Letters in Drug Design & Discovery最新文献

{"title":"Efficacy of Ginger, Cardamom, Purslane, Saffron and Cinnamon Consumption on Lipid Profile, Glycemic Control, Blood Pressure and Markers of Anthropometric and Inflammation in Metabolic Syndrome Patients: A Systematic Review and Network Meta-Analysis","authors":"Sajjad Salimi, Zahra Asgari, Tahereh Sadat Mousavi, Seyed Amir Karimi, Arezoo Hamidi, Shayan Mostafaei, Pardis Mohammadi Pour, Mohammad Hosein Farzaei","doi":"10.2174/0115701808270287240105092957","DOIUrl":"https://doi.org/10.2174/0115701808270287240105092957","url":null,"abstract":"Background:: Metabolic syndrome (MetS), also known as syndrome X or insulin resistance, is a complex disorder characterized by multiple risk factors. It is caused by insulin resistance, which is accompanied by abnormal accumulation and dysfunction of adipose tissue. Introduction:: Recently, several studies have evaluated the efficacy of herbs on MetS. The purpose of this meta-analysis is the comprehensive assessment of the impact of cardamom, cinnamon, saffron, purslane and ginger on the parameters of MetS in patients with MetS. Methods:: A systematic search was performed based on the English language reports of literature from databases including PubMed, Scopus, Cochrane, and Web of Science and 29 RCT (randomized clinical trial) studies were included in the meta-analysis. This meta-analysis was registered in PROSPERO. Results:: The results showed significant beneficial effects of cardamom on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and waist circumference (WC), cinnamon on diastolic blood pressure (DBP) and weight, ginger on fasting blood sugar (FBS), Hemoglobin A1c HbA1c and HOMA-IR and purslane on triglyceride (TG), total cholesterol (TC), body mass index (BMI) and FBS compared to the placebo; thus, they can be useful in the management of patients with MetS. Conclusion:: It is suggested that more RCT studies should be performed on the factors affecting the efficacy of these plants on the parameters of the MetS.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico Exploration of the Therapeutic Potential of Alkaloids as Anti-infective Agents","authors":"Nidhi Rani, Randhir Singh, Praveen Kumar, Aditiya Walia","doi":"10.2174/0115701808276535231212071700","DOIUrl":"https://doi.org/10.2174/0115701808276535231212071700","url":null,"abstract":"Background: Alkaloids are important phytoconstituents obtained from various plant sources. Methods: The main objective of the study was to evaluate the anti-infective potential of alkaloids against 14α-demethylase, transpeptidase, and omicron spike protein using molecular docking studies. The potential constituents were identified and an ADMET study was performed. Results: The study concluded that reserpine and tubocurarine exhibited potential activity against the three tested enzymes with good ADMET profile. Conclusion: Reserpine and tubocurarine can further be explored to attain new candidates as antiinfective agents.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crocin Potentiates Anti-tumor Properties of 5-FU by Regulating Cell Proliferation and Tumor Necrosis in Breast Cancer","authors":"Nastaran Rezaei, Abdulridha Mohammed Al-Asady, Milad Hashemzehi, Maryam Moradi Binabaj, Farzad Rahmani, Amir Avan, Moein Eskandari, Mohammad Jalili-Nik, Fereshteh Asgharzadeh, Seyedeh Elnaz Nazari, Mikhail Ryzhikov, Majid Khazaei, Seyed Mahdi Hassanian","doi":"10.2174/0115701808258032231204080133","DOIUrl":"https://doi.org/10.2174/0115701808258032231204080133","url":null,"abstract":"Introduction:: Breast cancer is one of the most prevalent malignancies among women around the world. Crocus sativus, a natural food coloring and flavoring, has potent anti-tumor properties. The aim of the current study was to investigate the therapeutic potential of crocin, the main pharmacological active component of saffron, either alone or in combination with the standard chemotherapeutic treatment, 5-FU, in Breast cancer (BC) progression in both cellular and animal models. Material and Methods: MTT, Real-Time PCR, Western Blotting, Hematoxylin and eosin (H&E) tissue staining were applied to determine the anti-tumor properties of crocin in in vitro and in vivo samples. Results:: Our findings showed that crocin decreased breast cancer cell proliferation by suppressing cyclin D1 expression and Wnt/β-catenin signaling activation. Moreover, this molecule improved 5- FU anti-cancer activities by decreasing the tumor volume and weight, increasing tumor necrosis, and suppressing tumor inflammation in an animal model. Inflammation-associated anti-cancer activity of crocin is mediated by the down-regulation of pro-inflammatory genes, including IFN-γ and IL-1β, as well as inhibition of oxidative stress responses within the tumor environment. Conclusion:: This is the first study demonstrating the potent anti-tumor properties of crocin against BC progression. Our results suggest that this effective and low-toxic molecule could be a promising agent for reducing BC tumor progression when administered either alone or in combination with standard treatment in breast cancer patients.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unifying Theory and Experiments: Multi-Target Pharmacology of Dajihan Pill Against Hyperlipidemia","authors":"Ning Li, Canfeng Bian, Ya Gao, Lingfei Liu, Qin Hu, Lixia Xiao, Tianzhu Guan","doi":"10.2174/0115701808277988240105083347","DOIUrl":"https://doi.org/10.2174/0115701808277988240105083347","url":null,"abstract":"Background: The increasing incidence of hyperlipidemia (HLP) is attributed to the imbalance in redox homeostasis, aberrant lipid metabolism, and the excessive intake of empty calories. Dajihan Pill (DJHP) is a Traditional Chinese Medicine (TCM) formula composed of Zingiberis Rhizoma (ZR), Piperis Longi Fructus (PLF), Alpiniae Officinarum Rhizome (AOR), and Cinnamomi Cortex (CC) in a ratio of 3:2:3:2. It exhibits a significant preventive effect on HLP. Certainly, the active components and the precise mechanism of action are not fully understood. Therefore, this study aims to elucidate the preventive and ameliorative mechanisms of DJHP against HLP by integrating network pharmacology, molecular docking, and experimental validation. Method: Based on the pharmacological method, active ingredients in DJHP and targets were extracted from Traditional Chinese Medicine System Pharmacology (TCMSP) and UniProt. Then core compounds and targets were obtained by constructing “compounds-targets-disease” and proteinprotein interaction (PPI) network. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to elucidate further the associated action mechanism. The molecular binding mechanisms between the core ingredients and targets were elucidated through molecular docking. Additionally, the antioxidant capacities of DJHP extracts were investigated by assessing their DPPH, hydroxyl, and ABTS radical scavenging activities. Results: A total of 45 active compounds and 258 targets were identified in DJHP. Network analysis indicated that quercetin, beta-sitosterol, kaempferol, and oleic acid might serve as core bioactive compounds. Seven core targets, including AKT1, INS, and TNF, were identified as potential preventive targets. GO analysis suggested the improvement of HLP by DJHP may be related to the lipid metabolic process, high-density lipoprotein particle, triglyceride binding, and inflammatory response. The KEGG analysis indicated TNF, HIF-1, and AMPK signaling pathways were involved. The observations of active compounds binding with core targets indicated an excellent combination. Additionally, antioxidant results showed that DJHP exhibited significant DPPH, hydroxyl, and ABTS radical scavenging activities. Conclusion: Theoretical and experimental investigations indicate that DJHP can effectively modulate various signaling pathways and enhance the redox system, thus mitigating HLP. Our work provided a basis for the pharmacological study of DJHP in preventing HLP and further research.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139515491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Some Novel 4-bromobenzoic Acid Clubbed Hydrazone Schiff Base Derivatives as Potent α-amylase Inhibitors: In vitro and In silico Studies","authors":"Momin Khan, Faima Alam, Aftab Alam, Abdul Wadood, Sulaiman Shams, Mehboob Ali, Sana Shah, Abullah F. AlAsmari, Metab Alharbi, Fawaz Alasmari","doi":"10.2174/0115701808262821231114114237","DOIUrl":"https://doi.org/10.2174/0115701808262821231114114237","url":null,"abstract":"Aims:: Synthesis of novel 4-bromobenzoic acid-based hydrazone-Schiff base derivatives and to screen them for their α-amylase inhibitory activity. Objective:: The biological activities of hydrazone-Schiff base compounds encouraged us to evaluate the synthesized derivatives (4-32) for in-vitro inhibition activity against the α-amylase enzyme. Methods:: In current research work twenty-nine Schiff base derivatives (4-32) of 4-bromobenzoic acid were synthesized in worthy yields by treating various replaced aldehydes with 4- bromobenzohydrazide using methanol solvent in catalytic quantity of acetic acid. The products were structurally described through the support of several spectroscopic methods (EI-MS and 1HNMR) and finally evaluated against α-amylase enzyme. Results:: All the made derivatives exhibited worthy inhibition potential from IC50 = 0.21 ± 0.01 to 5.50 ± 0.01 μM when equated to the usual acarbose drug having IC50 = 1.34 ± 0.01 μM. Compound 21 (IC50 = 0.21 ± 0.01 μM) was established as the most active inhibitor among the series better than standard. The structure-activity relationship study showed that the alteration in the activity of the produced products might be due to the attached position and nature of the substituents. Furthermore, in-silico study supported the effects of groups attached on the binding interaction with α-amylase enzyme. Conclusion:: A series of substituted hydrazone Schiff bases based on 4-bromobenzoic acid were produced, confirmed the structures by EI-MS and 1H-NMR spectroscopic methods and lastly tested for their in-vitro α-amylase inhibitory potential. Among the series, twenty-four products indicated brilliant inhibition potential having IC50 values from 0.21 ± 0.01 to 1.30 ± 0.01 μM. The structure-activity relationship study showed that the alteration in the activity of the synthesized products might be due to the attached position and nature of the substituents. On the other hand, in silico studies advocated that the synthesized Schiff base derivatives have prevalent interactions of binding within the active site of the α-amylase enzyme, and because of their various attached substituent, their conformation is altered in the active site of the enzyme. The current study recognized a number of lead candidates derived from 4-bromobenzoic acid. Additional investigation of the synthesized derivatives for coming research to get novel α-amylase inhibitors.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139462140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D and 2D-QSAR Studies on Natural Flavonoids for Nitric Oxide Production Inhibitory Activity","authors":"Chunqiang Wang, Yuzhu Fan, Minfan Pei, Chaoqun Yan, Taigang Liang","doi":"10.2174/0115701808179188231205064327","DOIUrl":"https://doi.org/10.2174/0115701808179188231205064327","url":null,"abstract":"Background: Nitric oxide (NO), an important second messenger molecule, regulates numerous physiological responses, while excessive NO generates negative effects on the circulatory, nervous and immune systems. Recently, some natural flavonoids were reported to possess the capability of inhibiting LPS-induced NO production. To fully understand the nature of their own NO inhibitory activity, it is necessary to address the structural requirements of flavonoids as NO inhibitors. Objective: The objective of this work was to develop efficient QSAR models for predicting the NOinhibitory activity of new flavonoids and improving insights into the critical properties of the chemical structures that were required for the ideal NO production inhibitory activities. Methods: To provide insights into the structural basis of flavonoids as NO inhibitors, 3D quantitative structure-activity relationship (3D-QSAR) and 2D-QSAR models were developed on a dataset of 55 flavonoids using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and hologram quantitative structure-activity relationship (HQSAR) approaches. method: CoMFA, CoMSIA combining HQSAR methods were employed on a series of flavonoids to generate 3D and 2D-QSAR models. Results: The statistically significant models for CoMFA, CoMSIA and HQSAR resulted in crossvalidated coefficient (q2) values of 0.523, 0.572 and 0.639, non-cross-validated coefficient (r2) values of 0.793, 0.828 and 0.852, respectively. The robustness of these models was further affirmed using a test set of 18 compounds, which resulted in predictive correlation coefficients (r2 pred) of 0.968, 0.954 and 0.906. Furthermore, the models-derived contour maps were appraised for activity trends for the molecules analyzed. result: Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Indices Analysis (CoMSIA) combining hologram quantitative structure-activity relationship (HQSAR) methods were employed on a series of flavonoids to generate 3D and 2D-QSAR models. Result: The obtained models can be used to predict the activities of new flavonoids and identify the key structural features affecting the NO inhibitory activities. Conclusion: The 3D and 2D-QSAR models constructed in this paper were efficient in estimating the NO inhibitory activities of flavonoids and facilitating the design of flavonoid-derived NO production inhibitors. other: none","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139462171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of the Aminated Quinoxalines as Potential Active Molecules","authors":"Sedef Bener, Nilüfer Bayrak, Emel Mataracı-Kara, Mahmut Yıldız, Belgin Sever, Halilibrahim Çiftçi, Amaç Fatih Tuyun","doi":"10.2174/0115701808281517231215113741","DOIUrl":"https://doi.org/10.2174/0115701808281517231215113741","url":null,"abstract":"Background: In recent years, as the biological activity of the quinoxaline skeleton has been revealed in numerous studies, interest in synthesizing new prototype molecules for the treatment of many chronic diseases, especially cancer, has increased. Methods: The desired alkoxy substituted aminoquinoxalines (AQNX1-9) were synthesized by the reaction of QNX and alkoxy substituted aryl amines such as 2-methoxyaniline, 4-methoxyaniline, 2- ethoxyaniline, 3-ethoxyaniline, 4-ethoxyaniline, 4-butoxyaniline, 2,4-dimethoxyaniline, 3,4- dimethoxyaniline, and 3,5-dimethoxyaniline according to the previously published procedure. QNX was aminated in DMSO at 130°C. We synthesized various alkoxy-substituted aminoquinoxaline compounds (AQNX1-9) and evaluated their anticancer and antimicrobial activities in order to expand the search to related structures. In particular, two aminoquinoxaline (AQNX5 and AQNX6) compounds, coded as NSC D-835971/1 and NSC D-835972/1 by the National Cancer Institute in the USA, were screened for anticancer screening at a dose of 10-5 M on a full panel of 60 human cell lines obtained from nine human cancer cell types (leukemia, melanoma, non-small cell lung, colon, central (nervous system, ovarian, kidney, prostate, and breast cancer). objective: Therefore, we synthesized various alkoxy-substituted aminoquinoxaline compounds (AQNX1-9) and evaluated their anticancer and antimicrobial activities in order to expand the search to related structures. Results: Further in silico studies were also conducted for the compound AQNX5 (NSC D- 835971/1), which was found to be the most active antiproliferative agent, especially against leukemia cell lines. Molecular docking studies showed that AQNX5 interacted with Glu286 and Lys271 through hydrogen bonding and π-stacking interaction in the ATP binding region of Abl kinase, which is indicated as a potential target of leukemia. Besides, AQNX5 occupied the minor groove of the double helix of DNA via π-stacking interaction with DG-6. method: Especially, the two aminoquinoxalines (AQNX5 and AQNX6) with the NCI codes NSC D-835971/1 and NSC D-835972/1 selected by NCI, USA, were screened for anticancer screening at a 10-5 M dose in the full panel of 60 human cell lines derived from nine human cancer cell types (leukemia, melanoma, non-small-cell lung, colon, central nervous system, ovarian, renal, prostate, and breast cancer) at the NIH, Bethesda, Maryland, USA. Conclusion: According to in silico pharmacokinetic determination, AQNX5 was endowed with drug-like properties as a potential anticancer drug candidate for future experiments. In the light of these findings, more research will focus on aminated quinoxalines' ability to precisely target leukemia cancer cell lines. conclusion: In the light of these findings, more research will focus on aminated quinoxalines' ability to precisely target leukemia cancer cell lines.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139461968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel CDK 4/6 Inhibitors by High-throughput Virtual Screening","authors":"Abhijit Debnath, Rupa Mazumder","doi":"10.2174/0115701808273043231130100833","DOIUrl":"https://doi.org/10.2174/0115701808273043231130100833","url":null,"abstract":"Background:: CDK4/6 plays a crucial role in regulating cell proliferation, and inhibiting this kinase can effectively prevent the initiation of cell growth and division. However, current FDAapproved CDK4/6 inhibitors have limitations such as poor bioavailability, adverse effects, high cost, and limited accessibility. Thus, this research aimed to discover novel CDK4/6 inhibitors to overcome the challenges associated with FDA-approved inhibitors. Methods:: To identify potential CDK4/6 inhibitors, we have performed structure-based virtual screening. Chem-space and Mcule databases have been screened, followed by a series of filtering steps. These steps included assessing drug-likeness, PAINS alert, synthetic accessibility scores, ADMET properties, consensus molecular docking, and performing molecular dynamics simulations. Results:: Four new compounds (CSC089414133, CSC091186116, CSC096023304, CSC101755872) have been identified as potential CDK4/6 inhibitors. These compounds exhibited strong binding affinity with CDK4/6, possessed drug-like features, showed no PAINS alert, had a low synthetic accessibility score, demonstrated effective ADMET properties, were non-toxic, and exhibited high stability. Conclusion:: Inhibiting CDK4/6 with the identified compounds may lead to reduced cell proliferation and the promotion of cancer cell death. result: Four compounds (CSC089414133, CSC091186116, CSC096023304, CSC101755872) were identified as potential CDK4/6 inhibitors. These compounds exhibited strong binding affinity at the active site of CDK4/6, possessed drug-like features, showed no PAINS alert, had a low synthetic accessibility score, demonstrated effective ADMET properties, were non-toxic, and exhibited high stability.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139411912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico Investigation of the Pro-apoptotic Potential of Syringic Acid Analog","authors":"Hossein Hosseini, Reza Rajaie Khorasani, Sepideh Ketabi, Farrokh Roya Nikmaram","doi":"10.2174/0115701808275830231221192129","DOIUrl":"https://doi.org/10.2174/0115701808275830231221192129","url":null,"abstract":"Background: Conformational changes in BAX are associated with the activation of its pro-apoptotic potential. Previously, small molecule BAX antagonists have been shown to bring about apoptosis by inducing conformational changes in BAX by direct binding to the serine 184 site of BAX. Methods: In this article, we have proposed that syringic acid analog SA14 can incur apoptosis by directly binding to and inducing conformational changes in BAX. The pro-apoptotic potential of SA14 has been investigated using an in silico structure-based approach, i.e., docking and molecular dynamics computations are employed to study the binding of SA14 to the residues of the active site of BAX. Results: Based on docking results, four BAX-SA14 complexes, each representative of a cluster of conformations, have been selected for molecular dynamics simulations. The root mean square deviation has indicated the formation of stable conformations for two of the complexes. Other parameters, such as root mean square fluctuation, radius of gyration, and solvent accessible surface area, have been used to confirm the results, which have indicated favorable binding between BAX and SA14. Conclusion: Overall, the results have indicated that SA14 can bring about stable conformational changes in BAX and shows merit as a potential BAX-activating pro-apoptotic agent worthy of further experimental studies.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139412204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Mechanisms of Astragalus Membranaceus in Treating Pre-eclampsia Using Network Pharmacology and Molecular Docking","authors":"Jing Zhong, Liubing Lan","doi":"10.2174/0115701808267120231122070418","DOIUrl":"https://doi.org/10.2174/0115701808267120231122070418","url":null,"abstract":"Background: Pre-eclampsia (PE) is a pregnancy-related complication that has a global prevalence of 3-5% among pregnant women. Objective: The objective of this study is to examine the molecular mechanism underlying the therapeutic effects of Astragalus membranaceus (AE) in the treatment of PE through the application of network pharmacology and molecular docking. Methods: The databases, including TCMSP, Uniprot, Genecards, STRING, and DAVID, and software, including jvenn, Cytoscape, and AutoDock Vina, were used to do the analysis. Results: Sixteen AE-related active ingredients were screened, involving 127 targets, among which the main active ingredients included kaempferol, quercetin, and jaranol, etc. The primary targets of AE for the management of PE encompassed AKT1, CASP3, EGFR, IL1B, IL6, MMP9, PTGS2, TNF, TP53, and VEGFA. The outcomes of the enrichment analysis revealed that AE was predominantly implicated in pathways such as the IL-17 signaling pathway and PI3K-Akt signaling pathway, among others. The molecular docking findings confirmed that the principal active constituents exhibit favorable binding to their central targets. Specifically, the molecular docking results evinced that the primary active ingredients evince robust binding activity towards the core targets. Conclusion: AE has the potential to act synergistically in the management of PE by engaging multiple components, targets, and pathways, thereby establishing a basis for further exploration of its material basis and mechanism of action.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139373163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}