Current computer-aided drug design最新文献

{"title":"Accelerating Rheumatoid Arthritis Drug Repurposing: A Computational Approach.","authors":"Muskan Gupta, Tuhin Mukherjee, Satyajit Mohanty","doi":"10.2174/0115734099326517240801035901","DOIUrl":"10.2174/0115734099326517240801035901","url":null,"abstract":"","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"125-128"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Exploration of Isatin Derivatives for InhA Inhibition in Tuberculosis: Molecular Docking, MD Simulations and ADMET Insights.","authors":"Vaishali Pavalbhai Patel, Rati Kailash Prasad Tripathi, Abhay Dharamsi","doi":"10.2174/0115734099333313240909103833","DOIUrl":"10.2174/0115734099333313240909103833","url":null,"abstract":"<p><strong>Background: </strong>Anti-tubercular drug discovery is a critical research area aimed at addressing the global health burden imposed by <i>Mycobacterium tuberculosis</i>. Nowadays, computational techniques have increased the likelihood of drug development compared to traditional, labor-intensive, and time-consuming drug design approaches. The pivotal goal of drug design is to identify compounds capable of selectively targeting protein, thereby disrupting its enzymatic activity. InhA, or NADH-dependent enoyl-acyl carrier protein reductase, stands at the forefront of targeted approaches in the battle against TB. Isatin derivatives have garnered interest for their diverse pharmacological activities.</p><p><strong>Objective: </strong>To identify novel isatin derivatives that could serve as potential chemical templates for anti-TB drug discovery by targeting InhA.</p><p><strong>Methods: </strong>The present work utilized various computational approaches, including molecular docking, binding free energy calculations, and conformational alignment studies to investigate the binding mode and interactions of carefully selected dataset of 88 isatin derivatives within InhA active site. Study also employed MD simulations of the most promising molecule to check the stability of the protein-ligand complex and <i>in-silico</i> ADMET profiling of the top compounds to predict their pharmacokinetic and toxicity properties.</p><p><strong>Results: </strong>Results provided insights into the structural features contributing to InhA inhibition, assessing overall drug-like characteristics of isatin derivatives and identified compound 48 (BA= -10.4 kcal mol^-1) with potential for further optimization. MD simulation analysis revealed that compound 48 binds firmly within the InhA protein, exhibiting minimal conformational fluctuations and enhanced stability.</p><p><strong>Conclusion: </strong>Considering the aforementioned, isatin derivatives represents a novel framework for creating targeted InhA inhibitors during anti-<i>TB</i> therapy. However, experimental validations and in-depth analyses are crucial to confirm efficacy and safety of these derivatives as potential InhA inhibitors for TB treatment.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"226-254"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms Underlying the Attenuating Effects of Bugantang on Liver Fibrosis based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.","authors":"Taojing Zhang, Jia Chang, Zengle Zheng, Guobi Chen, Yiping Wu, Jinxiang Xiang, Jing Chen","doi":"10.2174/0115734099335133241030110644","DOIUrl":"https://doi.org/10.2174/0115734099335133241030110644","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis, a chronic liver disease, threatens people's health, increases the burden of healthcare, and currently lacks effective treatment measures. Bugantang (BGT) is a traditional Chinese herbal prescription from Jin Kui Yi with promising potential for treating liver fibrosis. Despite this potential, the efficacy and mechanism for treating liver fibrosis remain unclear.</p><p><strong>Objective: </strong>To primarily prove the efficacy, predict the active components of BGT, and explore the mechanism of BGT on liver fibrosis.</p><p><strong>Methods: </strong>The liver condition of CCL4-induced mice was examined using hematoxylin and eosin staining. The targets and active compounds of BGT were sourced from HERB and TCMSP databases, while the targets related to liver fibrosis were acquired from DisGeNET, Gene Expression Omnibus, and GeneCards databases. The core targets were identified, and the network of protein-protein interactions was established. KEGG and GO analyses were performed on DAVID. Molecular docking and molecular dynamics simulations assessed the active components' interactions with potential targets.</p><p><strong>Results: </strong>A total of 215 targets and 152 active compounds were identified for BGT. The network analysis identified kaempferol, quercetin, 2-(2,4-dihydroxyphenyl)-7-hydroxy-4Hchromen- 4-one, sitosterol, naringenin, adenosine, plo, and beta-sitosterol as potential key compounds, and AKT1, MMP9, SRC, TNF, ESR1, NF-κB, and PPARG as potential key targets. KEGG and GO analyses revealed that the therapeutic effect of BGT on liver fibrosis may be associated with the PI3K-AKT and MAPK signaling pathways, as well as cell apoptosis, protein phosphorylation, and inflammation. Molecular docking demonstrated high-affinity binding of the identified targets to the active compounds. Additionally, molecular dynamics simulation further confirmed that the bindings of AKT1-beta-sitosterol and MMP9-quercetin exhibited good stability.</p><p><strong>Conclusions: </strong>The potential of BGT in alleviating liver fibrosis may be attributed to a combination of various active compounds, targets, and pathways. These results could support the use of BGT in treating liver fibrosis and facilitate the development of new drug candidates for this condition.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology and In Vivo Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration.","authors":"Hui Jin, Huaiyu Ma, Jie Wu, Ruizhe Wu, Haoran Xu, Weixing Chen, Linghui Li, Jingqi Zeng, Fan Wang","doi":"10.2174/0115734099356426241119051916","DOIUrl":"https://doi.org/10.2174/0115734099356426241119051916","url":null,"abstract":"<p><strong>Objective: </strong>The Qing'e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.</p><p><strong>Methods: </strong>Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.</p><p><strong>Results: </strong>We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.</p><p><strong>Conclusion: </strong>The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xuebijing Exerts Protective Effects on Myocardial Cells by Upregulating TRIM16 and Inhibiting Oxidative Stress and Apoptosis.","authors":"Xiaoyan Meng, Xinming Yan, Peng Xue, Zhaoqing Xi","doi":"10.2174/0115734099318323241122184120","DOIUrl":"https://doi.org/10.2174/0115734099318323241122184120","url":null,"abstract":"<p><strong>Objective: </strong>This study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury.</p><p><strong>Methods: </strong>We investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC).</p><p><strong>Results: </strong>First, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly upregulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16.</p><p><strong>Conclusion: </strong>Our comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Mechanism of Alpinia officinarum Hance in the Improvement of Insulin Resistance through Network Pharmacology, Molecular Docking and in vitro Experimental Verification.","authors":"Mingyan Zhou, Xiuxia Lian, Xuguang Zhang, Jian Xu, Junqing Zhang","doi":"10.2174/0115734099325919241025023026","DOIUrl":"https://doi.org/10.2174/0115734099325919241025023026","url":null,"abstract":"<p><strong>Background: </strong>Research has elucidated that the pathophysiological underpinnings of non-alcoholic fatty liver disease and type 2 diabetes mellitus are intrinsically linked to insulin resistance (IR). However, there are currently no pharmacotherapies specifically approved for combating IR. Although Alpinia officinarum Hance (A. officinarum) can ameliorate diabetes, the detailed molecular mechanism through which it influences IR has not been fully clarified.</p><p><strong>Aims: </strong>To predict the active components of A. officinarum and determine the mechanism by which A. officinarum affects IR.</p><p><strong>Methods: </strong>The active compounds and molecular mechanism underlying the improvement of IR by A. officinarum were predicted via network pharmacology and molecular docking. To further substantiate these predictions, an in vitro model of IR was induced in HepG2 cells using high glucose concentrations. Cytotoxicity and oxidative stress levels were evaluated using Cell Counting Kit-8, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assay kits. The putative molecular mechanisms were corroborated through Western blot and RT-PCR analyses.</p><p><strong>Results: </strong>Fourteen principal active components in A. officinarum, 133 potential anti-IR gene targets, and the top five targets with degree values were ALB, AKT1, TNF, IL6, and VEGFA. A. officinarum was posited to exert its pharmacological effects on IR through mechanisms involving lipid and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, the PI3K-AKT signaling pathway, fluid shear stress, and atherosclerosis. Intriguingly, network pharmacology analysis highlighted (4E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3- one (A14) as the most active compound. Molecular docking studies further confirmed that A14 has a strong binding affinity for the main targets of PI3K, AKT, and Nrf2. The experiments demonstrated that A14 significantly diminished the ROS and MDA levels while augmenting the SOD activity. Moreover, A14 was found to elevate the protein expression of PI3K, AKT, Nrf2, and HO-1, and increase the mRNA levels of these targets as well as NQO1.</p><p><strong>Conclusion: </strong>A. officinarum could play a therapeutic role in IR through multiple components, targets, and pathways. The most active component of A. officinarum responsible for combating IR is A14, which has the ability to regulate oxidative stress in IR-HepG2 cells by activating the PI3K/AKT/Nrf2 pathway. These findings suggest a potential pharmacological intervention strategy for the treatment of IR.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Biological Evaluation, Molecular Docking Studies and ADMET Prediction of Oxindole-Based Hybrids for the Treatment of Tuberculosis.","authors":"Vaishali Pavalbhai Patel, Rati Kailash Prasad Tripathi, Snigdha Das Mandal","doi":"10.2174/0115734099353857241022102426","DOIUrl":"https://doi.org/10.2174/0115734099353857241022102426","url":null,"abstract":"<p><strong>Introduction: </strong>With a projected mortality toll of 1.4 million in 2019, tuberculosis (TB) continues to be a significant public health concern around the world. Studies of novel treatments are required due to decreased bioavailability, increased toxicity, increased side effects, and resistance of several first- and second-line TB therapies, including isoniazid and ethionamide.</p><p><strong>Methods: </strong>This study reports the synthesis of oxindole-based hybrids as potent InhA inhibitors targeting Mycobacterium tuberculosis. The synthesized compounds (5a-5e and 8a-8c) were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis and nontuberculous mycobacteria (NTMs), viz. M. abscessus (ATCC 19977), M. fortuitum (ATCC 6841), and M. chelonae (ATCC 35752) using the Microplate Alamar Blue Assay (MABA). Molecular docking studies were performed using AutoDock Vina to explore the binding interactions of these compounds with the InhA enzyme (PDB: 2NSD). Additionally, biochemical and histopathological studies were conducted to assess the hepatotoxicity of the lead compounds. Insilico molecular properties and ADMET properties of the synthesized compounds were predicted using SwissADME and Deep-PK online tools to assess their drug-likeness.</p><p><strong>Results: </strong>Among the tested compounds, 8b exhibited significant anti-mycobacterial activity with a minimum inhibitory concentration (MIC = 1 μg/mL) comparable to the reference drug ethambutol. Further, the compound demonstrated a binding affinity and orientation similar to the reference inhibitor 4PI, indicating its potential as a potent InhA inhibitor, and was found to be stabilized within the binding pocket of InhA through H-bonding, hydrophobic and van der Waal's interactions. Besides, the compounds hepatotoxicity assessment studies depicted that 8b showed no significant liver dysfunction or damage to liver tissues. Additionally, 8b adhered to Lipinski's rule of five and Veber's rule, displaying favourable pharmacokinetic and drug-like properties, including high human intestinal absorption, distribution, and acceptable metabolic stability and excretion.</p><p><strong>Conclusion: </strong>Compound 8b emerged as a promising candidate for further optimization and development as a therapeutic agent for tuberculosis, offering a new avenue for tackling tuberculosis.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Novel Inhibitors for Dengue NS2B-NS3 Protease by Combining Topological similarity, Molecular Dynamics, MMGBSA and SiteMap Analysis.","authors":"Sheikh Murtuja, Mohd Usman Mohd Siddique, Kumar Pratyush Srivastava, Yogeeta O Agarwal, Sakshi Wagh, Sabina Yasmin, Azim Ansari, Mohd Sayeed Shaikh, Md Saquib Hasnain, Sameer N Goyal","doi":"10.2174/0115734099329789240905141013","DOIUrl":"https://doi.org/10.2174/0115734099329789240905141013","url":null,"abstract":"<p><strong>Introduction: </strong>DENV NS2B-NS3 protease inhibitors were designed based upon the reference molecule, 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl) benzenesulfonamide, reported by our team with the aim to optimize lead compound via rational approach. Top five best scoring molecules with zinc ids ZINC23504872, ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613 bearing 'pyrimidin-4(3H)-one' basic scaffold have been identified as a promising candidate against DENV protease enzyme.</p><p><strong>Methods: </strong>The shape and electrostatic complementary between identified HITs and reference molecules were found to be Tanimotoshape 0.453, 0.690, 0.680, 0.685 & 0.672 respectively and Tanimotoelectrostatic 0.211, 0.211, 0.441, 0.442, 0.442 and 0.442 respectively. The molecular docking studies suggested that the identified HITs displayed the good interactions with active site residues and lower binding energies. The stability of docked complexes was assessed by MD simulations studies. The RMSD values of protein backbone (1.6779, 3.1563, 3.3634, 3.3893 & 3.0960 Å) and protein backbone RMSF values (1.0126, 1.0834, 1.0890, 0.9974 & 1.0080 Å respectively) for all top five HITs were stable and molecules did not fluctuate from the active pocket during entire 100ns MD run.</p><p><strong>Results: </strong>The druggability Dscore below 1 indicate the tightly binding of ligand at the active site. Dscore for ZINC23504872 was found to be 1.084 while for the second class of compounds ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613, 0.503, 0.484, 0.487 and 0.501 Dscores were observed. In-silico ADMET calculations suggested that all five HITs were possessed the drug likeliness properties and did not violate the Lipinski's rule of five.</p><p><strong>Conclusion: </strong>Summing up, these in-silico generated data suggested that the identified molecules bearing pyrimidin-4(3H)-one would be promising scaffold for DENV protease inhibitors. However, experimental results are needed to prove the obtained results.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Two GSK3β Inhibitors from Sophora flavescens Ait. using Structure-based Virtual Screening and Bioactivity Evaluation.","authors":"Dabo Pan, Yong Zeng, Dewen Jiang, Yonghao Zhang, Mingkai Wu, Yaxuan Huang, Minzhen Han, Xiao-Jie Jin","doi":"10.2174/0115734099321878241011104241","DOIUrl":"https://doi.org/10.2174/0115734099321878241011104241","url":null,"abstract":"<p><strong>Objective: </strong>Kushen (Sophora flavescens Ait.) has a long history of medicinal use in China due to its medicinal values, such as antibacterial, antiviral, and anti-inflammatory. Rapid discovery of the components and the medicinal effects exerted by Kushen will help elucidate the science of Kushen in curing diseases. GSK3β (glycogen synthase kinase-3 beta) is a protein kinase with a wide range of physiological functions, such as antibacterial, antiviral, and anti-inflammatory. The discovery of inhibitors targeting GSK3β from Kushen was not only helpful for the rapid discovery of the components responsible for the efficacy of Kushen but also important for the development of novel drugs.</p><p><strong>Methods: </strong>In this study, the chemical composition of Kushen was extracted from the TMSCP database. Molecular docking, GSK3β enzyme assay, and molecular dynamics simulations were used to discover the GSK3β inhibitors from the chemical composition of Kushen.</p><p><strong>Results: </strong>A total of 113 chemical compositions of Kushen were extracted from the TMSCP database. Molecular docking indicated that 15 chemical compositions of Kushen scored better than -8 kcal/mol against GSK3β. GSK3β enzyme assay demonstrated several inhibitory activities of kushenol I and kushenol F with IC50 values of 7.53 ± 2.55 μM and 4.96 ± 1.29 μM, respectively. Molecular dynamics simulations were used to reveal the interactions of kushenol I and kushenol F with GSK3β from structural and energetic perspectives.</p><p><strong>Conclusion: </strong>Kushenol I and kushenol F could be the material basis for the antibacterial, antiviral, and anti-inflammatory properties of Kushen.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Ameliorates High-fat-induced Insulin Resistance in HepG2 Cells by Modulating PPARs Signaling Pathway.","authors":"Lingxiao Zhang, Chenghao Yang, Xinyue Ding, Hui Zhang, Yuling Luan, Yueer Tang, Zongjun Liu","doi":"10.2174/0115734099330183241008071642","DOIUrl":"https://doi.org/10.2174/0115734099330183241008071642","url":null,"abstract":"<p><strong>Background: </strong>Berberine (BBR), also known as berberine hydrochloride, was isolated from the rhizomes of the Coptis chinensis. Studies have reported that BBR plays an important role in glycolipid metabolism, including insulin (IR). The targets, and molecular mechanisms of BBR against hyperlipid-induced IR is worthy to be further studied.</p><p><strong>Material and methods: </strong>The related targets of BBR were identified via Pharmmapper database and relevant targets of diabetes were obtained through GeneCards and Online Mendelian Inheritance in Man (OMIM) database. The common targets were employed with the STRING database and visualized with the protein-protein interactions (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore the biological progress and pathways. In vitro, human hepatocellular carcinomas (HepG2) cell was used as experimental cell line, and an insulin resistant HepG2 cell model (IR-HepG2) was constructed using free fatty acid induction. After intervention with BBR, glucose consumption and uptake in HepG2 cells were observed. Molecular docking was used to test the interaction between BBR and key targets, and real-time fluorescence quantitative PCR was used to detect the regulatory effect of BBR on related targets.</p><p><strong>Results: </strong>262 overlapped targets were extracted from BBR and diabetes. In the KEGG enrichment analysis, the peroxisome proliferator activated receptor (PPAR) signaling pathway was included. In vitro experiments, BBR can significantly increase sugar consumption and uptake in IR HepG2 cells, while PPAR inhibitors can weaken the effect of BBR on IR-HepG2.</p><p><strong>Conclusion: </strong>The PPAR signaling pathway is one of the important pathways for BBR to improve high-fat-induced insulin resistance in HepG2 cells.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}