Current drug metabolism最新文献

{"title":"Transcriptomic and Proteomics Analysis of a Lipid-Loaded HepaRG Model for Steatosis Reveals Altered Regulation in Lipid and Xenobiotic Metabolism.","authors":"Anitha Saravanakumar, Cassandra A Tierney, Wen He, Rohitash Jamwal, Benjamin Barlock, Xin Bush, Jillian G Johnson, David A Rodrigues, Fatemeh Akhlaghi","doi":"10.2174/0113892002381234250727004847","DOIUrl":"https://doi.org/10.2174/0113892002381234250727004847","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatic lipid accumulation (steatosis) is an early indicator of non-alcoholic fatty liver disease (NAFLD), preceding fibrosis and cirrhosis. Understanding its effects on drug-me-tabolizing enzymes (DMEs) and transporters is crucial for assessing potential alterations in drug dis-position among NAFLD patients. This study aimed to replicate steatosis in an in vitro HepaRG cell model and analyze its impact on DMEs and transporters.</p><p><strong>Methods: </strong>Differentiated HepaRG cells were treated with a mixture of saturated (palmitate) and unsatu-rated (oleate) fatty acids (in a 1:2 ratio at 0.5 mM), complexed with BSA for 72 hours to induce lipid accumulation. Confirmation of steatosis was performed using Oil Red O staining and triglyceride (TG) quantification, while cell viability was assessed via the WST-1 assay. RNA sequencing and SWATH-MS proteomic analysis were employed to identify differentially expressed transcripts and proteins in lipid-loaded cells compared to controls.</p><p><strong>Results: </strong>Lipid loading resulted in a ~6-fold increase in TG concentration without compromising cell viability. Transcriptomic analysis identified 393 differentially expressed transcripts (89 upregulated, 304 downregulated), while proteomic analysis detected 165 differentially expressed proteins (127 up-regulated, 38 downregulated). Notably, key mRNA transcripts related to transcription factors (NR1I2, HNF4α), phase 1 DMEs (CYP1A2, 2B6, 2C8, 2C9, 2C19, 3A4), phase 2 DMEs (UGT1A6, 2B7, SULT2A1, 1E1), and transporters (ABCC11, ABCG5, SLCO2B1, SLC10A1) exhibited significant downregulation.</p><p><strong>Discussion: </strong>The observed alterations in DMEs and transporters suggest a potential shift in drug me-tabolism pathways under NAFLD conditions. Downregulation of transcription factors and metabolic enzymes could impact drug efficacy and toxicity, necessitating further research into the pharmacoki-netic implications.</p><p><strong>Conclusion: </strong>The in vitro hepatic steatosis model demonstrated significant changes in the expression of clinically relevant DMEs and transporters. These findings highlight the importance of considering NAFLD-induced metabolic alterations when assessing drug disposition in affected patients.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063579","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":"Mechanism of Tetrandrine in Ameliorating Hypoxic Pulmonary Hypertension Vascular Remodeling through Transcriptomics and Metabolomics.","authors":"Xiaowei Gong, Feitian Min, Junli Guo, Ziping Zhang, Xin Liu, Wei Guo, Yaguang Wu, Hanzhou Li, Xixing Fang, Yadong Yuan, Yanling Sheng, Huantian Cui","doi":"10.2174/0113892002393801250812063417","DOIUrl":"https://doi.org/10.2174/0113892002393801250812063417","url":null,"abstract":"<p><strong>Background: </strong>Tetrandrine (TET) demonstrates therapeutic potential for hypoxic pulmonary hypertension (HPH); however, its precise pharmacological mechanisms remain unclear. In this study, we aimed to investigate the effects of TET on pulmonary vascular remodeling (PVR) in HPH and elucidate the molecular pathways through which TET ameliorates HPH.</p><p><strong>Methods: </strong>We established a rat model of HPH and evaluated the therapeutic effects of TET by measuring hemodynamic parameters, assessing right ventricular hypertrophy, and analyzing pathological changes in lung tissue. To explore the molecular mechanisms, we carried out comprehensive analyses using transcriptome and untargeted metabolomics technologies to examine the impact of TET on gene expression and metabolite profiles in the lung tissue of HPH rats. Using data from these multiomics analyses, we performed biochemical assays, immunofluorescence staining, and Western blotting to validate the effects of TET on vasoconstriction and angiogenesis-related factors. These experiments provide further evidence of the anti-HPH and anti-PVR properties of TET.</p><p><strong>Results: </strong>TET intervention significantly reduced hemodynamic parameters, including mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP), as well as right ventricular hypertrophy indices, such as the right ventricular hypertrophy index (RVHI) and right ventricle-to-body weight ratio (RV/BW), in HPH rats. TET inhibited smooth muscle cell proliferation and alleviated pathological changes in lung tissue. Transcriptome and metabolome analyses revealed that genes affected by TET intervention were enriched in pathways related to PVR, including those involved in endothelial and smooth muscle cell proliferation, angiogenesis, and blood vessel morphogenesis. Metabolites were predominantly associated with the arachidonic acid (AA) metabolism pathway. Differentially expressed genes included Cyp4a1, Cyp4a3, Cyp2u1, and Alox15. Validation experiments demonstrated that TET upregulated ALOX15 protein expression and downregulated CYP4A and CYP2U1 proteins, modulating levels of arachidonate metabolites 20-HETE and 15(S)-HPETE. We further observed that TET reduced the levels of PVR markers, including endothelin-1 (ET-1) secretion, while increasing nitric oxide (NO) release. TEt also decreased the expression of cell proliferation markers PCNA and Ki-67 and elevated the endothelial marker CD31. Moreover, TET intervention suppressed angiogenic and vasoconstrictive factors, such as MMP-9, TGF-β1, IGF2, and PDGF-B, while enhancing levels of FGF9 and NOS3.</p><p><strong>Conclusion: </strong>Our findings highlight the protective effects of TET on lung tissue in HPH mediated through the regulation of 15(S)-HPETE and 20-HETE within the arachidonic acid metabolism pathway. This regulation inhibits pulmonary angiogenesis and vasoconstriction, ultimately improving PVR in HPH.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014093","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":"Comparative Pharmacokinetics of Five Major Ingredients in Normal and Atherosclerotic Rats after Oral Administration of Shenlian Formula.","authors":"Yan Caiying, Wang Xinge, Qin Linying, Yang Qing, Chen Ying, Li Qi, Zhu Xiaoxin, Yang Lihong, Cheng Long, Dong Yu","doi":"10.2174/0113892002387343250807080059","DOIUrl":"https://doi.org/10.2174/0113892002387343250807080059","url":null,"abstract":"<p><strong>Introduction: </strong>Shenlian formula (SL) has been widely used to treat various diseases, including type 2 diabetes mellitus and atherosclerosis (AS). Pathological states can significantly alter drug pharmacokinetics (PK) compared to normal physiology, primarily by modulating biological membrane permeability and metabolic enzyme activity, thereby affecting drug absorption, distribution, metabolism, and excretion. However, the specific influence of AS on the PK profile of SL remains uncharacterized.</p><p><strong>Objective: </strong>To investigate the plasma PK of five components (Salvianolic acid A [SAA], Danshensu [DSS], Andrographolide [AND], Neoandrographolide [NAND], and Dehydrated andrographolide [DDAND],) which were the ingredients of SL, in physiological and AS rats administered SL intragastrically.</p><p><strong>Methods: </strong>The AS SD rat model was induced with a high-fat diet, carotid balloon injury, and VD3 injections. A validated LC-MS/MS method quantified plasma concentrations to assess PK parameters.</p><p><strong>Results: </strong>The validation parameters were all in accordance with the current standards. Comparative PK analysis revealed significant intergroup disparities between the AS and normal groups. The value of Cmax and AUC0-t for DSS was significantly decreased (P<0.05) in the AS group, which indicated that the absorptive amount in vivo was remarkably attenuated in the pathological state. Additionally, the variation trend of AND under Cmax and AUC0-t values were consistent with the alteration trend of DSS. Furthermore, the Tmax of NAND in the AS group was significantly reduced (P<0.05), confirming that the pathological state accelerated the absorption rate of NAND, thereby shortening the time required for NAND to reach its maximum concentration in the body.</p><p><strong>Conclusion: </strong>We established and validated a sensitive LC-MS/MS method for the simultaneous quantification of five bioactive components of SL in rat plasma. This method is applicable to both physiological and pathological states. Comparative pharmacokinetic analysis revealed significant differences in the systemic exposure of all five analytes between AS and normal rats. These findings provide critical PK evidence for optimizing SL dosage regimens in AS patients, underscoring the imperative to consider the disease' status when determining therapeutic strategies for traditional Chinese medicine formulations.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999863","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":"Biopharmaceutical Factors Involved in the Disposition of Mycophenolic Acid: A Comprehensive Review of ADME Properties and Their Potential Impact on Mycophenolic Acid Plasma Exposure.","authors":"Eric Asare, Ting Du, Huan Xie, Dong Liang, Song Gao","doi":"10.2174/0113892002377209250815023105","DOIUrl":"https://doi.org/10.2174/0113892002377209250815023105","url":null,"abstract":"<p><p>Mycophenolic acid (MPA) is an approved drug widely used as an immunosuppressant agent for the prevention of rejection in organ transplant patients and for managing various autoimmune disorders. Pharma-cological studies have shown that the plasma exposure of MPA is critical to to maintaining its efficacy, leading to a significant focus on MPA therapeutic drug monitoring (TDM) in clinical practice. Additionally, many papers have been published regarding MPA's absorption, distribution, metabolism, and elimination (ADME) characteristics, which are the key disposition factors affecting the plasma exposure of MPA. In this paper, we synthesize the current data and information in the literature on the ADME properties of MPA and discuss their implications for MPA's TDM. We also analyze the disposition of MPA major metabolites mycophenolic acid-glucuronide (MPAG), and acyl-glucuronide (AcMPAG), highlighting the key factors that affect MPA plasma exposure, including the influence of transporters, namely Multidrug Resistance-Associated Protein 2 (MRP2), Breast Cancer Resistance Protein (BCRP), Organic Anion-Transporting Polypeptides (OATPs), metabolic en-zymes (i.e., UDP-Glucuronosyltransferases (UGTs)), enterohepatic recycling (EHR), and protein binding. We expect to provide researchers with a comprehensive understanding of factors that could affect MPA's TDM to ensure its efficacy.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945971","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":"Advances in Controlled Release Formulations for Ocular Diseases: Improving Patient Compliance and Therapeutic Outcomes.","authors":"Smita Narwal, Dushyant, Gurvirender Singh, Nisha Grewal, Vishal Chanalia, Ashwani K Dhingra","doi":"10.2174/0113892002384586250731104453","DOIUrl":"https://doi.org/10.2174/0113892002384586250731104453","url":null,"abstract":"<p><p>A majority of the global population suffers from eye diseases, but few effective treatment options are available with ophthalmic drug therapies. The reasons that have been identified are (1) lack of awareness about the options for treatments, drugs, polymeric science, or physiological barriers, (2) limitations in bringing drug therapies to the posterior segment of the eye due to physiological or anatomical limitations, and (3) regulatory and production difficulties of ocular drug products. Innovative ocular medication delivery and therapies are covered in this study, including hydrogels, nano micelles, implants, nanoparticles, microparticles, liposomes, in situ gels, and microneedles. Moreover, due to their potential to capture both hydrophilic and lipophilic medications, increase ocular permeability, prolong the period of residence, enhance drug stability, and increase bioavailability, this review includes nanotechnology-based carriers. The research encompassed various eye disorders, obstacles to ocular delivery, multiple ocular administration routes, a range of nanostructured platforms, characterization approaches, methods to improve ocular delivery, and emerging technologies. This review aims to provide information on the anatomy of the eye, various ocular conditions, and obstacles to ocular delivery. The benefits and drawbacks of various ocular dose forms or delivery techniques are also evaluated. Finally, it describes methods for increasing ocular bioavailability.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945900","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":"Emerging Approaches in Data-Driven Drug Discovery for Rare Diseases.","authors":"Mohamed Abbas, Muneer Parayangat, Mohammad Alaa Hussain Al-Hamami, Hashim Elshafie, Mohamad Yahya H Al-Shamri, R Resmi","doi":"10.2174/0113892002383220250729100138","DOIUrl":"https://doi.org/10.2174/0113892002383220250729100138","url":null,"abstract":"<p><p>Rare diseases present unique challenges in drug discovery and development, primarily due to small patient populations, limited clinical data, and significant variability in disease mechanisms. The primary objective of this review is to examine the integration of pharmacokinetics (PK) and drug metabolism data into data-driven drug discovery approaches, particularly in the context of rare diseases. By incorporating advanced computational techniques such as Machine Learning (ML) and Artificial Intelligence (AI), researchers can better predict PK parameters, optimize drug candidates, and identify personalized therapeutic strategies. AI integration with genomic and proteomic data reveals previously unidentifiable pathways, fostering collaboration among researchers, clinicians, and pharmaceutical companies. This interdisciplinary approach reduces development timelines and costs while enhancing the precision and effectiveness of therapies for patients with rare diseases. This review highlights the critical role of absorption, distribution, metabolism, and excretion (ADME) in understanding drug behavior in genetically diverse populations, thereby enabling the development of tailored treatments for patients with rare diseases. Additionally, it evaluates the opportunities and limitations of integrating PK/PD (pharmacodynamics) models with multi-omics data to improve drug discovery efficiency. Key examples of enzyme-drug interactions, metabolic pathway analysis, and AIbased PK simulations are discussed to illustrate advancements in predictive accuracy and drug safety. This review concludes by emphasizing the transformative potential of integrating PK and metabolism studies into the broader framework of data-driven drug discovery, ultimately accelerating therapeutic innovation and addressing unmet medical needs in rare diseases.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945940","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":"Comprehensive Insights into Licochalcone A: its Distribution, Biosynthesis, Metabolism, and Pharmacological Effects.","authors":"Xiaoxiao Wang, Jinrui Liu, Wei Li, Xingjie Tao, Chenxi Yu, Junbo Xie, Yanqing Zhang","doi":"10.2174/0113892002380407250730080035","DOIUrl":"https://doi.org/10.2174/0113892002380407250730080035","url":null,"abstract":"<p><p>Licochalcone A (LCA) is an important secondary metabolite in licorice that has attracted extensive attention due to its unique species-specific distribution characteristics and various pharmacodynamic activities, particularly its anti-inflammatory and anti-cancer effects. LCA was originally considered exclusive to Glycyrrhiza inflata Batal. However, further analyses have shown its distribution in different licorice species, extending its known distribution among licorice species and suggesting a broader role in secondary metabolism. Nevertheless, the complex chemical synthesis of LCA presents challenges in regioselectivity control. The oral bioavailability of LCA is limited due to the intestinal first-pass effect, and its metabolic mechanism has not yet been fully elucidated. These issues restrict the therapeutic effects and practical applications of LCA in vivo. In recent years, advancements in optimizing synthetic pathways and developing new delivery systems have significantly improved the efficacy of LCA while also achieving notable breakthroughs in its safety. This review examines the distribution patterns, synthesis methods, in vivo metabolic processes, pharmacological activities, and current application status of LCA, while also exploring future research directions. However, its metabolic mechanisms and prospects for clinical application still require further investigation in the future. A multisource database search related literature employed \"Licochalcone A\"as the anchor term, synergized with species taxonomy (Glycyrrhiza), biogeographic patterns, and phytochemical dynamics (biosynthesis/metabolism).</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945906","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":"Bioactive Herbs for Liver Disorders: A Phyto-Pharmacological Review.","authors":"Poonam Sahu, Trilochan Satapathy","doi":"10.2174/0113892002381436250721200746","DOIUrl":"https://doi.org/10.2174/0113892002381436250721200746","url":null,"abstract":"<p><strong>Introduction: </strong>This review aims to explore the therapeutic potential and safety of herbal biactive compounds in the treatment of various liver disorders. As the liver plays a critical role in digestion, detoxification, energy storage, and protein synthesis, any impairment in its function can lead to significant health complications. The study aims to identify effective herbal agents that may support liver health.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using scientific databases and platforms including Web of Science, Scopus, PubMed, HINARI, ScienceDirect, and Google Scholar. The review includes studies that investigate the hepatoprotective potential of herbal bioactives, while research related to hepatic cancers was excluded to maintain a focus on non-malignant liver disorders.</p><p><strong>Results: </strong>The review identifies several medicinal plants and their active constituents that exhibit hepatoprotective properties. These bioactives function through various pharmacological mechanisms at the molecular level. Common liver conditions addressed include fatty liver, hepatitis, fibrosis, steatosis, and cirrhosis. The reviewed compounds demonstrate antioxidant, anti-inflammatory, and antifibrotic activities, supporting their role in liver disease management.</p><p><strong>Discussion: </strong>The findings support growing evidence that herbal bioactives can modulate key molecular pathways involved in liver disorders. These results align with existing studies highlighting the benefits of plant-based treatments. However, the limitations include a lack of clinical trial data, poor bioavailability of some compounds, and the need for standardized formulations. Further research is necessary to validate these results in human populations.</p><p><strong>Conclusion: </strong>Herbal bioactives such as flavonoids, polyphenols, alkaloids, glycosides, saponins, vitamins, and essential oils show promising hepatoprotective effects. This review emphasizes the importance of understanding their precise molecular mechanisms and ADME (absorption, distribution, metabolism, and excretion) profiles. These insights are crucial for developing safe, effective, and standardized herbal therapies for liver disease management.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945898","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":"m6A Modified-CYP1B1 Promotes HCC Cell Proliferation by Inhibiting Ferroptosis.","authors":"Wenwen Huang, Haihong Hu, Sheng Cai, Xiaoli Zheng, Su Zeng","doi":"10.2174/0113892002387502250714112923","DOIUrl":"https://doi.org/10.2174/0113892002387502250714112923","url":null,"abstract":"<p><strong>Introduction: </strong>CYP1B1, a crucial drug-metabolizing enzyme, metabolizes both endogenous compounds and clinical drugs. The present study investigated the effects of CYP1B1 on the proliferation, migration, apoptosis, and ferroptosis of HCC cells. It further elucidated the regulatory role of m⁶A modification, particularly via the methyltransferase METTL14-in regulating CYP1B1 mRNA stability and translation efficiency.</p><p><strong>Methods: </strong>CCK-8, colony formation, wound healing, and transwell assays were employed to assess the role of CYP1B1 in HCC cell proliferation and migration. Ferroptosis-related assays, Western blot analysis, RNA immunoprecipitation, and RNA stability assays were conducted to elucidate the underlying molecular mechanisms. The Hepatocellular Carcinoma Database (HCCDB) was utilized for gene expression analysis of CYP1B1 and METTL14.</p><p><strong>Results: </strong>Upregulated CYP1B1 in HCC inhibits ferroptosis and promotes cell proliferation by mediating GPX4, without significantly affecting HCC cell migration or apoptosis. METTL14-mediated m⁶A modification negatively regulates CYP1B1 expression in HCC. Specifically, METTL14 (downregulated in HCC) catalyzes m6A methylation of CYP1B1 mRNA, reducing its stability, while YTHDF3 binds to CYP1B1 mRNA to decrease its expression.</p><p><strong>Discussion: </strong>These findings established a functional link between drug metabolism, m⁶A epigenetics, and iron-dependent cell death in HCC, highlighting CYP1B1 and its upstream m⁶A machinery as potential targets for developing precision therapies that enhance ferroptosis sensitivity in HCC. The clinical relevance of the identified molecular mechanisms necessitates additional in-depth exploration.</p><p><strong>Conclusion: </strong>CYP1B1 promotes HCC cell proliferation by regulating GPX4-mediated ferroptosis resistance, while METTL14-mediated m6A modification serves as a key negative regulatory mechanism for CYP1B1. Targeting CYP1B1 as a therapeutic strategy holds substantial promise for future drug development in HCC.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854822","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":"Influence of Orange Oil on Skin Permeability, Dermatokinetics, and In Vivo Anti-inflammatory Properties of Lornoxicam-loaded Niosomal Gel.","authors":"Narahari N Palei, Arghya K Dhar, Jayaraman Rajangam, Dharani Prasad P, Biswa Mohan Sahoo","doi":"10.2174/0113892002368281250630073115","DOIUrl":"https://doi.org/10.2174/0113892002368281250630073115","url":null,"abstract":"<p><strong>Introduction: </strong>Lornoxicam is a non-steroidal anti-inflammatory drug belonging to the oxicam class. This study aimed to develop a niosomal gel containing orange oil for improving the anti-inflam-matory effect of lornoxicam.</p><p><strong>Methods: </strong>Lornoxicam-loaded niosomes (LOR-OR-NIO) were prepared using film hydration followed by the sonication method. Particle size, entrapment efficiency, and ex vivo permeation were all consid-ered during the optimization of the niosomal gels by employing the Box-Behnken design. Dermatoki-netics and in vivo anti-inflammatory studies were performed using male Wistar rats.</p><p><strong>Results: </strong>The particle size, entrapment efficiency, and skin permeation ability of the optimized LOR-OR-NIO formulation were found to be 354.3 nm, 83.56 %, and 105.63 μg/cm2, respectively. The ex vivo studies indicated that the optimized LOR-OR-NIO gel demonstrated superior drug penetration properties (105.43 μg/cm2) compared to both the LOR-NIO gel (69.23 μg/cm2) and the LOR gel (35.34 μg/cm2). The activation energy values of LOR gel, LOR-NIO gel, and LOR-OR-NIO gel were 2.74 Kcal mol-1, 1.93 Kcal mol-1, and 0.94 Kcal mol-1, respectively.</p><p><strong>Discussion: </strong>The lower activation energy of the LOR-OR-NIO gel contributed to more skin penetration of the drug. Dermatokinetics investigation demonstrated that the LOR-OR-NIO gel had superior pene-tration in the epidermal and dermal areas compared to the LOR gel. In vivo anti-inflammatory studies indicated that the LOR-OR-NIO gel exhibited greater edema inhibition compared to both the LOR-NIO gel and LOR gel. These results demonstrated the enhanced anti-inflammatory activity of the LOR-OR-NIO gel.</p><p><strong>Conclusion: </strong>The study concluded that orange oil enhanced skin permeability and influenced the derma-tokinetics of the LOR-OR-NIO gel, leading to an improvement in in vivo anti-inflammatory properties..</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816029","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}