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1.
Cancer Research and Clinic ; (6): 66-69, 2022.
Article in Chinese | WPRIM | ID: wpr-934629

ABSTRACT

Lung cancer is the main cause of cancer-related deaths, and its morbidity and mortality is the highest, which seriously affects patients' survival time and quality of life. To develop new targets of tumor cells and expand the beneficiary population of lung cancer patients have become a hot and difficult research topic in recent years. RNA binding protein human antigen R (HuR) plays an important role in the development and progression of lung cancer. It can affect the transcription, translation and synthesis of multiple genes, proteins and molecules of lung cancer cells by binding to specific mRNA in lung cancer cells, and promote proliferation, differentiation and apoptosis of lung cancer cells. HuR is of great significance in molecular diagnosis, treatment and prognosis of lung cancer. This article will review the biological characteristics of HuR and research progress of its interaction with HuR-related regulatory factors in lung cancer based on relevant domestic and foreign literatures.

2.
Chinese Journal of Geriatrics ; (12): 104-107, 2022.
Article in Chinese | WPRIM | ID: wpr-933042

ABSTRACT

DNA damage is one of the research hotspots in the field of aging and related diseases, because it can cause cell cycle arrest and apoptosis, accelerate the body's rate of aging and increase the risk of aging-related diseases.This review will summarize the mechanisms of DNA damage in cells, animal models and individuals and its associations with aging and aging-related diseases, including cancer, cardiovascular disease, Alzheimer's disease and premature aging syndromes.We aim to provide a theoretical framework for anti-aging research and clinical intervention in the treatment of aging-related diseases.

3.
Article in Chinese | WPRIM | ID: wpr-932785

ABSTRACT

Severe acute pancreatitis (SAP) is closely related to intestinal mucosal barrier dysfunction, in which intestinal epithelial mechanical barrier injury is the structural basis of SAP-related intestinal mucosal dysfunction. Among the molecular mechanisms of injury factors, inflammatory mediators and cytokines, produced by SAP waterfall inflammation, are the main factors of intestinal mucosal barrier injury. This article briefly describes the effects of SAP on intestinal mechanical barrier injury and its molecular mechanism in order to provide ideas for the treatment of SAP.

4.
Article in Chinese | WPRIM | ID: wpr-940678

ABSTRACT

ObjectiveTo reveal the pharmacological mechanisms of astragaloside Ⅳ(AS-Ⅳ)in treating diabetic retinopathy based on network pharmacology and molecular docking and to provide reference for new drug development and mechanism research. MethodPotential targets of AS-Ⅳ were obtained from SwissTargetPrediction and Targetnet. The targets of diabetic retinopathy were screened using GeneCards,Online Mendelian Inheritance in Man(OMIM) and Therapeutic Target Database. The targets of AS-Ⅳ and diabetic retinopathy were intersected by Venny 2.1.0. STRING platform and Cytoscape 3.7.2 were used to construct protein-protein interaction(PPI) network and screen core targets, respectively. Then,Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Furthermore,the binding affinity of AS-Ⅳ to key target receptors was assessed by molecular docking with Autodock Vina, and the key target signaling transduction pathway was ResultA total of 56 intersected targets of AS-Ⅳ and diabetic retinopathy were found,and the top five key targets were obtained through PPI network analysis:protein kinase B(Akt)1,vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),Src and signal transducer and activator of transcription 3(STAT3). Molecular docking verified the strong binding affinity of AS-Ⅳ to the five key target receptors. In addition,in vitro tests have been confirmed that AS-Ⅳ attenuated high glucose-induced injury in human retinal pigment epithelial cell line ARPE-19 by regulating Akt/Nrf2/HO-1 and Akt/glycogen synthase kinase-3β(GSK-3β)signaling pathways. ConclusionThere was a significant overlap in the targets of AS-Ⅳ and diabetic retinopathy. The key targets and pathways may reveal the main pharmacological mechanism of AS-Ⅳ in the treatment of diabetic retinopathy.

5.
Article in Chinese | WPRIM | ID: wpr-940535

ABSTRACT

ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information (NCBI), and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. Finally, AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out, including β-sitosterol, sesamin, and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved, such as protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), hypoxia inducible factor-1A (HIF-1A), proto-oncogene tyrosine-protein kinase (SRC), and matrix metalloproteinase-9 (MMP-9). Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism, nucleic acid transcription, and metabolic enzyme pathway, and 28 key KEGG pathways, including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component, multi-target, and multi-pathway interactions, thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.

6.
Article in Chinese | WPRIM | ID: wpr-940478

ABSTRACT

Andrographolide, a diterpene lactone, is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata (Burm.f.)Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation, bacteriostat, anti-virus, anti-tumor, protecting liver, promoting the function of gallbladder, and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific, it can inhibit nuclear factor-κB (NF-κB), signal transduction and activator of transcription 3 (STAT3), and other signaling pathways, reduce the synthesis and release of downstream inflammatory mediators, and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time, it suppresses a variety of tumor cells by inhibiting tumor cell proliferation, blocking cell cycle, and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-κB, and secreted glycoprotein/β-catenin (Wnt/β-catenin). In addition, it can also alleviate diabetes by regulating glucose metabolism. According to related research, it often exerts pharmacological effects through multiple pathways and multiple targets, but the specific targets are unclear. Therefore, this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions, which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.

7.
Article in Chinese | WPRIM | ID: wpr-940462

ABSTRACT

ObjectiveTo explore the active ingredients, therapeutic targets, and relative signaling pathways of Tripterygium wilfordii in the treatment of triple negative breast cancer (TNBC) based on network pharmacology, and to verify the mechanism through in vitro cell model. MethodThe active ingredients of T. wilfordii were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of TNBC were obtained from DisGeNET and GeneCards. Venny was used to identify the potential therapeutic targets of T. wilfordii against TNBC. Protein-protein interaction (PPI) network was constructed with String database. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out with DAVID to predict the mechanisms of potential targets. The molecular docking between triptolide and key targets were performed with AutoDock Vina. The effect of triptolide (0, 5, 10, 20, 30, 40, 50, 60, 80 nmol·L-1) on the proliferation of MDA-MB-231 cells was determined through methyl thiazolyl tetrazolium (MTT) assay. The effect of triptolide (0, 12.5, 25, 50 nmol·L-1) on the apoptosis of MDA-MB-231 cells was detected with Hoechst 33342 staining. Western blot was performed to detect the effect of triptolide (0, 25, 50 nmol·L-1) on the expression levels of key targets. ResultT. wilfordii had 23 active ingredients related to 55 potential targets of TNBC. GO and KEGG enrichment revealed that the potential targets were associated with 103 biological processes, 15 cellular components, and 35 molecular functions, and were involved in 140 signaling pathways including atherosclerosis and apoptosis. The results of molecular docking demonstrated that triptolide could bind with the targets including threonine kinase 1 (Akt1), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (p53), transcription factor AP-1 (JUN), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), mitogen-activated protein kinase 8 (MAPK8), prostaglandin G/H synthase 2 (PTGS2), and Caspase-3. According to the results of MTT assay, triptolide (20, 30, 40, 50, 60, 80 nmol·L-1) inhibited the proliferation of MDA-MB-231 cells compared with blank control (P<0.05, P<0.01). Hoechst 33342 staining showed that triptolide (12, 25, 50 nmol·L-1) induced the apoptosis of MDA-MB-231 cells compared with black control (P<0.05, P<0.01). Western blot showcased that 50 nmol·L-1 triptolide down-regulated the relative expression levels of p-Akt, TNF-α, and VEGFA, while 25 and 50 nmol·L-1 triptolide up-regulated the relative expression level of p53 in a dose-dependent manner compared with the blank control (P<0.05, P<0.01). ConclusionT. wilfordii has multiple ingredients, targets, and pathways in the treatment of TNBC. It may regulate p53, VEGFA, TNF-α and other key targets to induce cell apoptosis and suppress angiogenesis and inflammatory response, which provides a scientific basis for the further investigation and clinical application of T. wilfordii.

8.
Article in Chinese | WPRIM | ID: wpr-940419

ABSTRACT

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules (DZSM) on chronic cerebral hypoperfusion (CCH), network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group, model group, ginaton group (48 mg·kg-1), DZSM low- and high-dose groups (0.040 5, 0.162 g·kg-1). The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem, GeneCards, Metascape and other databases were used for targets collection and enrichment analysis. Besides, the association of ingredients targets of DZSM with disease targets of CCH, core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment, the crossing times, time spent in the target quadrant, movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, cytokine-cytokine receptor interaction, tumor necrosis factor (TNF) signaling pathway, blood circulation, angiogenesis, extracellular matrix and other related biological processes and pathways, and acting as targets such as interleukin-6 (IL-6), TNF, insulin-like growth factor 1 (IGF1), vascular endothelial growth factor A (VEGFA), epidermal growth factor (EGF). The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH, and its multi-component, multi-pathway, multi-target mechanism is also revealed, which provides a basis for further study of the mechanism.

9.
Article in Chinese | WPRIM | ID: wpr-940418

ABSTRACT

Sleep plays an important role in energy balance. As reported, sleep disorder is an important risk factor for metabolic diseases. Controlling the relationship between energy metabolism and sleep can affect sleep homeostasis and body metabolic rate. Chinese medicine, with remarkable curative effects in the prevention and treatment of insomnia, has the characteristics of green, safety, and few side effects, and attracts extensive attention of scholars in the world. In recent years, remarkable progress has been made in the research on the mechanism of Chinese medicine in interfering with sleep. This paper reviewed the research progress of mind-tranquilizing Chinese medicines, such as compounds (pterostilbene), Chinese medicinal drugs (Ziziphi Spinosae Semen), and Chinese medicinal prescriptions (Jiaotaiwan, Suanzaoren tang, Tianwang Buxindan, Anmeidan, Banxia Houpotang, Qihuo decoction, Songyu Anshen prescriptions, and Shuxie Yihao prescriptions) in the treatment of sleep disorders by regulating energy metabolism. The findings revealed that Chinese medicine can intervene in the sleep deprivation model by affecting metabolism-related pathways such as material metabolism, mitochondrial function, oxidative stress and inflammatory response, appetite system, and biological clock system. In terms of frequency of use, the top drugs are Ziziphi Spinosae Semen, Poria, Schisandrae Chinensis Fructus, and Salviae Miltiorrhizae Radix et Rhizoma which affect heart and liver meridians to regulate blood circulation, ensure energy supply, and play the role of nourishing the heart and tranquilizing the mind. The present paper summarized the effects and mechanisms of Chinese medicine in the treatment of insomnia and other sleep disorders from the perspective of energy metabolism to provide references for further research and exploration of diseases in the future.

10.
Article in Chinese | WPRIM | ID: wpr-940371

ABSTRACT

Cardiovascular diseases, with high incidence and high mortality, belong to the category of "chest impediment and heart pain" in traditional Chinese medicine (TCM). Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills, one of the National Essential Drugs, is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease (Qi deficiency and blood stasis syndrome). This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi, activate blood, and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow, regulating immune functions, alleviating inflammation, detoxifying, and tranquilizing mind. Clinically, it is suitable for patients with angina pectoris caused by the lack of heart Yang, chest tightness, shortness of breath, palpitation, fear of cold for limbs and so on, especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports, this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets, location and links. Furthermore, we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research, aiming to provide data support and evidence for the clinical application of this medicine.

11.
Article in Chinese | WPRIM | ID: wpr-940190

ABSTRACT

ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology, and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards, therapeutic target database (TTD), online mendelian inheritance in man database (OMIM), and DrugBank, and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction (PPI) network was constructed by the STRING database, and the core targets were screened out based on topological parameter analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day (PD21) to the completion of restraint stress on the 97th postnatal day (PD97), the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone (CORT) in mice was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of protein kinase B (Akt1), mammalian target of rapamycin (mTOR), brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD95), and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR). ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder, with 161 drug-disease intersection targets. Among these intersection targets, core targets such as Akt1, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF), and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group, the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times, with significantly increased expression levels of p-Akt1, p-mTOR, BDNF, PSD95, and synaptophysin (Syp). ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder, and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1, IL-1β, IL-6, TNF, mTOR, and other core targets and modulating PI3K/Akt, MAPK, as well as neuroactive ligand-receptor interaction signal pathways.

12.
Article in Chinese | WPRIM | ID: wpr-940158

ABSTRACT

ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology, and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards, therapeutic target database (TTD), online mendelian inheritance in man database (OMIM), and DrugBank, and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction (PPI) network was constructed by the STRING database, and the core targets were screened out based on topological parameter analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day (PD21) to the completion of restraint stress on the 97th postnatal day (PD97), the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone (CORT) in mice was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of protein kinase B (Akt1), mammalian target of rapamycin (mTOR), brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD95), and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR). ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder, with 161 drug-disease intersection targets. Among these intersection targets, core targets such as Akt1, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF), and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group, the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times, with significantly increased expression levels of p-Akt1, p-mTOR, BDNF, PSD95, and synaptophysin (Syp). ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder, and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1, IL-1β, IL-6, TNF, mTOR, and other core targets and modulating PI3K/Akt, MAPK, as well as neuroactive ligand-receptor interaction signal pathways.

13.
Acta Pharmaceutica Sinica ; (12): 251-264, 2022.
Article in Chinese | WPRIM | ID: wpr-922939

ABSTRACT

Taking patient needs as the core and realizing clinical value as the guidance are the purpose and path of drug discovery. Whether the first-in-class drug or follow-on drugs are all to meet the demands of patients for drugs that are not treatable or more safe and effective. In order to realize clinical value, innovative drugs driven by basic biological research include three elements: understanding the molecular mechanism of pathogenesis; Grasping the microscopic features of the disease; clarifying the mechanism of action of drugs. The interrelation among the three is the translational medicine, and the medicinal chemistry plays an important role in the translations. That is, based on the results of basic research in biology/medicine, knowledge of the molecular mechanism of disease depends upon the establishment of various in vitro/in vivo models to find the key node and molecular regulation for the treatment of disease. Combined with the knowledge of gene deletion and variation, proteomics, epigenetics and other technologies, the molecular mechanism of disease provides multi-molecular information on the level of gene, proteins, enzymes, receptors, ion channels and signal transduction for molecular drug design. Insight into the microscopic characteristics of diseases would deepen the understanding of the molecular mechanism of the pathogenesis, as well as provide a feasible scientific path for the creation of new drugs. When the molecular mechanism of disease and the action mechanism of drugs are clarified, we have a deeper and wider understanding of the application of existing drugs (or active compounds), and may offer new ideas for drug design and application. In this translational process the medicinal chemistry plays a key role which requires medicinal chemists to break through the habitual thinking and working mode, backtracking (upstream) to basic research and its achievements and applying to the direction of creating new drugs in time, as well as paying attention to the clinical requirements (downstream) and implementing the specific content of the transformation process for the R&D of innovative drugs.

14.
Article in Chinese | WPRIM | ID: wpr-927996

ABSTRACT

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.


Subject(s)
Animals , Chemical and Drug Induced Liver Injury/etiology , Drugs, Chinese Herbal/toxicity , Ethanol , Medicine, Chinese Traditional , Molecular Docking Simulation , Rats , Reproducibility of Results
15.
Acta Pharmaceutica Sinica ; (12): 2087-2100, 2022.
Article in Chinese | WPRIM | ID: wpr-936568

ABSTRACT

Based on the research system of computer-aided drug design combined with complex network analysis, the potential mechanism of Dunhuang Dabupi Decoction in preventing and treating gastric cancer (GC) is analyzed, and the scientific connotation of its prescription rules is explored through the efficacy grouping. To study the effect of Dabupi Decoction freeze-dried powder solution on the proliferation activity of gastric cancer cells through cell experiments; the TCMSP and TCMID databases were used to collect the compound components of Dabupi Decoction. Swiss Target Prediction is used to predict potential targets of compounds. DrugBank, GeneCards, TTD, and DisGeNET were used to collect potential targets for gastric cancer. Analyze protein interactions of potential targets through the STRING database. DAVID database was used for KEGG enrichment analysis; Dabupi Decoction was divided into Wenzhong group (dried ginger), Yiqi group (ginseng, licorice, Atractylodes macrocephala), nourishing Yin group (Ophiopogon japonicus, Schisandra) and Jiangni group according to its efficacy characteristics. The inverse group (inula) has 4 functional compatibility groups. Cytoscape was used to construct a network of "medicinal flavor-potential active ingredient-key target" respectively, and the network was used to analyze the scientific connotation of the compatibility of efficacy groups. The Schrödinger software was used to verify the molecular docking of the core components and the core targets. The material basis of the Dabupi Decoction to prevent and treat gastric cancer was discovered through the combination of pattern analysis and combined free energy calculation. The core drug was analyzed from the perspective of dynamics through molecular dynamics simulation. Potential targets and representative potential compounds interact with each other. Cell experiments confirmed that Dabupitang freeze-dried powder solution can down-regulate the mitochondrial membrane potential of AGS gastric cancer cells, block the cell cycle in the G0/G1 phase (P < 0.05), and inhibit its proliferation (P < 0.05). The pathways enriched by the four functional groups contained in Dabupi Decoction are mainly distributed in the body's energy metabolism, inflammation-immune system regulation, and cycle-apoptotic functions. Each module is connected by a common target gene and has its own focus. The results of molecular docking showed that the compounds liquiritigenin, quercetin, kaempferol, isorhamnetin, methylophiopogonanone A, etc. may be the effective multi-target components of Dabupi Decoction. Estrogen receptor 1, androgen receptor, ATP-binding cassette superfamily G member 2, epidermal growth factor receptor, glycogen synthase kinase-3 beta and other targets have good affinity with each potential active compound, which may be a potential target of Dabupi Decoction for preventing and treating gastric cancer. Among them, kaempferol and the drug target EGFR not only have good binding ability, but also have good binding stability. This study is based on computer-aided drug design combined with complex network analysis strategies to initially reveal the material basis and molecular mechanism of Dabupi Decoction in the prevention and treatment of gastric cancer. It also explores the scientific connotation of Dabupi Decoction in the prevention and treatment of gastric cancer with different efficacy groups, and its clinical application provide chemical bioinformatics basis.

16.
Article in English | WPRIM | ID: wpr-929235

ABSTRACT

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.


Subject(s)
Computational Biology , Drugs, Chinese Herbal , Humans , Network Pharmacology , Phosphatidylinositol 3-Kinases , Urinary Bladder Neoplasms/genetics
17.
Rev. Soc. Bras. Med. Trop ; 55: e0349, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360814

ABSTRACT

ABSTRACT Polymyxin antibiotics are disfavored owing to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the increasing global prevalence of infections caused by multidrug-resistant (MDR) gram-negative bacteria, have renewed clinical interest in these polypeptide antibiotics. This review highlights the current information regarding the mechanisms of resistance to polymyxins and their molecular epidemiology. Knowledge of the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterial agents and rapid treatment choices.

18.
Article in Chinese | WPRIM | ID: wpr-908775

ABSTRACT

Vine tea has been used as an herbal tea by several ethnic minorities for hundreds of years in China.Flavonoids,a kind of indispensable component in a variety of nutraceutical,pharmaceutical and cosmetic applications,are identified to be the major metabolites and bioactive ingredients in vine tea.Interest-ingly,vine tea exhibits a wide range of significant bioactivities including anti-oxidant,anti-inflammatory,anti-tumor,antidiabetic,neuroprotective and other activities,but no toxicity.These bioactivities,to some extent,enrich the understanding about the role of vine tea in disease prevention and therapy.The health benefits of vine tea,particularly dihydromyricetin and myricetin,are widely investigated.However,there is currently no comprehensive review available on vine tea.Therefore,this report summarizes the most recent studies investigating bioactive constituents,pharmacological effects and possible mechanisms of vine tea,which will provide a better understanding about the health benefits and preclinical assessment of novel application of vine tea.

19.
Article in Chinese | WPRIM | ID: wpr-907401

ABSTRACT

Objective:To explore the role of casein kinase 1 gamma 2 (CSNK1G2) in the development and progression of head and neck squamous cell carcinoma (HNSC).Methods:Based on the Cancer Genome Atlas (TCGA), LinkedOmics and UALCAN were used to analyze the relationship among the mRNA expression of CSNK1G2, methylation, copy number variation and clinical indicators in HNSC, as well as to analysis CSNK1G2 related co-expression genes and proteins. The expression of CSNK1G2 in HNSC was verified by RT-qPCR experiments of clinical samples. Protein interaction network analysis on CSNK1G2 expression-related proteins was performed using STRING database.Results:UALCAN analysis showed that the expression of CSNK1G2 mRNA in HNSC was higher than that in normal tissues ( P<0.001), and the expression of CSNK1G2 mRNA was up-regulated in lower differentiation and Human Papilloma Virus (HPV)-positive HNSC (all P<0.05). But in HNSC with different pathological stages, different age stages and different lymph node metastasis stages (N stage), there was no difference in the amount of CSNK1G2 mRNA expression (all P>0.05). The RT-qPCR experiment confirmed the increased expression of CSNK1G2 mRNA in HNSC. LinkedOmincs analysis results showed that CSNK1G2 mRNA expression was positively correlated with CSNK1G2 copy number variation ( P<0.001) and negatively correlated with methylation ( P<0.001). Survival analysis results showed that high CSNK1G2 mRNA expression and copy number mutations predicted better survival ( P=0.033, P=0.015), while methylation levels were not associated with survival ( P=0.458). Gene set enrichment analysis results showed that CSNK1G2-related co-expression genes were mainly in DNA replication. The STRING's protein interaction network analysis results showed that TP53, CHEK1, and CHEK2 may be key proteins. These proteins are significantly associated with high expression levels of CSNK1G2. Conclusions:CSNK1G2 may cooperate with TP53, CHEK1 and CHEK2 related proteins to promote the development of HNSC and tumor proliferation, but does not affect the metastasis and spread of HNSC. An increase in the expression of CSNK1G2 in HNSC may indicate a better survival prognosis.

20.
Article in Chinese | WPRIM | ID: wpr-906502

ABSTRACT

There are certain limitations in the application of liver transplantation, resection and radiofrequency ablation for liver cancer. Therefore,specific and selective new drugs are needed to provide better treatment. Curcumin is a hydrophobic polyphenol with a wide range of activities,such as anti-inflammatory,antibacterial,anti-oxidant and anti-tumor properties. Its nano-preparation has stronger growth inhibition and pro-apoptosis effects on tumor cells. Literature retrieval found that curcumin's anti-liver cancer molecular mechanisms include inhibiting cell proliferation by regulating the expressions of relevant miR,glyoxalase 1(GLO1),CD133 and vascular endothelial growth factor (VEGF),inhibiting signal transducer and activator of transcription (STAT3) and YAP expression to induce cell apoptosis,regulating the heat shock protein 70 (HSP70)-Toll-like receptor 4 (TLR4) signaling pathway,Wnt/β-catenin and transforming growth factor(TGF)/epithelial-mesenchymal transition(EMT) pathways,nuclear factor-κB (NF-κB) signaling pathway and nuclear factor E2-related factor 2(Nrf2)/ Kelch-like ECH-related protein 1(Keap1) signaling pathway,inhibiting p38 mitogen-activated protein kinase (MAPK) phosphorylation,to reduce Lin28B expression,regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and inhibiting G protein-coupled receptors (GPR81)/hydroxycarboxylic acid receptor-1 (HCAR-1) expression to reverse transformation therapy resistance. Curcumin nano-preparation mainly includes polymer micelles,liposomes,loaded microbubbles,nanocapsules and nanoparticles. Curcumin is mainly delivered to liver cancer cells to rapidly release the drug,enhance the anti-liver cancer effect and reduce toxic and side effects in normal liver cells. The mechanisms include activation of DR5/Caspase-mediated exogenous apoptosis pathway and VEGF/VEGF receptors (VEGFRs) signaling pathway,loss of mitochondrial membrane potential and increase of intracellular reactive oxygen species (ROS). This paper summarizes the molecular mechanism of curcumin and its nano-preparation against liver cancer,in order to further define the molecular mechanism of liver cancer and provide a new reference for its clinical diagnosis and treatment.

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