Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and ...Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.展开更多
血液系统兼具“运输”与“制作”功能,负责氧气与二氧化碳、营养物质与代谢废物的循环运输。该系统一旦发生异常,可引发贫血、粒细胞缺乏、急性白血病或血栓性疾病。胞质分裂专用蛋白(Dedicator of cytokinesis,DOCK)家族蛋白通过调控Rh...血液系统兼具“运输”与“制作”功能,负责氧气与二氧化碳、营养物质与代谢废物的循环运输。该系统一旦发生异常,可引发贫血、粒细胞缺乏、急性白血病或血栓性疾病。胞质分裂专用蛋白(Dedicator of cytokinesis,DOCK)家族蛋白通过调控Rho GTPase、BCR、CXCR4、VEGF等信号通路,精准激活Rac/Cdc42,进而调节造血细胞趋化、黏附及免疫突触形成,在维系免疫细胞增殖、分化与机体稳态中发挥关键作用。DOCK家族蛋白功能缺陷可导致联合免疫缺陷、红细胞形态异常及反复感染等多种血液系统疾病。深入解析DOCK家族在血细胞中的作用机制,不仅为理解血液系统疾病发病理论提供新视角,也为临床防治策略的开发带来新方向。展开更多
The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used ...The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.展开更多
Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that ...Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.展开更多
Bio-inspired magnetic helical microrobots have great potential for biomedical and micromanipulation applications. Precise interaction with objects in liquid environments is an important prerequisite and challenge for ...Bio-inspired magnetic helical microrobots have great potential for biomedical and micromanipulation applications. Precise interaction with objects in liquid environments is an important prerequisite and challenge for helical microrobots to perform various tasks. In this study, an automatic control method is proposed to realize the axial docking of helical microrobots with arbitrarily placed cylindrical objects in liquid environments. The docking process is divided into ascent, approach, alignment, and insertion stages. First, a 3D docking path is planned according to the positions and orientations of the microrobot and the target object. Second, a steering-based 3D path-following controller guides the helical microrobot to rise away from the container bottom and approach the target along the path. Third, based on path design with gravity compensation and steering output limits, alignment of position and orientation can be accomplished simultaneously. Finally, the helical microrobot completes the docking under the rotating magnetic field along the target orientation. Experiments verified the automatic docking of the helical microrobot with static targets, including connecting with micro-shafts and inserting into micro-tubes. The object grasping of a reconfigurable helical microrobot aided by 3D automatic docking was also demonstrated. This method enables precise docking of helical microrobots with objects, which might be used for capture and sampling, in vivo navigation control, and functional assembly of microrobots.展开更多
Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive ski...Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive skin were likely to be more susceptible to hyperpigmentation.However,the association between sensitive skin and hyperpigmentation,as well as the underlying molecular mechanisms,remain unclear.Objective:This study aims to investigate the correlation and intrinsic mechanisms between sensitive skin and hyperpigmentation through network pharmacology combined with molecular docking.Materials and Methods:The targets associated with sensitive skin and hyperpigmentation were collected from the human gene database,GeneCards.Subsequently,the protein-protein interaction(PPI)network,Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Ontology(GO)enrichment analysis were performed to explore the biological connections between sensitive skin and hyperpigmentation.Additionally,the targets of 15 active compounds with reported lightening effects were collected from TCMSP,BATMAN and SymMap databases.Target analysis and molecular docking were performed to identify potential candidates for addressing hyperpigmentation on sensitive skin.The anti-melanogenesis effect of the identified candidate was verified in B16F10 cells.Results:A total of 16971 sensitive skin targets and 11382 hyperpigmentation targets were screened,and 9693 overlapping targets were identified,with a core set comprising 164 targets.The combination of PPI network,KEGG and GO analysis revealed the key role of tyrosinase and immune-mediated inflammation in pigmentation on sensitive skin.Among the 15 active compounds,oxyresveratrol was identified as having a high correlation with the core set targets and predicted strong inhibition of Tyrosine-protein Kinase Kit.The application of oxyresveratrol exhibited a dose-dependent suppression of melanin production in B16F10 cells.Conclusion:This study suggested the crucial roles of immune-mediated inflammation in sensitive skin and hyperpigmentation,as well as highlighted the potential of oxyresveratrol in addressing hyperpigmentation on sensitive skin.These comprehensive findings provide a deeper understanding of the connection mechanism between sensitive skin and hyperpigmentation,offering new insights for the development of targeted treatments and interventions.展开更多
To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmac...To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.展开更多
The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on...The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L.(hemp)seeds,particularly hemp seed proteins.Therefore,this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins.To confirm the complete hydrolysis of hemp seed proteins during the fermentation process,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was employed.Further,the isolation and purification of peptides were achieved through ultrafiltration.The identity of peptides was nextly established using ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS).The results revealed a total of 39 identified peptides in fermented hemp seeds,with 9 peptides selected based on their relative quantity.Notably,AAELIGVP(P1),AAVPYPQ(P2),VFPEVAP(P4),DVIGVPLG(P6),and PVPKVL(P9)demonstrated strong anti-inflammatory abilities in lipopolysaccharide(LPS)-induced RAW264.7 macrophage cells.Molecular docking was used to understand the potential anti-inflammatory mechanism of these 5 peptides,and in silico results indicated that P1,P2,P4,P6,and P9 could bind to the active sites of toll-like receptor 4(TLR-4),nuclear factor-κB(NF-κB),and inhibitor of NF-κB kinase(IKK)with higher binding energies.Overall,these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.展开更多
Objective:To predict the nephrotoxicity mechanism of Lianqiao-4 through network pharmacology and molecular docking methods.Methods:The main chemical components of Lianqiao(Forsythia suspensa),Bistortae rhizoma,Ophiopo...Objective:To predict the nephrotoxicity mechanism of Lianqiao-4 through network pharmacology and molecular docking methods.Methods:The main chemical components of Lianqiao(Forsythia suspensa),Bistortae rhizoma,Ophiopogonis radix,and Clematidis radix et rhizoma,as well as nephrotoxicity-related targets,were screened through databases such as TCMSP,Swiss Target Prediction,GeneCards,and ETCM.Venny 2.1.0 was used to identify the main components of Lianqiao-4 and nephrotoxicity targets.The STRING platform and David database were utilized to construct a protein-protein interaction(PPI)network diagram,while gene function(GO)enrichment analysis and KEGG pathway analysis were conducted.The“Lianqiao-4 active ingredients-nephrotoxicity targets-signaling pathways”network model was constructed using Cytoscape 3.9.1 software.Results:Network pharmacology and molecular docking analysis revealed that the core active ingredients responsible for the nephrotoxicity mechanism of Mongolian medicine Lianqiao-4 include steroidal saponins such as ophiopogonin A,flavonoids like kaempferol and quercetin,steroidal compounds such asβ-sitosterol and sitosterol,and other key regulatory targets including STAT3,ABCG2,HSP90AA1,MMP9,PTGS2,and EGFR.Major pathways involved include lipid and atherosclerosis,chemical carcinogenesis-DNA adducts,and arachidonic acid metabolism.Conclusion:Mongolian medicine Lianqiao-4 exerts its therapeutic effect on nephrotoxicity through multiple components,targets,and pathways,pending experimental verification.展开更多
Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims ...Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims to examine the volatile compounds and antibacterial effect of P.anisum essential oil(PAEO)as well as for the first time its genotoxicity employing both in vitro and computational approaches.Gas chromatography-mass spectrometry(GC-MS)analysis identified anethole as the principal compound,which comprises 92.47%of PAEO.PAEO was tested for its potential antibacterial properties against Bacillus subtilis ATCC 6633,Listeria innocua ATCC 33090,Staphylococcus aureus ATCC 29213,Klebsiella aerogenes ATCC 13048,and a clinical strain of Salmonella enterica serotype Typhi.PAEO displayed noteworthy antibacterial action toward all tested bacteria,especially Staphylococcus aureus,with an inhibition zone of 21.43±0.87 mm,as determined by the disc-diffusion test.Varied between 0.0625%and 2%v/v,while the MBC values ranged from 0.125%to 8%v/v,reflecting the strength of the tested EO.The MBC/MIC ratios indicated the bactericidal nature of PAEO.The results of molecular docking revealed strong binding interactions between key PAEO molecules and microbial target proteins.ADMET(Absorption,Distribution,Metabolism,Excretion,and Toxicity)analysis confirmed favorable pharmacokinetic properties,indicating its potential as a safe therapeutic agent.Additionally,genotoxicity was assessed using the comet assay,which demonstrated minimal genotoxic risk,affirming the oil’s safety.These results highlight the promising antimicrobial properties of PAEO and its possible use as an active agent in the pharmacy,food,and cosmetic sectors.展开更多
Background:Pistacia integerrima,a cornerstone of traditional medicine,is renowned for its therapeutic applications against various health conditions,including cancer and hepatitis.This study investigates the pharmacol...Background:Pistacia integerrima,a cornerstone of traditional medicine,is renowned for its therapeutic applications against various health conditions,including cancer and hepatitis.This study investigates the pharmacological potential of bioactive compounds derived from Pistacia integerrima in inhibiting 5-lipoxygenase(5-LOX),a key enzyme implicated in inflammation and cancer progression.The current study aimed to evaluate the lipoxygenase inhibitory activity of bioactive compounds from Pistacia integerrima and assess their potential for therapeutic development in the context of inflammation and cancer treatment.Methods:Three major compounds-spinacetin(1),patuletin(2),and pistagremic acid(3)-were isolated from Pistacia integerrima and analyzed for their lipoxygenase inhibitory activity.Biochemical assays and molecular docking studies were performed to assess their effectiveness in inhibiting 5-LOX.Results:All three compounds demonstrated significant inhibition of lipoxygenase activity.Spinacetin(1)and patuletin(2)exhibited the most potent inhibitory effects,with IC_(50)values of 40.34μM and 45.04μM,respectively.Molecular docking studies revealed that patuletin(2)had the highest binding affinity(−7.717 kcal/mol)against 5-LOX,followed by spinacetin(1)with a binding affinity of−6.074 kcal/mol.In-depth in silico analysis highlighted the drug-likeness of spinacetin(1)and its favorable toxicological profile,suggesting its suitability for therapeutic development.Conclusion:The study demonstrates that compounds from Pistacia integerrima,particularly spinacetin and patuletin,have significant lipoxygenase inhibitory activity,with spinacetin showing promise as a lead candidate for lipoxygenase-targeted therapies.The findings reinforce the therapeutic relevance of Pistacia integerrima and suggest that its bioactive compounds may serve as safer,plant-based alternatives to conventional anti-inflammatory and anticancer treatments.展开更多
BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea t...BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea to drink with light yellow and special aroma for health care.It has high potential economic medicinal value.Colon adenocarcinoma(COAD)is the third most frequent malignancy and its incidence and mortality is increasing.However,the current common treatments for COAD bring great side effects.In recent years,natural products and their various de-rivatives have shown significant potential to supplement conventional therapies and to reduce associated toxicity while improving efficacy.In order to overcome the limitations of traditional treatment methods,the global demand and development of natural anti-COAD drugs were increasingly hindered.AIM To investigate the potential targets and mechanisms of Camellia luteoflora anti-COAD.METHODS Nuclear magnetic resonance and mass spectrometry was used to identified the compounds of Camellia luteoflora.Network pharmacology analysis and survival analysis was used in this study to investigate the anti-COAD effect and mechanism of Camellia luteoflora.RESULTS Firstly,a total of 13 compounds were identified.Secondly,10 active ingredients for 204 potential targets were screened and protein-protein interaction analysis showed that TP53,STAT3,ESR1,MAPK8,AKR1C3,RELA,CYP19A1,CYP1A1,JUN and CYP17A1 were hub targets.GO and KEGG enrichment analyses revealed that Camellia luteoflora exerted anti-COAD effect through multiple functions and pathways.Then,the analysis of survival and stage indicated that TP53 was highly expressed in COAD and the overall survival of high-TP53 and high-CYP19A1 COAD patients was significantly shorter than the low group and there was significant difference in MAPK and RELA expression between different stages.Finally,the molecular docking results demonstrated the binding affinities and sites between active ingredients and TP53,STAT3,ESR1.CONCLUSION Our study systematically demonstrated the potential anti-COAD mechanism of Camellia luteoflora and provided a theoretical basis for its further application in the COAD treatment.展开更多
Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditio...Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.展开更多
The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacol...The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacology and molecular docking methods were used to investigate the mechanism of action of SNL against ulcerative colitis(UC).A total of 282 component target genes and 1850 disease target genes were obtained,and 157 cross-targets and 16 core-targets were obtained after crossover.A total of 20 signaling pathways such as anti-inflammatory and anti-apoptotic were obtained by GO analysis and KEGG analysis,respectively.It is possible that the anti UC eff ect can be achieved by regulating proteins such as AKT1,EGFR,NFKB1,JUN,and HSP90AA1.Molecular docking results show that the anti UC active ingredients are well docked with the target protein molecules This study provides a scientific basis for the development and utilization of SNL.展开更多
[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained...[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained through literature research(January 1942 to January 2021).Active components and potential targets of limonoids were retrieved from PubChem,TCMSP,and Swiss Target Prediction databases.AD-related targets were obtained from the GeneCards database,and intersecting targets were identified using Venny 2.1.0 to obtain the action targets of limonoids against AD.The protein-protein interaction(PPI)network was constructed using the String platform,and key targets were screened and visualized via network topology analysis with Cytoscape software.GO and KEGG pathway enrichment analyses were performed using the Metascape database,and a"drug-component-target-pathway-disease"network diagram was constructed using Cytoscape.AutoDock was empolyed for molecular docking to predict the binding properties of limonoid active components and their targets.[Results]A total of 60 limonoid compounds were obtained from literature research.Network pharmacology analysis showed 58 effective active components and 134 common targets between limonoids and AD.Key targets included AKT1(serine/threonine-protein kinase 1),TNF(tumor necrosis factor),STAT3(signal transducer and activator of transcription 3),BCL2(B-cell lymphoma 2),and EGFR(epidermal growth factor receptor).KEGG enrichment analysis revealed key signaling pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycans in cancer,MAPK signaling pathway,and Ras signaling pathway.Molecular docking results indicated that aphanamixoid A,obacunol,cipadesin C,harpertrioate A,xylogranatin A,11-oxocneorin G,evodulone,methyl angolensate,harrpemoid B and khivorin may be key components of limonoids against AD.[Conclusions]Limonoids exert anti-Alzheimer s effects through a multi-molecule,multi-target and multi-pathway mechanism.展开更多
Objective:To analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology,molecular docking technology,and experimental studies.Method:Using network pharmacology,the chemical ...Objective:To analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology,molecular docking technology,and experimental studies.Method:Using network pharmacology,the chemical components and core target proteins of the Jiawei Sanpian decoction were analyzed.Key chemical components were docked with core targets using mo-lecular docking,and the results were visualized.Nitroglycerin was injected into the dorsal cervical region to establish a rat migraine model.Finally,experiments were conducted to verify the effects of Jiawei Sanpian on related pathways and targets.Results:Four notable chemical components were identified,namely,b-sitosterol,quercetin,mairin,and kaempferol.Five representative targets were identified,namely,insulin-like growth factor 1(IGF-1),matrix metallopeptidase 2(MMP-2),interleukin-2(IL-2),superoxide dismutase 2(SOD2),and inducible nitric oxide synthase(NOS2).Molecular docking results revealed that the minimum binding energies between the four chemical components and the five targets were below5 kcal/mol,indicating favor-able binding activity.Enzyme linked immunosorbent assay(ELISA)results demonstrated the efficacy of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1,IL-2,MMP-2,and SOD2(P<0.001).Real-time quantitative polymerase chain reaction(RT-qPCR)results demonstrated the effectiveness of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1,IL-2,MMP-2,and SOD2(P<0.001).After using erastin,the therapeutic effect of Jiawei Sanpian decoction declined.Conclusion:This study provides initial insights into the complex and multilayered therapeutic mecha-nisms of Jiawei Sanpian decoction in treating migraine,primarily through its diverse components,tar-gets,and pathways.These findings indicate that Jiawei Sanpian decoction may exert its effects mainly through processes linked to the mitochondrial inflammatory pathway,thereby providing therapeutic benefits for migraine.展开更多
文摘Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.
文摘血液系统兼具“运输”与“制作”功能,负责氧气与二氧化碳、营养物质与代谢废物的循环运输。该系统一旦发生异常,可引发贫血、粒细胞缺乏、急性白血病或血栓性疾病。胞质分裂专用蛋白(Dedicator of cytokinesis,DOCK)家族蛋白通过调控Rho GTPase、BCR、CXCR4、VEGF等信号通路,精准激活Rac/Cdc42,进而调节造血细胞趋化、黏附及免疫突触形成,在维系免疫细胞增殖、分化与机体稳态中发挥关键作用。DOCK家族蛋白功能缺陷可导致联合免疫缺陷、红细胞形态异常及反复感染等多种血液系统疾病。深入解析DOCK家族在血细胞中的作用机制,不仅为理解血液系统疾病发病理论提供新视角,也为临床防治策略的开发带来新方向。
基金supported by 2024 Liaoning Province Graduate Education Teaching Reform Research Project(LNYJG2024251).
文摘The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.
文摘Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.
基金supported by the National Natural Science Foundation of China(No.62273117)Pre-research Task(No.SKLRS202418B)of State Key Laboratory of Robotics and Systems(HIT).
文摘Bio-inspired magnetic helical microrobots have great potential for biomedical and micromanipulation applications. Precise interaction with objects in liquid environments is an important prerequisite and challenge for helical microrobots to perform various tasks. In this study, an automatic control method is proposed to realize the axial docking of helical microrobots with arbitrarily placed cylindrical objects in liquid environments. The docking process is divided into ascent, approach, alignment, and insertion stages. First, a 3D docking path is planned according to the positions and orientations of the microrobot and the target object. Second, a steering-based 3D path-following controller guides the helical microrobot to rise away from the container bottom and approach the target along the path. Third, based on path design with gravity compensation and steering output limits, alignment of position and orientation can be accomplished simultaneously. Finally, the helical microrobot completes the docking under the rotating magnetic field along the target orientation. Experiments verified the automatic docking of the helical microrobot with static targets, including connecting with micro-shafts and inserting into micro-tubes. The object grasping of a reconfigurable helical microrobot aided by 3D automatic docking was also demonstrated. This method enables precise docking of helical microrobots with objects, which might be used for capture and sampling, in vivo navigation control, and functional assembly of microrobots.
文摘Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive skin were likely to be more susceptible to hyperpigmentation.However,the association between sensitive skin and hyperpigmentation,as well as the underlying molecular mechanisms,remain unclear.Objective:This study aims to investigate the correlation and intrinsic mechanisms between sensitive skin and hyperpigmentation through network pharmacology combined with molecular docking.Materials and Methods:The targets associated with sensitive skin and hyperpigmentation were collected from the human gene database,GeneCards.Subsequently,the protein-protein interaction(PPI)network,Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Ontology(GO)enrichment analysis were performed to explore the biological connections between sensitive skin and hyperpigmentation.Additionally,the targets of 15 active compounds with reported lightening effects were collected from TCMSP,BATMAN and SymMap databases.Target analysis and molecular docking were performed to identify potential candidates for addressing hyperpigmentation on sensitive skin.The anti-melanogenesis effect of the identified candidate was verified in B16F10 cells.Results:A total of 16971 sensitive skin targets and 11382 hyperpigmentation targets were screened,and 9693 overlapping targets were identified,with a core set comprising 164 targets.The combination of PPI network,KEGG and GO analysis revealed the key role of tyrosinase and immune-mediated inflammation in pigmentation on sensitive skin.Among the 15 active compounds,oxyresveratrol was identified as having a high correlation with the core set targets and predicted strong inhibition of Tyrosine-protein Kinase Kit.The application of oxyresveratrol exhibited a dose-dependent suppression of melanin production in B16F10 cells.Conclusion:This study suggested the crucial roles of immune-mediated inflammation in sensitive skin and hyperpigmentation,as well as highlighted the potential of oxyresveratrol in addressing hyperpigmentation on sensitive skin.These comprehensive findings provide a deeper understanding of the connection mechanism between sensitive skin and hyperpigmentation,offering new insights for the development of targeted treatments and interventions.
文摘To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.
基金the 4^(th) Brain Korea(BK)21 Plus Project(4299990913942)financed by the Korean Government,Republic of Korea.
文摘The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L.(hemp)seeds,particularly hemp seed proteins.Therefore,this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins.To confirm the complete hydrolysis of hemp seed proteins during the fermentation process,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was employed.Further,the isolation and purification of peptides were achieved through ultrafiltration.The identity of peptides was nextly established using ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS).The results revealed a total of 39 identified peptides in fermented hemp seeds,with 9 peptides selected based on their relative quantity.Notably,AAELIGVP(P1),AAVPYPQ(P2),VFPEVAP(P4),DVIGVPLG(P6),and PVPKVL(P9)demonstrated strong anti-inflammatory abilities in lipopolysaccharide(LPS)-induced RAW264.7 macrophage cells.Molecular docking was used to understand the potential anti-inflammatory mechanism of these 5 peptides,and in silico results indicated that P1,P2,P4,P6,and P9 could bind to the active sites of toll-like receptor 4(TLR-4),nuclear factor-κB(NF-κB),and inhibitor of NF-κB kinase(IKK)with higher binding energies.Overall,these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.
文摘Objective:To predict the nephrotoxicity mechanism of Lianqiao-4 through network pharmacology and molecular docking methods.Methods:The main chemical components of Lianqiao(Forsythia suspensa),Bistortae rhizoma,Ophiopogonis radix,and Clematidis radix et rhizoma,as well as nephrotoxicity-related targets,were screened through databases such as TCMSP,Swiss Target Prediction,GeneCards,and ETCM.Venny 2.1.0 was used to identify the main components of Lianqiao-4 and nephrotoxicity targets.The STRING platform and David database were utilized to construct a protein-protein interaction(PPI)network diagram,while gene function(GO)enrichment analysis and KEGG pathway analysis were conducted.The“Lianqiao-4 active ingredients-nephrotoxicity targets-signaling pathways”network model was constructed using Cytoscape 3.9.1 software.Results:Network pharmacology and molecular docking analysis revealed that the core active ingredients responsible for the nephrotoxicity mechanism of Mongolian medicine Lianqiao-4 include steroidal saponins such as ophiopogonin A,flavonoids like kaempferol and quercetin,steroidal compounds such asβ-sitosterol and sitosterol,and other key regulatory targets including STAT3,ABCG2,HSP90AA1,MMP9,PTGS2,and EGFR.Major pathways involved include lipid and atherosclerosis,chemical carcinogenesis-DNA adducts,and arachidonic acid metabolism.Conclusion:Mongolian medicine Lianqiao-4 exerts its therapeutic effect on nephrotoxicity through multiple components,targets,and pathways,pending experimental verification.
文摘Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims to examine the volatile compounds and antibacterial effect of P.anisum essential oil(PAEO)as well as for the first time its genotoxicity employing both in vitro and computational approaches.Gas chromatography-mass spectrometry(GC-MS)analysis identified anethole as the principal compound,which comprises 92.47%of PAEO.PAEO was tested for its potential antibacterial properties against Bacillus subtilis ATCC 6633,Listeria innocua ATCC 33090,Staphylococcus aureus ATCC 29213,Klebsiella aerogenes ATCC 13048,and a clinical strain of Salmonella enterica serotype Typhi.PAEO displayed noteworthy antibacterial action toward all tested bacteria,especially Staphylococcus aureus,with an inhibition zone of 21.43±0.87 mm,as determined by the disc-diffusion test.Varied between 0.0625%and 2%v/v,while the MBC values ranged from 0.125%to 8%v/v,reflecting the strength of the tested EO.The MBC/MIC ratios indicated the bactericidal nature of PAEO.The results of molecular docking revealed strong binding interactions between key PAEO molecules and microbial target proteins.ADMET(Absorption,Distribution,Metabolism,Excretion,and Toxicity)analysis confirmed favorable pharmacokinetic properties,indicating its potential as a safe therapeutic agent.Additionally,genotoxicity was assessed using the comet assay,which demonstrated minimal genotoxic risk,affirming the oil’s safety.These results highlight the promising antimicrobial properties of PAEO and its possible use as an active agent in the pharmacy,food,and cosmetic sectors.
文摘Background:Pistacia integerrima,a cornerstone of traditional medicine,is renowned for its therapeutic applications against various health conditions,including cancer and hepatitis.This study investigates the pharmacological potential of bioactive compounds derived from Pistacia integerrima in inhibiting 5-lipoxygenase(5-LOX),a key enzyme implicated in inflammation and cancer progression.The current study aimed to evaluate the lipoxygenase inhibitory activity of bioactive compounds from Pistacia integerrima and assess their potential for therapeutic development in the context of inflammation and cancer treatment.Methods:Three major compounds-spinacetin(1),patuletin(2),and pistagremic acid(3)-were isolated from Pistacia integerrima and analyzed for their lipoxygenase inhibitory activity.Biochemical assays and molecular docking studies were performed to assess their effectiveness in inhibiting 5-LOX.Results:All three compounds demonstrated significant inhibition of lipoxygenase activity.Spinacetin(1)and patuletin(2)exhibited the most potent inhibitory effects,with IC_(50)values of 40.34μM and 45.04μM,respectively.Molecular docking studies revealed that patuletin(2)had the highest binding affinity(−7.717 kcal/mol)against 5-LOX,followed by spinacetin(1)with a binding affinity of−6.074 kcal/mol.In-depth in silico analysis highlighted the drug-likeness of spinacetin(1)and its favorable toxicological profile,suggesting its suitability for therapeutic development.Conclusion:The study demonstrates that compounds from Pistacia integerrima,particularly spinacetin and patuletin,have significant lipoxygenase inhibitory activity,with spinacetin showing promise as a lead candidate for lipoxygenase-targeted therapies.The findings reinforce the therapeutic relevance of Pistacia integerrima and suggest that its bioactive compounds may serve as safer,plant-based alternatives to conventional anti-inflammatory and anticancer treatments.
基金Supported by Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2023]-554and the National Natural Science Foundation of China,No.32360144.
文摘BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea to drink with light yellow and special aroma for health care.It has high potential economic medicinal value.Colon adenocarcinoma(COAD)is the third most frequent malignancy and its incidence and mortality is increasing.However,the current common treatments for COAD bring great side effects.In recent years,natural products and their various de-rivatives have shown significant potential to supplement conventional therapies and to reduce associated toxicity while improving efficacy.In order to overcome the limitations of traditional treatment methods,the global demand and development of natural anti-COAD drugs were increasingly hindered.AIM To investigate the potential targets and mechanisms of Camellia luteoflora anti-COAD.METHODS Nuclear magnetic resonance and mass spectrometry was used to identified the compounds of Camellia luteoflora.Network pharmacology analysis and survival analysis was used in this study to investigate the anti-COAD effect and mechanism of Camellia luteoflora.RESULTS Firstly,a total of 13 compounds were identified.Secondly,10 active ingredients for 204 potential targets were screened and protein-protein interaction analysis showed that TP53,STAT3,ESR1,MAPK8,AKR1C3,RELA,CYP19A1,CYP1A1,JUN and CYP17A1 were hub targets.GO and KEGG enrichment analyses revealed that Camellia luteoflora exerted anti-COAD effect through multiple functions and pathways.Then,the analysis of survival and stage indicated that TP53 was highly expressed in COAD and the overall survival of high-TP53 and high-CYP19A1 COAD patients was significantly shorter than the low group and there was significant difference in MAPK and RELA expression between different stages.Finally,the molecular docking results demonstrated the binding affinities and sites between active ingredients and TP53,STAT3,ESR1.CONCLUSION Our study systematically demonstrated the potential anti-COAD mechanism of Camellia luteoflora and provided a theoretical basis for its further application in the COAD treatment.
基金supported by the National Natural Science Foundation of China(82374367)Jiangxi Provincial Natural Science Foundation(20242BAB26163,20232BAB206144)+4 种基金Jiangxi Province Key Laboratory of Traditional Chinese Medicine for Cardiovascular Diseases(20242BCC32096)NATCM’s Project of High-level Construction of Key TCM Disciplines(zyyzdxk-2023113)Project of Key Discipline Construction Fund of Jiangxi University of Chinese Medicine(2023jzzdxk032)Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22011)National Traditional Chinese Medicine Inheritance and Innovation Center Construction Project.
文摘Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.
文摘The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacology and molecular docking methods were used to investigate the mechanism of action of SNL against ulcerative colitis(UC).A total of 282 component target genes and 1850 disease target genes were obtained,and 157 cross-targets and 16 core-targets were obtained after crossover.A total of 20 signaling pathways such as anti-inflammatory and anti-apoptotic were obtained by GO analysis and KEGG analysis,respectively.It is possible that the anti UC eff ect can be achieved by regulating proteins such as AKT1,EGFR,NFKB1,JUN,and HSP90AA1.Molecular docking results show that the anti UC active ingredients are well docked with the target protein molecules This study provides a scientific basis for the development and utilization of SNL.
基金Supported by Science and Technology Fund of Guizhou health and Health Committee(gzwkj2024-240)Anshun City Science and Technology Bureau(ASKS[2024]01).
文摘[Objectives]This study was conducted to explore the action mechanism of limonoids against Alzheimer s disease(AD)based on network pharmacology and molecular docking techniques.[Methods]Limonoid compounds were obtained through literature research(January 1942 to January 2021).Active components and potential targets of limonoids were retrieved from PubChem,TCMSP,and Swiss Target Prediction databases.AD-related targets were obtained from the GeneCards database,and intersecting targets were identified using Venny 2.1.0 to obtain the action targets of limonoids against AD.The protein-protein interaction(PPI)network was constructed using the String platform,and key targets were screened and visualized via network topology analysis with Cytoscape software.GO and KEGG pathway enrichment analyses were performed using the Metascape database,and a"drug-component-target-pathway-disease"network diagram was constructed using Cytoscape.AutoDock was empolyed for molecular docking to predict the binding properties of limonoid active components and their targets.[Results]A total of 60 limonoid compounds were obtained from literature research.Network pharmacology analysis showed 58 effective active components and 134 common targets between limonoids and AD.Key targets included AKT1(serine/threonine-protein kinase 1),TNF(tumor necrosis factor),STAT3(signal transducer and activator of transcription 3),BCL2(B-cell lymphoma 2),and EGFR(epidermal growth factor receptor).KEGG enrichment analysis revealed key signaling pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycans in cancer,MAPK signaling pathway,and Ras signaling pathway.Molecular docking results indicated that aphanamixoid A,obacunol,cipadesin C,harpertrioate A,xylogranatin A,11-oxocneorin G,evodulone,methyl angolensate,harrpemoid B and khivorin may be key components of limonoids against AD.[Conclusions]Limonoids exert anti-Alzheimer s effects through a multi-molecule,multi-target and multi-pathway mechanism.
基金funded by the National Natural Science Foundation of China(81873256)Natural Science Foundation of Xiamen(3502Z202371045).
文摘Objective:To analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology,molecular docking technology,and experimental studies.Method:Using network pharmacology,the chemical components and core target proteins of the Jiawei Sanpian decoction were analyzed.Key chemical components were docked with core targets using mo-lecular docking,and the results were visualized.Nitroglycerin was injected into the dorsal cervical region to establish a rat migraine model.Finally,experiments were conducted to verify the effects of Jiawei Sanpian on related pathways and targets.Results:Four notable chemical components were identified,namely,b-sitosterol,quercetin,mairin,and kaempferol.Five representative targets were identified,namely,insulin-like growth factor 1(IGF-1),matrix metallopeptidase 2(MMP-2),interleukin-2(IL-2),superoxide dismutase 2(SOD2),and inducible nitric oxide synthase(NOS2).Molecular docking results revealed that the minimum binding energies between the four chemical components and the five targets were below5 kcal/mol,indicating favor-able binding activity.Enzyme linked immunosorbent assay(ELISA)results demonstrated the efficacy of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1,IL-2,MMP-2,and SOD2(P<0.001).Real-time quantitative polymerase chain reaction(RT-qPCR)results demonstrated the effectiveness of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1,IL-2,MMP-2,and SOD2(P<0.001).After using erastin,the therapeutic effect of Jiawei Sanpian decoction declined.Conclusion:This study provides initial insights into the complex and multilayered therapeutic mecha-nisms of Jiawei Sanpian decoction in treating migraine,primarily through its diverse components,tar-gets,and pathways.These findings indicate that Jiawei Sanpian decoction may exert its effects mainly through processes linked to the mitochondrial inflammatory pathway,thereby providing therapeutic benefits for migraine.
