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Objective:
To investigate the regulation mechanism of baicalin on triple negative breast cancer (TNBC)'s biological network by a systematic biological strategy and cytology experiment.
Methods:
A systematic biological methodology is utilized to predict the potential targets of baicalin, collect the genes of TNBC, and analyze the TNBC and baicali...
Context in source publication
Context 1
... the potential target protection, totally 130 human's potential targets are collected. Among them, SWISS gets 71 human's potential targets; SEA gets 31 human's potential targets; Pubchem gets 30 human's potential targets; STITCH gets 10 human's potential targets. Metascape was utilized to exhibit distribution of potential targets (Fig. 6). In the outer circle, red, purple, green, blue represent potential targets come from Pubchem, SWISS, STITCH, SEA, respectively. In the inner circle, the greater the number of purple links and the longer the dark orange arc, the more overlap between the input target lists. The blue link indicates the amount of functional overlap ...
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Introduction: This paper is the product of the research "Biological network nanosensors for diabetes control with the issuance of alerts to users", developed in the technological faculty of the Francisco José de Caldas District University carried out during 2018 and 2019. Problem: Diabetes is a disease that affects most of the adult population and...
Citations
... Meanwhile, Notch, PI3K/AKT, and MAPK signaling mediate the effects of baicalin in restraining malignancies [503]. Additionally, researchers have used various approaches, based on systematic biological analyses of intersected targets of baicalin and diseases, to determine the molecular relationships underlying the effects of baicalin treatment [504]. c-MYC-driven onco-miRNAs and competitive endogenous RNAs have been captured in experiments to identify molecules that contribute to the pro-apoptotic effects of baicalin in cancer [505]. ...
Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC. Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.
... Liu et al. revealed that baicalin might have a potential therapeutic effect on breast cancer metastasis by regulating TGF-β1-dependent EMT progression [29]. Yang and co-workers revealed that baicalin could increase the expression of E-cadherin mRNA and decrease the expression of vimentin, β-catenin, c-Myc, and MMP-7 mRNA in LPS-induced MDA-MB-231 cells [30]. ...
Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE–RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine–AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol–AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.
... Some other reported anti-proliferative actions of baicalin include its effect against osteosarcoma, bladder, hepatoblastoma, mucoepidermoid, skin, colorectal, cervical, and triple negative breast cancer [265][266][267][268][269][270][271][272][273][274][275] . ...
Gout is an inflammatory disease caused by metabolic disorder or genetic inheritance. People throughout the world are strongly dependent on ethnomedicine for the treatment of gout and some receive satisfactory curative treatment. The natural remedies as well as established drugs derived from natural sources or synthetically made exert their action by mechanisms that are closely associated with anticancer treatment mechanisms regarding inhibition
of xanthine oxidase, feedback inhibition of de novo purine synthesis, depolymerization and disappearance of microtubule, inhibition of NF-ĸB activation, induction of TRAIL, promotion of apoptosis, and caspase activation and proteasome inhibition. Some anti-gout and anticancer novel compounds interact with same receptors for their action, e.g., colchicine and colchicine analogues. Dietary flavonoids, i.e., chrysin, kaempferol, quercetin, fisetin, pelargonidin,
apigenin, luteolin, myricetin, isorhamnetin, phloretinetc etc. have comparable IC50 values with established anti-gout drug and effective against both cancer and gout. Moreover, a noticeable number of newer anticancer compounds have already been isolated from plants that have been using by local traditional healers and herbal practitioners to treat gout. Therefore, the anti-gout plants might have greater potentiality to become selective candidates for screening
of newer anticancer leads
... Some other reported anti-proliferative actions of baicalin include its effect against osteosarcoma, bladder, hepatoblastoma, mucoepidermoid, skin, colorectal, cervical, and triple negative breast cancer [265][266][267][268][269][270][271][272][273][274][275] . ...
Gout is an inflammatory disease caused by metabolic disorder or genetic inheritance. People throughout the world are strongly dependent on ethnomedicine for the treatment of gout and some receive satisfactory curative treatment. The natural remedies as well as established drugs derived from natural sources or synthetically made exert their action by mechanisms that are closely associated with anticancer treatment mechanisms regarding inhibition of xanthine oxidase (XO), feedback inhibition of de novo purine synthesis, depolymerization and disappearance of microtubule, inhibition of NFĸB activation, induction of TRAIL, promotion of apoptosis, and caspase activation and proteasome inhibition. Some anti-gout and anticancer novel compounds interact with same receptors for their action e.g., colchicine and colchicine analogues. Dietary flavonoids i.e. chrysin, kaempferol, quercetin, fisetin, pelargonidin, apigenin, luteolin, myricetin, isorhamnetin, phloretinetc etc. have comparable IC50 values with established anti-gout drug and effective against both cancer and gout. Moreover, a noticeable number of newer anticancer compounds have already been isolated from plants that have been using by local traditional healers and herbal practitioners to treat gout. Therefore, the anti-gout plants might have greater potentiality to become selective candidate for screening of newer anticancer leads.
... erefore, this research hopes to propose a new method to analyze the regulatory mechanism of Radix Rhei Et Rhizome on CI biological networks. e development of high-throughput omics and chemoinformatics has given the opportunity to analyze the mechanisms of natural plant components for disease treatment [20][21][22][23][24]. erefore, based on previous research, this study will integrate proteomics and chemoinformatics strategies to further explore the molecular mechanism of Radix Rhei Et Rhizome's intervention in CI and provide reference information for new drug development and its clinical application. ...
Objective. To explore the therapeutic targets, network modules, and coexpressed genes of Radix Rhei Et Rhizome intervention in cerebral infarction (CI), and to predict significant biological processes and pathways through network pharmacology. To explore the differential proteins of Radix Rhei Et Rhizome intervention in CI, conduct bioinformatics verification, and initially explain the possible therapeutic mechanism of Radix Rhei Et Rhizome intervention in CI through proteomics. Methods. The TCM database was used to predict the potential compounds of Radix Rhei Et Rhizome, and the PharmMapper was used to predict its potential targets. GeneCards and OMIM were used to search for CI-related genes. Cytoscape was used to construct a protein-protein interaction (PPI) network and to screen out core genes and detection network modules. Then, DAVID and Metascape were used for enrichment analysis. After that, in-depth analysis of the proteomics data was carried out to further explore the mechanism of Radix Rhei Et Rhizome intervention in CI. Results. (1) A total of 14 Radix Rhei Et Rhizome potential components and 425 potential targets were obtained. The core components include sennoside A, palmidin A, emodin, toralactone, and so on. The potential targets were combined with 297 CI genes to construct a PPI network. The targets shared by Radix Rhei Et Rhizome and CI include ALB, AKT1, MMP9, IGF1, CASP3, etc. The biological processes that Radix Rhei Et Rhizome may treat CI include platelet degranulation, cell migration, fibrinolysis, platelet activation, hypoxia, angiogenesis, endothelial cell apoptosis, coagulation, and neuronal apoptosis. The signaling pathways include Ras, PI3K-Akt, TNF, FoxO, HIF-1, and Rap1 signaling pathways. (2) Proteomics shows that the top 20 proteins in the differential protein PPI network were Syp, Syn1, Mbp, Gap43, Aif1, Camk2a, Syt1, Calm1, Calb1, Nsf, Nefl, Hspa5, Nefh, Ncam1, Dcx, Unc13a, Mapk1, Syt2, Dnm1, and Cltc. Differential protein enrichment results show that these proteins may be related to synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, synaptic vesicle endocytosis, axon guidance, calcium signaling pathway, and so on. Conclusion. This study combined network pharmacology and proteomics to explore the main material basis of Radix Rhei Et Rhizome for the treatment of CI such as sennoside A, palmidin A, emodin, and toralactone. The mechanism may be related to the regulation of biological processes (such as synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, and synaptic vesicle endocytosis) and signaling pathways (such as Ras, PI3K-Akt, TNF, FoxO, HIF-1, Rap1, and axon guidance).
1. Introduction
Cerebral infarction (CI) or ischemic stroke (IS) mainly results from blood supply disturbances in local brain tissue areas, leading to necrosis of ischemic hypoxic lesions in the brain tissue, which results in the manifestation of corresponding neurological deficits [1]. Epidemiological studies have shown that stroke has become the disease with the highest mortality rate in China [2, 3]. CI is divided into cerebral thrombosis, cerebral embolism, and lacunar infarction according to the different pathogenesis. Among them, cerebral thrombosis is the most common type of CI, accounting for about 60% [4]. Timely thrombolysis to restore blood supply after infarction is the most important measure to save the ischemic area. Although reperfusion after ischemia can restore its function, ischemia-reperfusion injury makes the irreversible damage to the brain tissue after the blood flow restored [5–7]. Cerebral ischemia-reperfusion injury (CIR) is mainly related to the formation of free radicals (oxygen and lipid free radicals), oxidative stress, energy metabolism disorders, apoptosis, excitatory amino acid toxicity, calcium overload, inflammation, and so on [6–9]. Currently, the preventive and therapeutic drugs for CIR include excitatory amino acid-regulating drugs, neurotrophic growth factors, free radical scavengers, nitric oxide synthase inhibitors, intracellular calcium overload inhibitors, and natural plant active compounds (flavonoids, saponins, polysaccharides) [8, 10–13]. Of particular importance is that natural plant active compounds are becoming potential CIR drugs.
Radix Rhei Et Rhizome is an important part of the traditional Chinese medicine (TCM) formulas for the treatment of CI in the acute phase, which has a long history of medicinal use [14–18]. Modern medical research proves that rhubarb aglycones have significant protective effects on ischemic brain tissue: it can maintain the integrity of the blood-brain barrier, reduce inflammation, inhibit apoptosis, and protect nerves [15–19]. However, its specific mechanism is still unclear. Therefore, this research hopes to propose a new method to analyze the regulatory mechanism of Radix Rhei Et Rhizome on CI biological networks. The development of high-throughput omics and chemoinformatics has given the opportunity to analyze the mechanisms of natural plant components for disease treatment [20–24]. Therefore, based on previous research, this study will integrate proteomics and chemoinformatics strategies to further explore the molecular mechanism of Radix Rhei Et Rhizome’s intervention in CI and provide reference information for new drug development and its clinical application. The idea and process of this research are shown in Figure 1.
... is is particularly suitable for studying the role of TCM multi-componentsmulti-targets and is conducive to revealing its complex mechanism [16][17][18][19]. erefore, this study will combine the methods of experimental pharmacology and network pharmacology to explore the therapeutic mechanism of MSHC on T2DM. ...
... for network construction [29]. e networks were analyzed by the plugin molecular complex detection (MCODE) to obtain cluster [14,15,[17][18][19]. MCODE can be used to discover closely related regions in the PPI network, and these regions may represent molecular complexes. ...
Objective:
To explore the mechanism of modified Huanglian Maidong decoction (Maidong-Sanqi-Huanglian Compounds, MSHCs) intervention in type 2 diabetes mellitus (T2DM).
Method:
This study used PubChem and SciFinder to collect the molecular structure of MSHCs, used PharmMapper to predict the potential targets of MSHC, and combined them with the T2DM gene to construct MSHC-T2DM protein-protein interaction (PPI) network. The plugin MCODE in Cytoscape 3.7.1 was then used to perform cluster analysis on the MSHC-T2DM PPI network. The genes and targets were input into DAVID for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the therapeutic effect of MSHC on T2DM.
Results:
Several T2DM-related targets, clusters, signaling pathways, and biological processes are found. The experimental results showed that compared with the blank group, the content of fasting blood glucose (FBG) in the model group was higher (P < 0.01). Compared with the model group, the content of FBG decreased and the insulin level increased in the MSHC medium-dose (0.15 g/kg) and high-dose (0.45 g/kg) groups and metformin group after 4 weeks of drug administration (P < 0.05). MSHC can also improve blood liquid levels and inflammatory factor levels (P < 0.05).
Conclusion:
MSHC may achieve therapeutic effects through regulating the T2DM-related targets, biological processes, and pathways, such as insulin resistance, energy metabolism, oxidative stress, and inflammation, found in this research.
... However, the mechanism of HCC in treating cerebral ischemia is still not fully explained. Systematic pharmacology is an emerging discipline based on the intersection and integration of multidisciplinary technologies such as classic pharmacology, computer technology, bioinformatics, and network pharmacology, which systematically studies the interactions between drugs and the human body at multiple levels, including molecules, cells, organs, and networks Bao et al., 2019;Yang et al., 2019a;Yang et al., 2019b). Our previous research used systematic pharmacological strategies to reveal the mechanism of Chinese medicine formula in the treatment of complex diseases in the fields of oncology and cardiovascular Bao et al., 2019;Yang et al., 2019a;Yang et al., 2019b). ...
... Systematic pharmacology is an emerging discipline based on the intersection and integration of multidisciplinary technologies such as classic pharmacology, computer technology, bioinformatics, and network pharmacology, which systematically studies the interactions between drugs and the human body at multiple levels, including molecules, cells, organs, and networks Bao et al., 2019;Yang et al., 2019a;Yang et al., 2019b). Our previous research used systematic pharmacological strategies to reveal the mechanism of Chinese medicine formula in the treatment of complex diseases in the fields of oncology and cardiovascular Bao et al., 2019;Yang et al., 2019a;Yang et al., 2019b). Therefore, this study hopes to reveal the complex mechanism of HCC through a systematic pharmacology strategy (integrating network pharmacology experimental pharmacology). ...
... The networks were analyzed by the plugin MCODE to obtain cluster. The definition and the methodology of acquisition of clusters were described in our previous work Bao et al., 2019;Yang et al., 2019a;Yang et al., 2019b), such as "Exploring the Pharmacological Mechanism of Quercetin-Resveratrol Combination for Polycystic Ovary Syndrome: A Systematic Pharmacological Strategy-Based Research" (Yang et al., 2019a) and "Uncovering the Pharmacological Mechanism of Astragalus Salvia Compound on Pregnancy-Induced Hypertension Syndrome by a Network Pharmacology Approach" . ...
Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.
Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.
Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).
Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.
... Our previous research successfully used systematic biological methods (such as network pharmacology and systematic pharmacology) to explore the mechanism of herbal formulae for treating diseases. [19][20][21][22][23] Hence, this study will explore the mechanism of DSYM regulating AS's biological network by an integrated systematic biological and proteomics strategies, and provide new ideas for drug development. ...
... 29 The compounds with OB ≥ 30%, Caco-2> −0.4 and DL ≥ 0.18 were considered to be orally absorbable and pharmacologically active (namely, potential compounds). [19][20][21][22][23][24][25][26][27]29 Due to the limitation of predicting potential components based on pharmacokinetic parameters only, 30 in order to avoid omission of components, we searched a large number of literatures to supplement orally absorbable compounds with bioactive. Finally, after searching, a total of 34 components were added from the reference. ...
... 48 The definition and the methodology of acquisition of clusters were described in our previous work. [19][20][21][22][23] ...
This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.
... The network pharmacology strategy provides new opportunities for revealing complex traditional Chinese medicine prescriptions [20][21][22][23][24]. Traditional Chinese Medicine (TCM) treats diseases following a holistic view. ...
... Network pharmacology is an important part of systematic biology. Its holistic, systemic, and drug-oriented interactions are in line with the basic characteristics of TCM, which is a new discipline that reveals the regulatory effects of compound drugs on the bio-logical network of the body from a system level, and has established a bridge for studying the relationship between TCM and modern pharmacology [20][21][22][23][24][25]. Therefore, this study hopes to explore the molecular network of HDC intervention in DCM through a network pharmacology strategy. ...
Objective. To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy. Methods. Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC’s active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry. Results. A total of 176 of HDC’s active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P
... Systematic pharmacological studies have revealed the biological networks in which drugs work. The integration strategy of network biology and multidirectional pharmacology is conducive to expanding the available drug target space and is expected to become one of the new strategies for drug discovery, especially in the field of research and development of Chinese medicine formulae [14][15][16][17][18]. Our previous research successfully analyzed the molecular mechanisms and pharmacodynamic components of traditional Chinese medicine in the fields of cardiovascular and cerebrovascular diseases, tumors, and complex endocrine diseases through the chemical informatics and complex pharmacology methodological strategies [17,18]. ...
... The integration strategy of network biology and multidirectional pharmacology is conducive to expanding the available drug target space and is expected to become one of the new strategies for drug discovery, especially in the field of research and development of Chinese medicine formulae [14][15][16][17][18]. Our previous research successfully analyzed the molecular mechanisms and pharmacodynamic components of traditional Chinese medicine in the fields of cardiovascular and cerebrovascular diseases, tumors, and complex endocrine diseases through the chemical informatics and complex pharmacology methodological strategies [17,18]. Therefore, in this research, we hope to explore the biological mechanism of endoplasmic reticulum stress after HCC intervention in IS by systematic pharmacology. ...
... To verify the quality of HCC, we qualitatively verified three [22] were utilized to collect all compounds of Hedysarum multijugum Maxim., Chuanxiong rhizoma, Phere-tima, and Bombyx batryticatus. Oral bioavailability (OB), drug-likeness (DL), and Caco-2 permeability were utilized to identify the potential bioactive compounds of HCC [17,18,[23][24][25][26]. The compounds that meet the standards of OB ≥ 30 %,Caco-2 > −0:4, and DL ≥ 0:18 were regarded as oral absorbable compounds with biologically active [17,18,[23][24][25][26]. ...
Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats (P
