Current Drug Metabolism[JOURNAL]
Sun
200 papers
Bioactive Herbs for Liver Disorders: A Phyto-Pharmacological Review.
Sahu P, Satapathy T
Curr Drug Metab · 2025 · PMID 40849767 · Publisher ↗
INTRODUCTION: This review aims to explore the therapeutic potential and safety of herbal bioactive compounds in the treatment of various liver disorders. As the liver plays a critical role in digestion, detoxification, e...
INTRODUCTION: This review aims to explore the therapeutic potential and safety of herbal bioactive 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
mA Modified-CYP1B1 Promotes HCC Cell Proliferation by Inhibiting Ferroptosis.
Huang W, Hu H, Cai S … +2 more , Zheng X, Zeng S
Curr Drug Metab · 2025 · PMID 40814886 · Publisher ↗
INTRODUCTION: 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 fer...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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 mA methylation of CYP1B1 mRNA, reducing its stability, while YTHDF3 binds to CYP1B1 mRNA to decrease its expression. DISCUSSION: 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. CONCLUSION: CYP1B1 promotes HCC cell proliferation by regulating GPX4-mediated ferroptosis resistance, while METTL14-mediated mA 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.
Influence of Orange Oil on Skin Permeability, Dermatokinetics, and Anti-inflammatory Properties of Lornoxicam-loaded Niosomal Gel.
Palei NN, Dhar AK, Rajangam J … +2 more , P DP, Sahoo BM
Curr Drug Metab · 2025 · PMID 40785180 · Publisher ↗
INTRODUCTION: 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-inflammatory effect of lornoxicam....
INTRODUCTION: 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-inflammatory effect of lornoxicam. METHODS: Lornoxicam-loaded niosomes (LOR-OR-NIO) were prepared using film hydration followed by the sonication method. Particle size, entrapment efficiency, and permeation were all considered during the optimization of the niosomal gels by employing the Box-Behnken design. Dermatokinetics and anti-inflammatory studies were performed using male Wistar rats. RESULTS: The particle size, entrapment efficiency, and skin permeation ability of the optimized LOR-ORNIO 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/cm) compared to both the LOR-NIO gel (69.23 μg/cm) and the LOR gel (35.34 μg/cm). The activation energy values of LOR gel, LOR-NIO gel, and LOR-OR-NIO gel were 2.74 Kcal mol, 1.93 Kcal mol, and 0.94 Kcal mol, respectively. DISCUSSION: 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 penetration in the epidermal and dermal areas compared to the LOR gel. 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-ORNIO gel. CONCLUSION: The study concluded that orange oil enhanced skin permeability and influenced the dermatokinetics of the LOR-OR-NIO gel, leading to an improvement in anti-inflammatory properties.
Advancing Liposomal Drug Delivery through Physiologically-Based Pharmacokinetic Modeling.
Braz HFG, Borges GSM, Lages EB
Curr Drug Metab · 2025 · PMID 40755096 · Publisher ↗
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Moonlighting Proteins: Unveiling Their Multifunctionality in Metabolic Regulation and Drug Discovery.
Prajapati S, Singh AP, Bhadouria N
Curr Drug Metab · 2025 · PMID 40735983 · Publisher ↗
Moonlighting proteins, defined by their ability to perform distinct, independent functions beyond their primary roles, have garnered attention in metabolic regulation and drug discovery. This review highlights the emergi...
Moonlighting proteins, defined by their ability to perform distinct, independent functions beyond their primary roles, have garnered attention in metabolic regulation and drug discovery. This review highlights the emerging significance of these proteins in diverse physiological and pathological processes. With examples like glycolytic enzymes and Krebs cycle components, we explore their involvement in transcriptional regulation, immune responses, and stress modulation. Their unique ability to mediate host-pathogen interactions and disease progression underscores their potential as therapeutic targets. Advanced technologies, such as proteomics and bioinformatics, have revolutionized the identification and characterization of these proteins, unraveling their structural and functional complexities. This synthesis aims to bridge gaps in understanding protein multifunctionality and advocates its implications in drug development. By targeting specific functions of moonlighting proteins while preserving their essential roles, new strategies in pharmacology and personalized medicine are envisioned. The review also proposes a roadmap for leveraging these proteins' multifunctionality to address current challenges in therapeutic interventions.
Oral Metronomic Formulation of Carboplatin Loaded PEGylated- MWCNTs: HPLC Method Validation and Pharmacokinetic Studies in Rabbit's Plasma.
Sharma S, Kuotsu K, Naskar S
Curr Drug Metab · 2025 · PMID 40698687 · Publisher ↗
BACKGROUND: Carboplatin (CP) is a widely used chemotherapeutic agent with poor oral bioavailability and potential systemic toxicity when administered intravenously. There is a growing interest in developing sustained-rel...
BACKGROUND: Carboplatin (CP) is a widely used chemotherapeutic agent with poor oral bioavailability and potential systemic toxicity when administered intravenously. There is a growing interest in developing sustained-release oral formulations to improve therapeutic efficacy and patient compliance. OBJECTIVE: The present study aimed to develop and evaluate an oral, enteric-coated, PEGylated multi-walled carbon nanotube (MWCNT) formulation (F2) of carboplatin and assess its pharmacokinetic and histopathological profile in comparison with the marketed intravenous product, Kemocarb®. METHODS: A sensitive and robust HPLC method was developed for the quantification of CP in rabbit plasma. Stability studies were performed at 4 °C for 4 hours and -80°C for 4 weeks. Histopathological evaluation was conducted on major organs of mice to assess toxicity. CP and caffeine were extracted with minimal matrix interference. Pharmacokinetic studies were performed following oral administration of the F2 formulation and compared with Kemocarb®. RESULTS: The developed HPLC method demonstrated good sensitivity, accuracy, and robustness. CP was stable under both short-term and long-term storage conditions. Histological analysis revealed no significant pathological damage in mice organs. The F2 formulation exhibited sustained drug release for up to 24 hours. The Tmax, Cmax, and MRT of CP for F2 were different compared to Kemocarb®, with a relative bioavailability of 1.182 ± 0.24. The Cmax and MRT of F2 were 12.327 ± 0.03* and 3.5805 ± 0.26 h, respectively. CONCLUSION: The developed F2 formulation of carboplatin demonstrates sustained release and improved relative bioavailability following oral administration. It may offer a promising alternative to commercial intravenous CP injections (Kemocarb®), potentially supporting metronomic chemotherapy strategies with improved patient compliance and reduced systemic toxicity.
Unexpected Clinically Significant Drug-Drug Interaction between Tacrolimus and Metronidazole in the Early Period after Renal Transplantation: A Literature Review.
Xiao Y, Zou H, Han X … +11 more , Zheng C, Yin C, Jiang Z, Zou S, Du A, Deng N, Li G, Ye S, Guo X, Zhong L, He J
Curr Drug Metab · 2025 · PMID 40660431 · Publisher ↗
INTRODUCTION: Drug interactions necessitate careful consideration in clinical practice. It is imperative for clinicians and pharmacists to monitor drug exposure and the co-administration of medications promptly in order...
INTRODUCTION: Drug interactions necessitate careful consideration in clinical practice. It is imperative for clinicians and pharmacists to monitor drug exposure and the co-administration of medications promptly in order to avert adverse outcomes and achieve optimal efficacy. OBJECTIVES: The prevalence of oral lesions varies from 28% to 60% in the short term after renal transplantation. The clinical use of metronidazole in the treatment of anaerobic bacterial infections among solid organ transplant recipients has been complicated by the potentially significant and unpredictable drug-drug interactions. METHODS: We present an unexpected clinically significant drug-drug interaction between tacrolimus and metronidazole in the early period after renal transplantation and describe the potential mechanism and clinical characteristics of this drug-drug interaction through a literature review. RESULTS: A 34-year-old female experienced a 65% increase in dose-normalized tacrolimus trough concentration after intravenous administration of metronidazole at 1000 mg/day for 8 days. When metronidazole was switched from intravenous to oral for 5 days, dose-normalized tacrolimus trough concentration was still increased by 52.4%. The magnitude of tacrolimus-metronidazole drug-drug interaction seems to be contingent upon the dose of metronidazole and the route of metronidazole administration. After cessation of metronidazole for one month, this drug-drug interaction, as assessed by weight-normalized tacrolimus dose, may still persist. CONCLUSION: In the early period following renal transplantation, the long-term concomitant use of metronidazole is likely to elevate the trough concentration of tacrolimus. Gene screening for CYP3A5*3/*3 and ABCB1 3435C>T in recipients of solid organ transplants may support individualized tacrolimus prescribing and facilitate the mitigation of risks associated with drug-drug interactions.
The Magic of Drug Targeting Is "Secretly" Tied to Optimal Drug Distribution and Exposure.
Hu M
Curr Drug Metab · 2025 · PMID 40621759 · Publisher ↗
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Synthesis and Antimicrobial Activity of Silver/Copper Oxide/Clay Hybrid Nanocomposites Against Gram-Positive and Gram-Negative Bacteria.
Fardin M, Sadr N, Rezvani A … +2 more , Hajhosseinjavaheri F, Dalghi E
Curr Drug Metab · 2025 · PMID 40600534 · Publisher ↗
BACKGROUND: The rapid surge in bacterial resistance to classical antibiotics and antimicrobial agents has driven researchers to identify new classes of antimicrobial agents. At the nanoscale, nanotechnological progress h...
BACKGROUND: The rapid surge in bacterial resistance to classical antibiotics and antimicrobial agents has driven researchers to identify new classes of antimicrobial agents. At the nanoscale, nanotechnological progress has strongly underscored the application of silver and copper since they present high antimicrobial activities toward gram-positive and gram-negative bacteria. Nanostructures containing these two elements-all the more so for hybrid nanocomposites-have been scantily the subject of investigated. The present work aims to develop and study a silver/copper oxide/clay hybrid nanocomposite. METHODS: Nanocomposites of silver, copper oxide, and their hybrid with clay were synthesized via chemical precipitation under controlled pH (9-11) and temperature (60-90°C) conditions. The antibacterial activity was assessed using standard 0.5 McFarland-adjusted bacterial inocula. Characterization was performed using FTIR, XRD, FESEM, and TEM techniques. MIC and MBC were determined through serial dilution, and data were analyzed using one-way ANOVA and Tukey's test (SPSS v26). RESULTS: The results indicated that the fabricated nanocomposite was impure, with nanosilver particles measuring 30-40 nm and copper oxide particles measuring 200-250 nm. The morphological properties of synthesized Ag/CuO/clay nanocomposites were evaluated using X-ray diffractometer analysis. The minimum inhibitory concentration (MIC) of the hybrid nanocomposite against and was 1024 μg/ml, and for and 2048 μg/ml. The minimum bactericidal concentration (MBC) against Staphylococcus aureus and Bacillus subtilis was 4096 μg/ml, and for Escherichia coli 4096 μg/ml, and 8192 μg/ml. DISCUSSION: Silver/copper oxide/clay hybrid nanocomposite exhibited more intensive antibacterial activities towards gram-positive bacteria in the absence of single-component nanocomposites, validating the synergistic effect of silver and copper in aid of clay. Its small efficacy on gram-negative strains also points at the necessity for additional optimization as well as extension. Such outcomes indicate the potential of the hybrid nanocomposite as an aspiring candidate for eventual antimicrobial applications. CONCLUSION: These results showed that the antimicrobial property of silver/copper/clay hybrid nanocomposite was better than copper/silver and clay nanocomposite against gram-positive bacteria, while showing a similar effect against gram-negative bacteria.
HFD-induced Alterations in Renal Tubular Oatp4c1-P-gp Transport Systems in Mice: Impact on Digoxin Renal Excretion and Gadolinium-Enhanced Radiological Manifestations.
Men J, Li J, Zhang T … +8 more , Chen Y, Xu B, Hou H, Sun L, Yue H, Duan Z, Gui T, Gai Z
Curr Drug Metab · 2025 · PMID 40600533 · Full text
OBJECTIVE: The clearance of digoxin in obese patients with renal impairment is reduced, leading to elevated serum concentrations and increased risks of digoxin toxicity. However, the exact mechanism of such alterations i...
OBJECTIVE: The clearance of digoxin in obese patients with renal impairment is reduced, leading to elevated serum concentrations and increased risks of digoxin toxicity. However, the exact mechanism of such alterations in obese patients remains unclear. Previous studies have suggested that the organic anion transporting polypeptide 4c1 (Oatp4c1, Slco4c1) mediates the elimination of digoxin at the basal membrane of the proximal tubule (PT), indicating its potential role in the pharmacokinetic changes in obese patients. This study aims to investigate the effects of a high-fat diet HFD on digoxin pharmacokinetics and transporter expression in mouse models and further analyze its significance by detecting the expression of transporters in human renal tissue samples. METHODS: First, HFD-induced obese mouse model was established. Mice were intraperitoneally injected with digoxin, and 24-hour urine samples and blood samples at five time points were collected. Pharmacokinetic evaluation was performed using liquid chromatography-tandem mass spectrometry. Renal pathological changes and the expression of digoxin transporters (Oatp4c1 and P-glycoprotein (P-gp)) were assessed using histological staining, Western blots (WB), as well as quantitative polymerase chain reaction (qPCR). Human renal pathologic alterations and expression of transporter proteins showed consistency with the results of animal experiments. To explore the potential use of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) as a marker for Oatp4c1 function, drug interactions between digoxin and Gd-EOBDTPA were assessed in mice. RESULTS: HFD-induced obese mice showed significant increases in body weight, blood glucose, and triglyceride, along with elevated blood concentration of digoxin, increased areas under the curve, reduced renal clearance rate (CLr), and prolonged half-life (t1/2). Histological staining revealed proximal tubular epithelial cell detachment and slight fibrosis in the kidney of the HFD group, with decreased expression of villin, the protein marker for PT. Immunofluorescent staining and Western blots for digoxin transporters showed a significant reduction of Oatp4c1 and P-gp proteins, suggesting that the renal elimination of digoxin was affected by the reduced level of Oatp4c1 and P-gp proteins. Co-administration of digoxin and Gd-EOB-DTPA resulted in a reduced clearance of Gd-EOB-DTPA, suggesting that both share the same transporter. The blood concentration of Gd-EOB-DTPA was higher (77.5%) in the HFD group. Renal magnetic resonance imaging (MRI) intensity was lower in the HFD group after Gd-EOB-DTPA administration compared to the Chow group. CONCLUSION: Obesity-induced kidney damage results in decreased Oatp4c1 and P-gp expression and function in PT, resulting in a reduction of digoxin renal clearance. The inhibition of Gd-EOB-DTPA clearance by digoxin co-administration and the increased Gd-EOB-DTPA blood concentration in the HFD group both suggest its potential use in characterizing the Oatp4c1 function .
A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine.
Xie Y, Zhang W, Rui Z … +3 more , Dai Y, Xing J, Han J
Curr Drug Metab · 2025 · PMID 40588993 · Publisher ↗
Piperaquine is an important partner drug in artemisinin-based combination therapy, which is highly effective for the treatment of uncomplicated malaria. Several studies have been reported on its pharmacokinetic profiles...
Piperaquine is an important partner drug in artemisinin-based combination therapy, which is highly effective for the treatment of uncomplicated malaria. Several studies have been reported on its pharmacokinetic profiles in different populations, as well as its bioanalytical methods. Piperaquine shows a very large volume of distribution (up to 877 l/kg), a low oral clearance (0.3-1.9 l/h/kg), and an extremely long terminal elimination half-life (up to 30 days) in both healthy volunteers and malarial patients. Piperaquine metabolism is primarily mediated by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C8. The oral bioavailability of piperaquine can be influenced by the consumption of high-fat food. The pharmacokinetics of piperaquine is affected by body weight, age, and pregnancy. Piperaquine has limited clinically relevant interactions with most commonly prescribed drugs. Plasma has been the most commonly studied matrix, and the most used pretreatment techniques involve protein precipitation. HPLC-UV and HPLC-MS/MS are usually used for the quantification of piperaquine in biological samples with researchers seeking a balance between affordability and sensitivity. This review summarizes the analytical assays used for the quantification of piperaquine in biological samples and its pharmacokinetic properties, with particular attention to information on food-drug interactions, drug-drug interactions, and pharmacokinetic characteristics in special populations, including pregnant women and children.
The Application of Artificial Intelligence in Drug ADME Research.
Yin J, Qi Y, Zhu F … +1 more , Zeng S
Curr Drug Metab · 2025 · PMID 40539355 · Publisher ↗
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Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation.
Daraghmeh DN, Salameh S, Zahdeh M … +2 more , Ghanem R, Karaman R
Curr Drug Metab · 2025 · PMID 40530733 · Publisher ↗
BACKGROUND: The female reproductive system is susceptible to oxidative stress, which can interfere with ovulation, menstrual cycles, egg quality, and tubal function, ultimately leading to infertility. Antioxidants might...
BACKGROUND: The female reproductive system is susceptible to oxidative stress, which can interfere with ovulation, menstrual cycles, egg quality, and tubal function, ultimately leading to infertility. Antioxidants might play a crucial role in protecting reproductive health by neutralizing Reactive Oxygen Species (ROS) and preventing cellular damage. OBJECTIVE: To provide an overview of the research that has been performed on the benefits of antioxidant supplementation for increasing female fertility. METHODS: We conducted a comprehensive search of PubMed, Embase, and Google for full-text, English-language publications between 2000 and 2023 that investigated the relationship between antioxidant supplementation and improvements in female fertility. RESULTS: Antioxidants have been investigated for their potential to improve fertility outcomes in subfertile women. Antioxidant supplementation shows promise in mitigating these effects by neutralizing excess ROS and restoring balance, leading to improved egg count and fertility outcomes. However, it is important to note that the effectiveness of antioxidant supplementation can vary depending on individual health factors and the specific antioxidants used. Studies suggest that a combination of antioxidants, such as vitamins C and E, selenium, and coenzyme Q10, may be more beneficial than single supplements. Although individual research has shown beneficial correlations between different antioxidant supplementation and female fertility, study repeatability is poor. As a result, further large-scale, well-designed clinical trials are necessary to better understand the precise role and optimal combinations of antioxidants for enhancing fertility in subfertile women. DISCUSSION AND CONCLUSION: This review study offers crucial insights into the complex connection between OS and female reproductive health. It highlights the potential advantages of antioxidant supplements as a preventative strategy. To enhance female fertility outcomes, further research, particularly randomized controlled clinical trials, is needed to determine best practices, identify populations that could benefit the most, and explore innovative antioxidant treatments.
A Gut Microbial Transformation-Integrated Network Pharmacology Approach to Elucidate the Therapeutic Mechanisms of Timosaponin AIII in Diabetes.
Zhang H, Wei J, Tian X … +6 more , Li W, Yang M, Zhang Q, Wang N, Jin Y, Du Y
Curr Drug Metab · 2025 · PMID 40511806 · Publisher ↗
OBJECTIVE: Timosaponin AIII, with poorly soluble characteristics, has a potential antidiabetic effect evaluated and . The major problem associated with poorly soluble drugs is very low bioavailability. This study aimed...
OBJECTIVE: Timosaponin AIII, with poorly soluble characteristics, has a potential antidiabetic effect evaluated and . The major problem associated with poorly soluble drugs is very low bioavailability. This study aimed to investigate the metabolic profiles and antidiabetic mechanism of Timosaponin AIII. MATERIALS AND METHODS: The metabolic profiles of Timosaponin AIII in intestinal flora were analyzed using LC-MS/MS. Based on mass spectrometry analysis, network pharmacology combined with the GEO database was used to identify potential targets and elucidate the antidiabetic mechanism. Finally, the stability of compound- target complexes was further functionally confirmed by molecular docking. RESULTS: As a result, 13 metabolites were identified. After the compound-target network, the genes of its metabolites increased by 60 compared to those of Timosaponin AIII. Subsequently, 13 core targets related to antidiabetic efficacy were identified through PPI network analysis. Key genes EGFR, MAPK1, and ICAM1 with strong binding efficiencies with metabolites were identified as crucial targets for the therapeutic effects of Timosaponin AIII. The KEGG analysis indicated that timosaponin AIII combated diabetes through various signaling pathways, including PI3K-Akt, FoxO, and HIF-1 signaling pathways, etc. Conclusion: Taken together, this study clarified the mechanism of Timosaponin AIII against diabetes by identifying additional targets and pathways, and the importance of glycosidic structures. Otherwise, we might provide a solid foundation for the development of clinical applications of Timosaponin AIII.
Temperature-sensitive Hydrogel: An Effective Treatment for Nasal Drug Delivery Targeting the Brain.
Li D, Chen L, Chen Y … +3 more , Jiang L, Wang R, Li W
Curr Drug Metab · 2025 · PMID 40329725 · Publisher ↗
The brain is highly protected by physiological barriers, in which the blood-brain barrier restricts the entry of most drugs. Intranasal drug delivery is a non-invasive way of drug delivery, which can cross the blood-brai...
The brain is highly protected by physiological barriers, in which the blood-brain barrier restricts the entry of most drugs. Intranasal drug delivery is a non-invasive way of drug delivery, which can cross the blood-brain barrier and achieve direct and efficient targeted delivery to the brain. Therefore, it has great potential in application to the treatment of brain diseases. Temperature-sensitive hydrogels undergo a solutiongel transition with temperature change, and the gel form has good mucosal adsorption properties in the nasal cavity, which is commonly used for targeted delivery of drugs for brain diseases. In this article, by introducing the transport mechanism of brain targeting after nasal administration, combined with the prescription design and basic performance study of temperature-sensitive nasal hydrogel, we summarized the research on the role that temperature-sensitive hydrogel plays brain targeting after via nasal administration, aiming to provide a reference for the development of therapeutic drugs for cerebral diseases and their clinical application. A graphical summary.
Antioxidant Potential of Gallic Acid Prevents Di-2-ethyhexyl Phthalate-induced Inhibition of Osteogenic Differentiation.
Hussein AM, Mahrokh P
Curr Drug Metab · 2025 · PMID 40296616 · Publisher ↗
OBJECTIVE: Di-2-ethylhexylphthalate (DEHP) is utilized as a plasticizer in polyvinylchloride products (PVC). When medical devices like blood bags, tubes, and syringes are employed, DEHP leaches out of the PVC polymers an...
OBJECTIVE: Di-2-ethylhexylphthalate (DEHP) is utilized as a plasticizer in polyvinylchloride products (PVC). When medical devices like blood bags, tubes, and syringes are employed, DEHP leaches out of the PVC polymers and enters biological fluids through non-covalent binding. The presence of DEHP in peripheral blood leads to contamination of bone marrow. Previous research has demonstrated that this chemical induces oxidative stress, which adversely affects the viability and osteo-differentiation of bone marrow mesenchymal stem cells (BMSCs). Hence, our current study aims to utilize gallic acid (GA), a natural antioxidant, to alleviate the inhibitory effects of DEHP on BMSCs' osteogenic differentiation. MATERIALS AND METHODS: In osteogenic media, BMSCs extracted from Wistar rats were treated with 0.25 μM of GA and 100 μM of DEHP individually and in combination for 20 days. Then viability, total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD), alkaline phosphatase activity, production of collagen1A1 protein as well as expression of Bmp2 and 7, Smad1, Runx2, Oc, Alp, Col-1a1 genes were investigated. RESULTS: The viability and differentiation ability of BMSCs was significantly (p<0.0001) decreased by DEHP, while GA significantly (P<0.0001) ameliorated the effect of DEHP. DEHP caused a significant decrease (P<0.0001) in the total protein and collagen-1A1 concentration, TAC and activity of antioxidant enzymes, but significantly (P<0.001) increased MDA level. In addition, DEHP caused a significant decrease in the expression of osteo-related genes. In the co-treatment group, GA mitigated the toxic effects of DEHP compared to the control group by inhibiting DEHP-induced oxidative stress and enhancing cell viability and osteo-differentiation properties. CONCLUSION: These results confirm that GA reduces the negative effects of DEHP on the osteo-differentiation of BMSCs at the cellular level. However, further studies are necessary to validate these findings.
A Data Mining Approach on Polypharmacy and Drug-drug Interactions of Common Diabetes Medications.
Dwivedi J, Kaushal S, Wal P … +4 more , Chandrashekhar DJ, Sharma A, Nathiya D, Gasmi A
Curr Drug Metab · 2025 · PMID 40248924 · Publisher ↗
BACKGROUND: When managing diabetes, polypharmacy the use of several drugs simultaneously to obtain the best possible glucose control is typical. Drug-drug interactions (DDIs), which can result in side effects and reduced...
BACKGROUND: When managing diabetes, polypharmacy the use of several drugs simultaneously to obtain the best possible glucose control is typical. Drug-drug interactions (DDIs), which can result in side effects and reduced treatment efficacy, have increased. OBJECTIVES: This study evaluated the data mining approach of polypharmacy-based drug-drug interactions for common diabetes medication. METHODS: To identify publications that met the inclusion criteria, several scientific reviews and research papers were searched, including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and NCBI, using keywords such as diabetes, drug-drug interaction, polypharmacy, data mining, and herbal interaction. RESULTS: Many important drug-drug interactions among popular anti-diabetic drugs have been identified using data mining. Using iodinated contrast media and metformin together increased the risk of lactic acidosis, and using NSAIDs and sulfonylureas simultaneously increased the risk of hypoglycemia. A higher incidence of DDIs was found in an analysis of elderly individuals and those with several comorbidities. Predictive models have demonstrated high sensitivity and accuracy in detecting possible DDIs from patient and drug data. CONCLUSION: Finding and evaluating DDIs in polypharmacy related to diabetes care are made possible through data mining. These results could potentially improve patient safety by influencing more individualized and cautious prescription techniques. The improvement of these methods and their application in standard clinical practice should be the main goal of future studies.
Rapid and Comprehensive Identification of Vincosamide Metabolites and in Rats by Ultra-high Performance Liquid Chromatography-Quadrupole-Exactive Orbitrap-high Resolution Mass Spectrometry.
Gao A, Wang H, Cheng X … +2 more , Li C, Sun L
Curr Drug Metab · 2025 · PMID 40247802 · Publisher ↗
BACKGROUND: Vincosamide, an indole alkaloid extracted from , exhibits a range of pharmacological activities, such as anti-tumor, antibacterial, and anti-inflammatory properties. However, despite its promising therapeutic...
BACKGROUND: Vincosamide, an indole alkaloid extracted from , exhibits a range of pharmacological activities, such as anti-tumor, antibacterial, and anti-inflammatory properties. However, despite its promising therapeutic applications, there is a notable gap in research focused on the metabolic pathways of vincosamide. OBJECTIVES: This study aims to investigate the metabolism of vincosamide both and in rats, and to elucidate its metabolic pathways. METHODS: Samples of liver microsomal incubation, plasma, bile, urine, and feces following vincosamide administration were analyzed by ultra-high performance liquid chromatography-quadrupole-Exactive Orbitraphigh resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS). The collected data were analyzed using Compound Discovery 3.2 software and the molecular network method. The metabolites identified through these methodologies were subsequently validated using Xcalibur 4.1 software, which provided information on retention times, parent ions, and characteristic fragment ions. RESULTS: A total of 37 metabolites were identified, including 8 and 32 in vivo (3 in plasma, 7 in bile, 22 in urine, and 17 in feces). While the metabolism of vincosamide differs in vitro and in rats, the type of metabolic reaction that occurs is well-defined. The predominant metabolic pathways are oxidation, reduction, deglycosylation, hydration, glucuronidation, methylation, sulfation, glycine conjugation, cysteine conjugation, taurine conjugation, and complex reactions. CONCLUSION: This study elucidates the metabolism of vincosamide and in rats, thereby expanding the metabolite profile of vincosamide. These findings provide a foundation for the potential development of new drugs based on vincosamide.
Expression, Function, and Regulation of ABCG2 on the Intestinal Epithelial Barrier Permeability.
Shi P, Tang L, Yin F … +2 more , Guo H, Liu J
Curr Drug Metab · 2025 · PMID 40231523 · Publisher ↗
Human breast cancer resistance protein (BCRP, gene symbol ABCG2) is an ATP-binding cassette (ABC) efflux transporter that is highly expressed on the apical membranes of intestinal epithelium and contributes to the absorp...
Human breast cancer resistance protein (BCRP, gene symbol ABCG2) is an ATP-binding cassette (ABC) efflux transporter that is highly expressed on the apical membranes of intestinal epithelium and contributes to the absorption, distribution, and elimination of xenobiotics and the efflux of endogenous molecules. Also, the intestinal epithelial monolayer is the largest interface and the most important functional barrier between the internal environment and the systemic circulation. Extensive studies have demonstrated that intestinal ABCG2 of humans and rodents plays a crucial role in limiting absorption of xenobiotics, which are ABCG2 transport substrates, in the small intestine by mediating distribution in the intestinal epithelial barrier. Therefore, changes in the expression, function and activity of ABCG2 in the intestinal epithelial barrier play important roles in drug response and side effects. In this review, we specifically summarize the current research progress of ABCG2 in intestinal drug transport, intestinal urate excretion and intestinal barrier dysfunction, and its role in altering the intestinal epithelial barrier permeability in human intestinal disorder.
Exploring the Gut-brain Axis: Microbiome Contributions to Pathophysiology of Attention Deficit Hyperactivity Disorder and Potential Therapeutic Strategies.
Phatak M, Nair B, Soni U … +1 more , Pujari R
Curr Drug Metab · 2025 · PMID 40207768 · Publisher ↗
Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity, significantly impacting individuals' daily functioning...
Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity, significantly impacting individuals' daily functioning and quality of life. This manuscript explores the intricate relationship between the gut microbiome and ADHD, emphasizing the role of the gut-brain axis, a bidirectional communication pathway linking the central nervous system (CNS) and the gastrointestinal tract (GIT). The composition of gut microbiota influences several physiological processes, including immune function, metabolism, and the production of neuroactive metabolites, which are critical for cognitive functions such as memory and decision-making. The review discusses alternative therapeutic options, including dietary modifications, synbiotics, and specific diets like the ketogenic diet, which may offer promising outcomes in managing ADHD symptoms. Further research is necessary to establish the efficacy and mechanisms of action of synbiotics and dietary interventions, despite preliminary studies suggesting their potential benefits. This review article aims to provide a comprehensive overview of the current understanding of the gut microbiome's impact on ADHD, highlighting the need for continued investigation into innovative treatment strategies that leverage the gut-brain connection.
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