Current drug metabolism最新文献

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).

Introduction: 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.

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.

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 m6A 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 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.

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-inflam-matory 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 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.

Results: 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.

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 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.

Conclusion: 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..

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 exam-ples 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 interac-tions 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 personal-ized medicine are envisioned. The review also proposes a roadmap for leveraging these proteins' multifunc-tionality to address current challenges in therapeutic interventions.

Background: Carbon nanotubes (CNTs) have emerged as promising nanocarriers in drug delivery due to their unique physicochemical properties and biocompatibility.

Objective: This study aims to explore the potential of oral sustained-release metronomic drug delivery formulations of carboplatin (CP), a widely used antitumor prodrug, utilizing carbon nanotubes as carriers.

Methods: A comprehensive literature review was conducted using PubMed and Scopus databases, covering studies published between the years 2010 and 2024, focusing on CNT-based drug delivery systems and their application in cancer therapeutics.

Results: CNTs have demonstrated significant potential in terms of high drug loading efficiency, targeted drug delivery, improved pharmacokinetics, and enhanced bioavailability. Several studies have also highlighted their utility in sustained and controlled drug release, which is critical for metronomic chemotherapy.

Conclusion: Carbon nanotube-based drug delivery systems represent a promising platform for the development of oral sustained metronomic formulations of carboplatin. However, further research is needed to address concerns related to toxicity, biodegradability, and regulatory acceptance before clinical translation.

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.

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/Cu2O/clay nanocomposites were evaluated using X-ray diffractometer analysis. The minimum inhibitory concentration (MIC) of the hybrid nanocomposite against Staphylococcus aureus and Bacillus subtilis was 1024 μg/ml, and for Escherichia coli and Pseudomonas aeruginosa 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 Pseudomonas aeruginosa 8192 μg/ml.

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.

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-lan-guage publications between 2000 and 2023 that investigated the relationship between antioxidant supplemen-tation 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, se-lenium, 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 un-derstand the precise role and optimal combinations of antioxidants for enhancing fertility in subfertile women.

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 strat-egy. 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.