Drug Target Insights最新文献

{"title":"Optimizing ChEMBL-derived QSAR models for natural flavonoid screening: chemotype-specific predictive reliability in α-glucosidase-inhibition.","authors":"Radhiah Zakaria, Muhammad Iqhrammullah, Bryan Gervais de Liyis, Anggi Susilawati, Nizam Albar, Andriy Anta Kacaribu, Muhammad Habiburrahman","doi":"10.33393/dti.2026.3763","DOIUrl":"10.33393/dti.2026.3763","url":null,"abstract":"<p><strong>Introduction: </strong>α-Glucosidase inhibitors (AGIs) are essential for controlling postprandial hyperglycemia, with flavonoids representing a major class of natural AGIs. However, conventional quantitative structure-activity relationship (QSAR) models trained on structurally diverse datasets often exhibit limited predictive reliability for natural flavonoids due to chemical space mismatch. This study aimed to develop and optimize Random Forest-based QSAR models derived from ChEMBL AGIs and to evaluate their chemotype-specific applicability to natural flavonoids.</p><p><strong>Methods: </strong>ChEMBL-derived inhibitors were curated into two datasets: (i) a general scaffold-diverse dataset and (ii) a flavonoid-specific dataset. A custom RDKit-based pipeline employing SMARTS pattern recognition and fingerprint similarity automatically classified flavonoid chemotypes while excluding nonphenolic compounds. Molecular descriptors were calculated using Mordred. Regression and classification models were constructed with 10-fold cross-validation. External validation was performed using 15 literature-reported natural flavonoids categorized into flavones/flavonols (aglycones), flavonol glycosides, isoflavones, and flavan-3-ols.</p><p><strong>Results: </strong>The general model (n = 563) demonstrated strong regression performance (R² = 0.837) and classification accuracy (0.915). The flavonoid-specific model showed moderate regression (R² = 0.564) and classification accuracy (0.880). However, external validation revealed superior predictive reliability of the flavonoid-specific model, particularly for catechins (MAE = 0.182) and aglycones (MAE = 0.233). Predictive performance decreased for glycosides and isoflavones.</p><p><strong>Conclusion: </strong>Chemotype-focused QSAR modeling enhances predictive reliability for natural flavonoids. The optimized flavonoid-specific model is suitable for predicting pIC₅₀ of flavones and flavonols but should be applied cautiously to glycosylated or structurally divergent subclasses.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"46-54"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum in: <i>In vitro</i> and molecular docking evaluation of apigenin-7-<i>O</i>-glucuronide from <i>Psorospermum febrifugum</i> as anti-inflammatory and predicted antiplasmodial compound.","authors":"Fadimatou Abdourahman, Jean Noël Nyemb, Olga Nana, Boukli Hacene Faiza, Ghalem Meriem, Jean Momeni, Djeguedmbaye Bienvenu, Ghalem Said","doi":"10.33393/dti.2026.4770","DOIUrl":"https://doi.org/10.33393/dti.2026.4770","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.33393/dti.2026.3758.].</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"45"},"PeriodicalIF":3.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Withania somnifera</i> root extract reduces susceptibility of the model worm <i>Caenorhabditis elegans</i> to different types of stressors.","authors":"Nidhi Thakkar, Dilip Mehta, Vijay Kothari","doi":"10.33393/dti.2026.3737","DOIUrl":"10.33393/dti.2026.3737","url":null,"abstract":"<p><strong>Introduction: </strong><i>Withania somnifera</i>, commonly known as <i>Ashwagandha</i>, is one of the most widely prescribed plants in the Indian system of traditional medicine. Its roots are believed to impart comprehensive health benefits supporting lifespan and healthspan through their anti-stress, immunomodulatory, and neuroprotective activity. Scientific validation of its claimed biological effects is warranted.</p><p><strong>Methods: </strong>The nematode worm <i>Caenorhabditis elegans</i> was challenged with heat or certain neurotoxic/mitotoxic chemical stressors, and worm activity (healthspan) was compared between <i>W. somnifera</i> root extract (WSRE)-exposed and control worm populations through an automated worm tracker.</p><p><strong>Results: </strong>Previous exposure of worms to WSRE conferred prophylactic benefit on them in the face of subsequent challenge with rotenone, MnCl₂, or levamisole. Worms pre-exposed to either of these toxins were able to recover faster in the presence of WSRE. This extract was also able to reduce the susceptibility of wild-type worms to heat-induced paralysis and that of transgenic worms to beta-amyloid-mediated paralysis.</p><p><strong>Conclusions: </strong><i>W. somnifera</i> root extract improved the ability of <i>C. elegans</i> to withstand and recover from multiple stressors, consistent with its adaptogenic-like effects mentioned in traditional medicine. WSRE conferred protection on this worm against multiple stressors acting through different toxicological mechanisms. Our results support the candidature of <i>W. somnifera</i> roots as a potent nutraceutical. However, the underlying molecular targets and pathways remain to be elucidated.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"22-32"},"PeriodicalIF":3.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effects of Helmar-1 and Helmar-2 polyphenol extracts on mitochondrial bioenergetics, antioxidant defense, and lipid peroxidation in CCl₄-induced toxic hepatitis in rats.","authors":"Saidahon Ahmedova, Muzaffar Asrarov, Sobitjon Mirzakulov, Aliaksei Sysa, Anna Bokova, Sirojiddin Sultanov, Navruzov Gadoyniyoz","doi":"10.33393/dti.2026.3805","DOIUrl":"10.33393/dti.2026.3805","url":null,"abstract":"<p><strong>Introduction: </strong>Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis.</p><p><strong>Methods: </strong>Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria.</p><p><strong>Results: </strong>Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups.</p><p><strong>Conclusion: </strong>Overall, these results confirm that <i>Helichrysum maracandicum</i> polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"12-21"},"PeriodicalIF":3.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking and dynamics analysis of selected phytocompounds against multi-targeted hepatocellular carcinoma.","authors":"Narendran Chiterasu, Swarnalatha Yanamandala, Senthilkumar Chinnaiyan, Sivakumar Shanthirappan, Sidhika Kannan, Paul X Clinton, Karthick Vadivel, Kiruthika Alepalli Rangan, Suresh Babu Yashwanth","doi":"10.33393/dti.2026.3739","DOIUrl":"10.33393/dti.2026.3739","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide, with a five-year survival rate of only 19%. Although Sorafenib is the primary systemic therapy, its limited efficacy and complex interactions with signaling pathways highlight the need for multi-target drugs.</p><p><strong>Methods: </strong>This study evaluates the anti-cancer properties of selected phytochemicals against six key HCC target proteins, utilizing sorafenib tosylate as a positive control. Molecular docking was performed to evaluate binding affinities and interactions, and ADME/T predictions were generated to estimate drug-like properties. The top-ranking candidates were further evaluated using 100-ns molecular dynamics simulations to analyze conformational stability, protein-ligand interactions, and residue mobility.</p><p><strong>Results: </strong>Silymarin (SA) emerged as the most effective compound, demonstrating greater predicted inhibitory activity than Sorafenib. SA showed high binding affinity for target proteins 6HH1 (-9.9 kcal/mol) and 1CM8 (-9.6 kcal/mol). Molecular dynamics simulations also revealed increased stability of the SA-protein complexes, particularly for the 1CM8-SA complex, which maintained high conformational stability. The root-mean-square deviation (RMSD) value was found to be around 2.1 Å, and the root-mean-square fluctuation (RMSF) values were below 3 Å, indicating lower protein flexibility compared to both the native and sorafenib-bound complexes.</p><p><strong>Conclusion: </strong>These computational findings provide a strong theoretical basis for Silymarin's efficacy as a highly potent, multi-targeted therapeutic agent against HCC. The improved stability and binding properties of Silymarin compared with Sorafenib provide a strong rationale for advancing this compound into preclinical and clinical studies.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"3-11"},"PeriodicalIF":3.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative model organisms: growing popularity, and the challenges.","authors":"Vijay Kothari","doi":"10.33393/dti.2026.3733","DOIUrl":"10.33393/dti.2026.3733","url":null,"abstract":"","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"1-2"},"PeriodicalIF":3.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant potential of a new macrocyclic bisbibenzyl and other compounds from <i>Combretum molle</i>: <i>in vitro</i> and docking analyses.","authors":"Angele Fanta, Gaetan Bayiha Ba Njock, Amadou Dawe, Fawai Yakai, Jean Noël Nyemb, Herve Landry Ketsemen, Vincent Taira, Albert Wangso, Chantal Doudja, Dieudonne Emmanuel Pegnyemb, Benoit Loura","doi":"10.33393/dti.2025.3631","DOIUrl":"10.33393/dti.2025.3631","url":null,"abstract":"<p><strong>Introduction: </strong>Free radicals are key contributors to several diseases, including cancer, inflammation, pain, and neurodegenerative disorders such as Alzheimer's disease. Due to the limitations and adverse effects of synthetic antioxidants, naturally occurring phytochemicals offer safer, more sustainable alternatives. This study investigates the antioxidant potential of twigs of <i>Combretum molle</i> R. Br. ex G. Don through integrated experimental and computational approaches.</p><p><strong>Methods: </strong>Compounds were isolated using chromatographic methods, and their structures established by 1D- and 2D-NMR, HR-ESI-MS, and comparison with reported data. Antioxidant activity was assessed through DPPH radical scavenging and FRAP assays, while molecular docking against xanthine oxidase (PDB: 1FIQ) explored possible mechanisms beyond direct radical scavenging.</p><p><strong>Results: </strong>A new macrocyclic bisbibenzyl derivative, combrebisbibenzyl A (<b>1</b>), was identified along with corosolic acid (<b>2</b>), maslinic acid (<b>3</b>), a mixture of asiatic acid (<b>4</b>) and arjunolic acid (<b>5</b>), combregenin (<b>6</b>), and β-sitosterol glucoside (<b>7</b>). The MeOH extract and EtOAc fraction showed notable DPPH scavenging activity (IC₅₀ = 170.21 and 197.41 μg/mL) and strong reducing power (65.04 ± 1.07 and 67.42 ± 0.82 mM Vit C/g). Among the isolated compounds, combrebisbibenzyl A (<b>1</b>) displayed the strongest radical scavenging effect (IC₅₀ = 175.64 μg/mL) and high reducing capacity (57.46 ± 0.42 mM Vit C/g). Docking indicated favorable interactions for all compounds, with combrebisbibenzyl A (<b>1</b>) showing the highest affinity (-9.1 kcal/mol), outperforming salicylate (-7.7 kcal/mol).</p><p><strong>Conclusion: </strong>These findings support the traditional use of <i>C. molle</i> and highlight combrebisbibenzyl A (<b>1</b>) as a promising natural antioxidant with multi-mechanistic potential.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"108-115"},"PeriodicalIF":2.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ravulizumab in treatment-naïve patients with atypical hemolytic uremic syndrome: a real-world case series.","authors":"Sorrentino Livia Maria, Candida Iacuzzo, Raffaela Sciri, Miriam Zacchia, Mariarosaria Iannuzzi, Paola Marotta, Piercarla Vitale, Chiara Taglioni, Floriana Secondulfo, Daniela Palazzetti, Rocco Baccaro","doi":"10.33393/dti.2025.3616","DOIUrl":"10.33393/dti.2025.3616","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical hemolytic uremic syndrome (aHUS) is a potentially life-threatening condition associated with poor clinical outcomes if not treated adequately. Eculizumab has become the standard of care, whereas ravulizumab, a second-generation, high-affinity complement C5 inhibitor, demonstrates comparable efficacy in improving renal function, hematological markers, and dialysis rates. In addition, ravulizumab offers practical advantages, including a longer dosing interval and immediate, complete, and sustained inhibition of free C5, making it a valuable therapeutic option.</p><p><strong>Methods: </strong>Given the limited real-world experience with ravulizumab, we present a case series of six treatment-naïve aHUS patients who received ravulizumab as first-line therapy.</p><p><strong>Results: </strong>These cases include one pregnancy-related aHUS, one postpartum case, one related to a urinary tract infection, one associated with hypertension, one with a pneumonia-related trigger, and one kidney transplant patient with a prior verotoxin-producing <i>E. coli</i> infection. Altogether, these cases illustrate the challenges in diagnosing aHUS. The choice to administer ravulizumab as first-line treatment was sometimes made in the presence of a clear clinical suspicion, even when not all minor criteria seemed to confirm the diagnosis. In most patients, renal function improved rapidly after ravulizumab administration, followed by recovery of hematological parameters, which were stable in the longer term. As improvements remained sustained over time, the possibility of discontinuing ravulizumab can be evaluated on a case-by-case basis.</p><p><strong>Conclusion: </strong>These cases highlight the importance of early diagnosis, prompt intervention, and multidisciplinary care in managing aHUS. Ravulizumab as first-line therapy proved effective and well-tolerated, with sustained clinical improvements observed across diverse real-world scenarios.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"99-107"},"PeriodicalIF":2.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-occurrence of genes encoding carbapenem resistance and aminoglycoside resistance in clinical isolates of Enterobacterales.","authors":"Shradha Smriti, Gaurav Verma, Sujit Pradhan, Nipa Singh, Subhra Snigdha Panda, Ipsa Mohapatra, Dipti Pattnaik, Rajesh Kumar Dash, Liza Das","doi":"10.33393/dti.2025.3592","DOIUrl":"10.33393/dti.2025.3592","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to detect the co-occurrence of carbapenem resistance genes along with aminoglycoside-modifying enzyme (AME) genes in clinical <i>Enterobacterales</i> isolates to understand the distribution of multiple resistance genes among clinical isolates.</p><p><strong>Methods: </strong>This prospective study was conducted for six months (November 2024 to April 2025) in the department of microbiology of a tertiary care hospital. A total of 30 blood culture isolates were identified as resistant to both carbapenem and aminoglycoside antibiotics using the automated VITEK 2 compact system. The genes responsible for carbapenem resistance (<i>bla_NDM</i> , <i>bla_OXA-48</i> , <i>bla_KPC</i> , <i>bla_IMP</i> , and <i>bla_VIM</i> ) were detected by multiplex real-time PCR, and the aminoglycoside-modifying enzyme genes [APH(3')-Ia, APH(2\")-Ib, AAC(3)-IIc, AAC(6')-Ib, and ANT(3\")-I] were detected by the conventional polymerase chain reaction method. All the clinical data, patient demographics, and molecular findings were entered in an MS Excel spreadsheet version 14.0.4734.1000 and analyzed using GraphPad/PRISM software version 10.5.0.</p><p><strong>Results: </strong>Of the 30 <i>Enterobacterales</i> isolates, <i>Klebsiella pneumoniae</i> was the most common isolate (66.7%). Molecular detection revealed <i>bla_NDM</i> in 40% isolates and <i>bla_OXA48</i> in 10% isolates. The majority of the AME genes were in combination. The most common combination of the AME gene was AAC(6')-Ib+ AAC(3)-IIc+ ANT(3\")-I + APH(3')-I detected in 4 (13.3%) isolates. The most common combination of carbapenem and aminoglycoside resistant genes was <i>bla_NDM</i> + <i>bla_OXA48</i> + AAC(6')-Ib+ AAC(3)-IIc+ ANT(3\")-I+ APH(3')-I (13.3%). The <i>bla_OXA-48</i> gene had a statistically significant association with AAC(6')-Ib, ANT(3\")-I, and APH(3')-I (p <0.05).</p><p><strong>Conclusion: </strong>The Co-occurence of carbapenem resistance and aminoglycoside-modifying enzyme genes in clinical <i>Enterobacterales</i> isolates limits the therapeutic option.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"91-98"},"PeriodicalIF":2.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated <i>in vitro</i>, microarray, and network pharmacology analysis reveals the multi-target anti-diabetic potential of <i>Vigna unguiculata</i>.","authors":"Haseeba Sardar, Fatima Noor, Syed Muhammad Mukarram Shah, Ashraf Ullah Khan, Jamelah S Al-Otaibi, Fazal Hadi, Maria Daglia, Haroon Khan","doi":"10.33393/dti.2025.3495","DOIUrl":"10.33393/dti.2025.3495","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM), particularly type 2 DM (T2DM), is a chronic metabolic disorder requiring novel therapeutic approaches as the available therapies are not meeting the current challenges. This study investigates the anti-diabetic potential of Vigna unguiculata using a network pharmacology approach, supported by <i>in vitro</i> and <i>in silico</i> analyses.</p><p><strong>Methods: </strong>The plant was collected from Khyber Pakhtunkhwa, Pakistan, and subjected to hydroalcoholic extraction and fractionation. <i>In vitro</i> assays included α-amylase, α-glucosidase, and aldose reductase. Target prediction using STITCH and SwissTargetPrediction identified 88 common genes linked to T2DM. Protein-protein interaction (PPI) network analysis highlighted key genes like EGFR, PTGS2, and TLR4 as central nodes in diabetes-related pathways. Molecular docking was used to study the binding affinities of compounds.</p><p><strong>Results: </strong>IC50 values were determined using IBM SPSS Statistics 21 software. The data underwent analysis using one-way ANOVA followed by Dunnett's multiple comparison test. Significance value was determined at *p   0.05, **p   0.01 and ***p   0.001. In-vitro assays demonstrated significant α-amylase, α-glucosidase, and aldose reductase inhibitory activities. Phytochemical screening identified several bioactive compounds. Functional annotation and KEGG pathway analysis confirmed these genes' roles in crucial metabolic pathways. Virtual screening revealed strong binding affinities of compounds like Stigmasterol, Luteoline, and Quercetin with GSK3B, PTGS2, and TLR4. The Molecular Dynamics (MD) simulation, binding free energy calculations (MM-PBSA and MM-GBSA), confirmed the results of Virtual screening.</p><p><strong>Conclusion: </strong>In short, these findings underscore <i>V. unguiculata</i> as a promising source for anti-diabetic agents, supporting further clinical trials for T2DM management.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"71-90"},"PeriodicalIF":2.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}