on the most recent research findings from 2022 to 2025 concerning antifungal natural products derived from plants,fungi,and bacteria,and conducted a comprehensive summary of the sources and types of natural products,along with their antifungal mechanisms of action.Furthermore,we analyzed the application prospects of combining novel natural products with existing antifungal drugs from the perspective of compensatory mechanisms of fungal cell structures,thus establishing new treatment strategies for fungal infections.
基金National Natural ScienceFoundation of China (grant number: 81973696).
文摘Gualou-Xiebai-Banxia Decoction(GXBD)is a traditional Chinese herbal formula including four traditional Chinese medicines:Gualou(Trichosanthis Fructus,TF),Xiebai(Allii Macrostemonis Bulbus,AMB),Banxia(Pinelliae Rhizoma,PR)and yellow wine.It is a classical therapy for chest stuffiness and pain syndrome and is widely used in the clinical treatment of coronary heart disease.It also shows significant therapeutic effects on pulmonary heart disease,hyperlipidemia,and arrhythmia.This study conducted a literature review and collected information on GXBD from databases such as PubMed,Web of Science,China National Knowledge Infrastructure,and ScienceDirect.The result indicated that the main active ingredients of GXBD are steroids,flavonoids,terpenoids,alkaloids,amino acids,and organic acids.Trigonelline,macrostemonoside and cucurbitacin B can provide reference for its quality control.GXBD may exert therapeutic effects on coronary heart disease through AMPK,PI3K-AKT,oxLDL,VEGF,and NF-κB signal pathways.This review provides a comprehensive analysis and summary of the chemical composition and in vivo metabolism of three traditional Chinese medicines(TF,AMB,and PR),along with an evaluation of the chemical composition,quality control,pharmacological effects,and clinical application of GXBD.Based on these,areas requiring further research on GXBD have been proposed to provide a reference for its further development and new drug research.
基金supported by the Special Funds for the Central Government to Guide Local Science and Technology Development(No.246Z7704G,China)National Natural Science Foundation of China(No.H2024110033,China).
文摘Pulmonary hypertension(PH)is a pulmonary vascular disease caused by multiple etiologies,characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure,which can lead to severe cardiovascular complications.The third type of PH,hypoxic pulmonary hypertension(HPH)caused by chronic lung disease and/or hypoxia,has complex and incomplete pathological mechanism.Current clinical treatment for HPH primarily focus on alleviating symptoms,with limited effectiveness in improving pulmonary vascular remodeling(PVR).Recent studies by various scholars have indicated that certain traditional Chinese medicine(TCM)monomers,extracts,and formulations can inhibit multiple signaling pathways,thereby suppressing pulmonary vascular remodeling and demonstrating favorable efficacy against HPH.This article reviews the pathogenesis of HPH,including pulmonary arterial wall thickening,immune inflammation,and thrombogenesis,and discusses the latest research advancements regarding the pharmacodynamic mechanisms of TCM in treating HPH.
基金supporting by the National Nature Science Foundation of China(Grant No.:82071215)the Outstanding Scientific Fund of Shengjing Hospital,China(Grant No.:202208).
文摘Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)reuptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antidepressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protection,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor receptor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.
基金the National Key Research and Development Program of China(2019YFC1710105).
文摘Background:Alzheimer’s disease(AD)is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment.Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs.Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects,which may be beneficial for the treatment of AD.However,the combination of active ingredients and their mechanisms remain unclear.Therefore,we aimed to identify potential active ingredients in F.assafoetida and their mechanisms of action against AD by using network pharmacology.Methods:In our study,an integrated network pharmacological approach,that included adsorption,distribution,metabolism and excretion screening,target identification,network construction,topological analysis,gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,and molecular docking,was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD.Results:The results indicated that 12 key active ingredients,obtained by topological analysis(including farnesiferol a,conferol,farnesiferol b,ferulic acid,etc.),may be the primary pharmacological components that may ameliorate AD.The 2 key significant pathways identified are the cholinergic synapse signaling pathway(critical targets include ACHE,CHRM1,CHRM2,MAPK1,PIK3CA,PIK3CB,PIK3CD,and PIK3CG)and the AD signaling pathway(critical targets include APP,BACE1,GSK3B,MAPK1,NCSTN,NOS1,PSEN1).These critical targets are closely related to the regulation of three typical pathological features of AD[central nervous system(CNS)cholinergic hypofunction,amyloid-β(Aβ)plaques,and hyperphosphorylated tau proteins].Finally,14 critical targets in the 2 key significant pathways were validated by molecular docking analysis.Conclusion:F.assafoetida may be effective for alleviating AD symptoms,through multi-component,multi-target,and multi-pathway synergistic effects,associated with the multiple pathogenesis hypotheses of AD.Our study may provide certain clues for the further development and utilization of this natural herbal medicine.
文摘Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.
基金Qihuang scholars of the talent project of inheriting and innovating"hundreds of millions"of traditional Chinese medicine(Qihuang project)。
文摘Objective:To investigate the possible molecular mechanism of panax notoginseng in the treatment of vitreous hemorrhage(VH).Methods:The active components of Panax notoginseng were screened by TCMSP database and the corresponding targets were collected.Vh-related gene targets were derived from GeneCards and OMIM database,and the target of Panax notoginseng was mapped to disease target genes.STRING database and Cytoscape 3.7.2 software were used to construct the protein-protein interaction(PPI)network diagram and the interaction network of"Pantoginseng-active ingredient-VH-target protein",and the core action target genes were screened out.Finally,gene body(GO)biological process and metabolic pathway enrichment analysis of KEGG were performed on the potential therapeutic targets.Results:We identified 8 active components,162 active component targets,1387 VHrelated genes and 75 candidate targets for VH.In the"Panax notoginseng-active ingredient-VH-target protein"interaction network,there are 82 nodes in total.The core target genes include AKT1,CASP3,VEGF-A,IL-6 and MMP-9.143 major enrichment pathways were identified by GO and KEGG enrichment analysis.The key signal pathways include age-RAGE signaling pathway,fluid shear stress and atherosclerosis,etc.,and the significant molecular functions include cytokine activity,receptor ligand activity,cytokine receptor binding,etc.Conclusion:The potential molecular mechanism of panax notoquinone in the treatment of VH is closely related to the biological processes of anti-angiogenesis,anti-inflammation,regulation of apoptosis and oxidative stress,and AKT1,CASP3,VEGF-A,IL-6 and MMP-9 may be the core target genes.
基金financially supported by the Shaanxi Province Key Project for Social Development(No.2022SF-205).
文摘Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.
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
基金Science and Technology Planning Project of Guangdong Province of China(2016A030303013)Science and Technology Planning Project of Guangdong Province of China(2017A020213001).
文摘Background:This study aimed to identify the main active components,targets and pathways of Yueju pill,explore its mechanism in the treatment of depressive polycystic ovary syndrome,so as to provide proofs for expanding the clinical application of Yueju pill.Methods:The active components and targets of Yueju pill were retrieved from the traditional Chinese medicine system pharmacology(TCMSP)database and analysis platform.GeneCards and OMIM were used to search the disease targets of polycystic ovary syndrome and depression.The intersection genes of drug and disease were obtained via venny.R.STRING 11.0 was adopted to construct PPI network,then we obtained the hub genes with count.R.Utilized Cytoscape 3.7.2 to construct the"drug-disease-active ingredientsproteins"network.Finally,the Bioconductor tools of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were applied to the enrichment of biological functions and pathways.Results:There were 37 compounds in the prescription of Yueju pill,and 83 intersection genes of Yueju pill and PCOS-Depression.The significant genes were IL6,VEGFA,EGF,MAPK1,ESR1,MAPK8,EGFR and MAPK14.Through the enrichment of GO and KEGG,we found 106 biological processes and 129 signaling pathways were related to the treatment of depressive polycystic ovary syndrome with Yueju pill.Conclusions:Our study could provide sufficient data in supporting Yueju pill to treat polycystic ovary syndrome,while the purpose of anti-depression should be achieved by relieving the systemic symptoms.This study would provide fresh insights for expanding the clinical application of Yueju pill.
基金supported by the National Key Research and Development Programme of China(No.2022YFF1100601)the National Natural Science Foundation of China(Nos.82321005,82373886,82173886 and 82404997)+3 种基金the Overseas Expertise Introduction Project for Discipline Innovation(No.G20582017001)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZ202402)the CAMS Innovation Fund for Medical Sciences(No.2021-12M-5-011)the China Postdoctoral Science Foundation(No.2022M723514).
文摘The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atherosclerosis.Recent studies have elucidated the interaction between natural medicines and this co-metabolism system.Upon oral administration,natural medicine ingredients can undergo transformation by gut microbiota,potentially enhancing their bioavailability or anti-atherogenic efficacy.Furthermore,natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism.This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites.It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines’intervention on key nodes of endogenous host-microbe co-metabolism.These insights may offer new perspectives for cardiovascular disease(CVD)treatment and guide future drug discovery efforts.
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
基金Supported by Major Project of Zhongshan Science and Technology Bureau(2021B3009).
文摘This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U21A20411 and 82074400)the Hunan ProvincialNatural Science Foundation,China(GrantNo.:2024JJ5303)+1 种基金the Scientific Research Project of Hunan University of Chinese Medicine,China(GrantNo.:Z2023XJYB05)the Postgraduate Scientific Research Innovation Project of Hunan,China(Grant No.:CX20220795).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune condition that leads to chronic arthritis,disability,and reduced lifespan.Current therapies show limited effectiveness and often cause severe side effects,with up to 50%of patients discontinuing disease-modifying antirheumatic drugs(DMARDs)due to unsatisfactory outcomes.Natural bioactive compounds(NBCs),such as glycosides,alkaloids,terpenoids,flavonoids,polyphenols,and coumarins,have gained attention for their immunomodulatory and antiinflammatory properties.However,challenges like poor solubility,high dosage requirements,short action duration,and low tissue specificity hinder their clinical use.Nanoparticle(NP)-based delivery systems,including lipid NPs(LNPs),polymer carriers,and inorganic nanocarriers,have been designed to address these challenges through passive,active,and stimuli-responsive strategies.NBC-loaded NPs target immune dysfunction,synovial hyperplasia,bone destruction,angiogenesis,inflammation,and oxidative stress(OS)in RA.This article highlights recent advancements in NBCs for RA treatment,nanoformulation design,and targeted mechanisms,while addressing challenges and future directions in this field.The integration of cutting-edge nanotechnology has demonstrated significant potential to overcome traditional barriers such as low bioavailability and off-target effects through intelligent NPs design.Future research should enhance artificial intelligence(AI)-driven modeling to predict drugnanocarrier interactions,develop biomarker frameworks for precision nanomedicine,and optimize RA management.
基金Supported by the National Natural Science Foundation of China,No.81904064Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A03804 and No.CI2021A05052Fundamental Research Funds for the Central Public Welfare Research Institutes,No.ZZ14-YQ-023,No.ZXKT21017,and No.ZXKT21024.
文摘Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.