Drug metabolism and personalized therapy最新文献

{"title":"<i>In vivo</i> and <i>in vitro</i> evaluation of antibacterial and anti-inflammatory activities of extraction of crude saponin isolated from licorice roots against <i>Streptococcus</i> <i>pneumoniae</i>.","authors":"Zinah Essam Hameed, Saja Majeed Shareef, Omar Hussein Ahmed","doi":"10.1515/dmpt-2025-0042","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0042","url":null,"abstract":"<p><strong>Objectives: </strong>Antibiotic resistance is a global health concern, prompting exploration of alternative therapies, including medicinal herbs. <i>Glycyrrhiza glabra</i> (licorice) contains saponins, which may possess antibacterial and antioxidant properties. This study aims to evaluate the antibacterial and antioxidant activities of saponin extracted from <i>G. glabra</i> and assess its safety and immunomodulatory effects <i>in vivo</i>.</p><p><strong>Methods: </strong>Saponin was isolated from licorice roots using a Soxhlet apparatus with 70 % ethanol as the extraction solvent over 168 h. Antioxidant activity of the extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging assay and ferric reducing antioxidant power (FRAP) assay. Antibacterial activity toward <i>Streptococcus pneumoniae</i> was detected using broth microdilution method to evaluate minimum inhibitory concentration (MIC). <i>In vivo</i> safety and immunomodulatory effects were assessed in mice.</p><p><strong>Results: </strong>Saponin exhibited an IC₅₀ of 20.16 ± 0.21 μg/mL in the DPPH assay. Inhibition zones against <i>S. pneumoniae</i> were observed at concentrations of 10 μg/mL (6.4 mm), 20 μg/mL (17.6 mm), and 50 μg/mL (21.9 mm). <i>In vivo</i>, treatment with 20 μg/mL saponin resulted in a 0.06 μg/mL fold increase in IFN-γ levels compared to control without adverse effects on hepatic enzymes, hematological parameters, or histopathology.</p><p><strong>Conclusions: </strong>Saponin from <i>G. glabra</i> demonstrates promising <i>in vitro</i> antioxidant and antibacterial activities against <i>S. pneumoniae</i>, with favorable safety and immunomodulatory profiles <i>in vivo</i>, supporting its potential as a natural therapeutic candidate.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174239","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":"Pharmaco-informatics screening of <i>Zingiber officinale</i> biomolecules targeting FOXO6 for chronic kidney disease therapy.","authors":"Shanmugampillai Jeyarajaguru Kabilan, Selvaraj Kunjiappan, Parasuraman Pavadai, Murugesan Sankaranarayanan, Krishnan Sundar","doi":"10.1515/dmpt-2025-0011","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0011","url":null,"abstract":"<p><strong>Objective: </strong>Ginger, scientifically known as <i>Zingiber officinale</i>, is a plant root that has a variety of therapeutic applications, including the treatment of nausea, inflammation, digestive problems, and management of renal function in chronic kidney disease (CKD). CKD is a life-threatening condition that, if untreated, leads to organ damage and is acknowledged as a global health concern. The present study aims at predicting bioactive compounds from <i>Z. officinale</i> that were identified through gas chromatography-mass spectroscopy (GC-MS), with the potential against a selected target of CKD, and was investigated using a pharmaco-informatics approach.</p><p><strong>Methods: </strong>The compounds from GC-MS analysis were screened, and the structures of identified compounds were drawn through ACD/Chemsketch 2021.2.1. Based on graph theoretical network analysis, forkhead box protein (FOXO6) was chosen as a potential target for CKD. The Swiss model was used to predict the structure of FOXO6, and the active site details were obtained. Docking was performed against the active sites of FOXO6 using 22 compounds, along with the standard drug, dapagliflozin. Pharmacokinetic, physicochemical and toxicity parameters were predicted for the selected high binders and dapagliflozin. The stability and intermolecular interactions of high binders and dapagliflozin protein-ligand complexes were studied using molecular dynamics simulation.</p><p><strong>Results: </strong>The binding affinity ranges from -3.5 to -6.7 kcal × mol^-1. Abietic acid and dehydroabietic acid had a higher binding affinity with a score of -6.7 kcal × mol^-1, similar to the standard drug, dapagliflozin (-6.4 kcal × mol^-1). Both abietic acid and dehydroabietic acid also have good bioavailability scores. MD simulation studies indicated greater stability for abietic acid-FOXO6 and dehydroabietic acid-FOXO6 complexes.</p><p><strong>Conclusions: </strong>This investigation has shed light on the significance of the compounds of <i>Z. officinale</i> R. as potential FOXO6 inhibitors, which could further be used as a lead compound for developing alternative therapy for CKD.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552504","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":"Clinical pharmacogenomics guidelines: recommendations in different countries and health care systems.","authors":"Ingrid Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmpt-2025-0028","DOIUrl":"10.1515/dmpt-2025-0028","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"77-78"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207923","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":"Vanari Gutika supplementation enhances testicular function by modulating spermatogenesis, oxidative balance, and blood-testis barrier integrity.","authors":"Arti Rajpoot, Anupam Yadav, Shubhanshu Yadav, Raghav Kumar Mishra","doi":"10.1515/dmpt-2024-0102","DOIUrl":"https://doi.org/10.1515/dmpt-2024-0102","url":null,"abstract":"<p><strong>Objectives: </strong>Vanari Gutika (VG) is an ayurvedic formulation that has been traditionally utilized for the treatment of various male sexual problems. The primary components of VG include <i>Mucuna pruriens</i>, honey, and clarified butter, which are recognized for their aphrodisiac properties. However, currently, there is no scientific evidence supporting the use of this formulation as a drug for enhancing male fertility or elucidating its mechanism for improving testicular physiology. This study aimed to examine the effect of VG on spermatogenesis.</p><p><strong>Methods: </strong>Adult male mice received oral administration of VG at doses of 75, 150, and 300 mg/kg body weight daily for 35 days (one spermatogenic cycle). Parameters such as histomorphology of testes, daily sperm production, sperm parameters, activity of antioxidant enzymes (SOD and catalase), and immunoblotting of BTB marker proteins (N-cadherin, connexin 43, β-catenin) were assessed.</p><p><strong>Results: </strong>VG treatment markedly improves relative testis weight, DSP, and sperm count compared to control. The administration of VG resulted in significant improvements in testis histomorphology, germ cell proliferation, and anti-oxidant enzymes (increased catalase and SOD activities) when compared to control mice. Additionally, there was also a dose-dependent increase in the expression of BTB junctional proteins. VG treatment (150 and 300 mg/kg BW) showed a significant beneficial impact on spermatogenesis in adult male mice.</p><p><strong>Conclusions: </strong>Thus, our findings strongly support the potent therapeutic potential of Vanari Gutika as an ayurvedic aphrodisiac in enhancing testicular function.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181012","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":"Assessment of thiopurine S-methyltransferase allele frequencies and phenotype-genotype concordance in a Tunisian population.","authors":"Safa Souissi, Wissem Ben Azzouz, Mouna Ben Sassi, Syrine Ben Hammamia, Mouna Daldoul, Hanene El Jebari, Mohamed Zouari, Rim Charfi, Riadh Daghfous, Emna Gaies, Sameh Trabelsi","doi":"10.1515/dmpt-2025-0001","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0001","url":null,"abstract":"<p><strong>Objectives: </strong>Thiopurine S-methyltransferase (TPMT) polymorphisms are associated with low or absent enzyme activity and, consequently, increased myelosuppression risk after conventional doses of azathioprine. The distribution of frequencies for deficient <i>TPMT</i> genotypes differs between ethnic groups. Due to limited data in Tunisia, we aimed to detect <i>TPMT</i> variant alleles (<i>TPMT</i>*2, *3B, *3C, *4) in Tunisian patients on azathioprine, and to investigate the concordance between <i>TPMT</i> phenotyping and genotyping for common <i>TPMT</i> alleles.</p><p><strong>Methods: </strong>We conducted a total of 32 genotyping assays in patients treated with azathioprine, who were referred to the Clinical Pharmacology Department for therapeutic monitoring of azathioprine metabolites from 2021 to 2024. <i>TPMT</i> phenotyping was performed by measuring azathioprine metabolites (6-TGN and 6-MMP) in patients' red blood cells using HPLC method. <i>TPMT</i> genotyping was performed using next generation sequencing to detect the following nucleotide substitutions: c.238G>C, c.460G>A, c.719A>G and c.626-1G>A.</p><p><strong>Results: </strong>Twenty-eight patients (87.5 %) were homozygous for the wild type. Four individuals (12.5 %) were <i>TPMT</i> deficient subjects and all carriers for <i>TPMT</i> *3C allele. No individual was carrier of the <i>TPMT</i> *2 or *4 allele. The overall concordance between genotyping and phenotyping in this population was 68.8 %.</p><p><strong>Conclusions: </strong>Overall, 12.5 % of the Tunisian subjects were found to carry the <i>TPMT</i> *3C allele. However, <b>detecting novel and rare TPMT alleles within a larger cohort</b> essential for more accurate estimation of genotype-phenotype correlation in our population. Combining genotyping and phenotyping is likely represents the most effective approach to prevent life-threatening myelosuppression associated with thiopurines.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179938","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":"Lauric acid modulates cytochrome 4V2 expression in the human THP1 macrophages.","authors":"Yazun Bashir Jarrar, Wisam Nasser, Su-Jun Lee","doi":"10.1515/dmpt-2025-0008","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0008","url":null,"abstract":"<p><strong>Objectives: </strong>Macrophages play a major role in the inflammation. Recently, the expression of some cytochrome P450 (CYP450) 4 family enzymes was identified in the macrophages including CYP4V2, which metabolizes saturated fatty acids. Lauric acid is unsaturated fatty acid, which can induce inflammation. Its effect on the expression of CYP4V2 and the inflammatory mediators in macrophages is still unknown. This study aims to investigate the effect of lauric acid on the expression of CYP4V2 and cyclo-oxygenase 2 (COX2) in the human monocytes and macrophage THP1 cell line.</p><p><strong>Methods: </strong>The THP1 monocyte cell line was differentiated into macrophages using 100 ng/mL PMA. Then, the cells were treated with 10 µM lauric acid for 72 h. The mRNA and protein expression of human CYP4V2 and COX2 were analyzed using real-time and western blot techniques, respectively.</p><p><strong>Results: </strong>It was found that the mRNA and protein expression of CYP4V2 was upregulated after treatment of the macrophages with lauric acid in a dose-dependent manner. This upregulation was correlated with the expression of COX2.</p><p><strong>Conclusions: </strong>It can be concluded from the results of this study that mRNA and protein expression of CYP4V2 are upregulated by lauric acid in correlation with the induction of inflammation. CYP4V2 can play a role in the inflammation process managed by macrophages.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149656","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":"Immunomodulatory potential of phosphorus: insights from experimental mice models under normal and immunosuppressive condition.","authors":"Sangita Behera, Mahima Sharma, Raj Kumar Regar, Pankaj Gupta, Shaheen Jabbar, Godlaveti Vijay Narasimha Kumar, Satvinder Singh","doi":"10.1515/dmpt-2024-0103","DOIUrl":"10.1515/dmpt-2024-0103","url":null,"abstract":"<p><strong>Objectives: </strong>Phosphorus, an essential mineral with diverse biological functions, has recently garnered attention for its potential role in modulating the immune system. However, no study is present regarding the effect of homoepthic preparation of Phosphorus on immune system. Thus, this study aims to investigate the immunomodulatory effects of Phosphorus, shedding light on its impact on Normal and Immunosuppressive conditions in mice.</p><p><strong>Methods: </strong>The immunomodulatory effect of Phosphorus 6C, 30C, and 200C was tested using Sheep red blood cells on humoral antibody titer and delayed-type hypersensitivity assays. The effect of Phosphorus was investigated in cyclophosphamide induced immune-compromised mice by assessing hematology, organ index, phagocytic index, histology, cytokine level, and their mRNA expression in the spleen.</p><p><strong>Results: </strong>Phosphorus 6C produced a significant increase in the primary and secondary humoral immune response. While Phosphorus treatment at 6C, 30C, and 200C did not significantly alter hematological and organ index parameters, it considerably enhance the phagocytic index at 30C and 200C, and raise the levels of TNF-α and IL-2 in mice against immunosuppression induced by CPM after the pretreatment with Phosphorus-30C.</p><p><strong>Conclusions: </strong>The present study shows that Phosphorus 6C potency augment the humoral immunity. In case of immunosuppression, Phosphorus at high dilution might play a significant role but more research is needed to find out the possible effect of Phosphorus preparation.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"131-141"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982807","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":"Navigating the crossroads of cell death interplay and intersections among ferroptosis, apoptosis and autophagy.","authors":"Anuupama Suchiita, Navya Gupta, Kajal Nandi, Binita Goswami","doi":"10.1515/dmpt-2024-0073","DOIUrl":"10.1515/dmpt-2024-0073","url":null,"abstract":"<p><p>The review article, \"Navigating the Crossroads of Cell Death: Interplay and Intersections Among Ferroptosis, Apoptosis, and Autophagy,\" delves into the complex interactions between these three key cell death pathways. Understanding how ferroptosis, apoptosis, and autophagy intersect is crucial for maintaining cellular homeostasis. Each pathway represents a unique mechanism of cell death, and recent research highlights their intricate interconnections and mutual influences. Exploring these relationships is vital for comprehending how cells make fate decisions and how these processes are implicated in various diseases. The review's significance lies in elucidating the molecular details of cell death and providing insight into how cells balance survival and death. The interplay among ferroptosis, apoptosis, and autophagy has important implications for developing therapeutic interventions, particularly in diseases where cell death regulation is disrupted. By examining the molecular crosstalk between these pathways, researchers can identify new drug targets and devise strategies to modulate cell fate effectively. This review aims to enhance our understanding of cell biology by offering a detailed perspective on the dynamic and interconnected nature of these cell death mechanisms.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"89-105"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991420","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":"Systems pharmacology of phytochemical anacardic acid in the chemoprevention of hepatocellular carcinoma.","authors":"Sangita Panda, Enketeswara Subudhi, Sweta Padma Routray, Sujit Nair","doi":"10.1515/dmpt-2024-0099","DOIUrl":"10.1515/dmpt-2024-0099","url":null,"abstract":"<p><strong>Objectives: </strong>Hepatocellular carcinoma (HCC) is a common type of liver cancer that progresses quickly and has limited treatment options. Nutraceutical anacardic acid (AA), a bioactive compound derived from cashew nut shell, has emerged as a potential candidate for HCC treatment owing to its reported anti-inflammatory, anticancer and diverse pharmacological properties. In the present study, we investigate the potential of AA as an HCC inhibitor using molecular docking, gene ontology, and network pharmacology.</p><p><strong>Methods: </strong>The pharmacokinetic and physicochemical properties of AA were assessed using Swiss ADME. SuperPred, Similarity Ensemble Approach, ChEMBL and Swiss Target Prediction online tools were used for determining molecular targets of AA. In addition, GeneCards, NCBI, DisGeNET and UniProt ID were used to search the targets of HCC and the top 25 hub genes were determined using Cytohubba plugin. A protein protein interaction (PPI) network was constructed through the STRING database. Gene Ontology (GO) biological process and Kyoto Encyclopaedia of Genes and Genes (KEGG) pathway enrichment analysis were performed through FunRich and ShinyGO 0.77. Moreover, molecular docking studies were performed on NF-κB and GSK-3β. The expression levels of the hub genes were also validated by western blotting.</p><p><strong>Results: </strong>Comprehensive data analysis identified 375 targets for AA and 11,333 for HCC, with 264 targets in common. Network analysis determined 25 key HCC targets, including caspase-3, and NF-κB. Gene ontology and topology analysis highlighted essential pathways implicated in HCC progression such as the renin-angiotensin system, VEGF signalling, and apoptosis. Molecular docking analysis revealed strong binding affinity of HCC proteins with NF-κB and GSK-3β. Upregulation of p-NRF2 and p-GSK-3β, and downregulation of p-NF-κB and caspase-1 expression were validated using western blotting.</p><p><strong>Conclusions: </strong>Taken together, our study highlights the potential of AA as a promising chemopreventive agent for HCC because of its significant modulatory effects on important regulatory proteins linked to cell division, inflammation, apoptosis, and antioxidant response.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"107-120"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986903","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":"Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.","authors":"Pralhad Wangikar, Pradhnya Chaudhari, Eshita Sharma, Chhaya Godse, Ashit Vora, Sujit Nair","doi":"10.1515/dmpt-2024-0100","DOIUrl":"10.1515/dmpt-2024-0100","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"143"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976686","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}