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Volume 25, Issue 3, 2024
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Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment
Authors: Asad Ahmad, Juber Akhtar, Mohammad Ahmad, Anas Islam, Badruddeen, Mohammad I. Khan, Shaiber Siddiqui and Akash SrivastavaCurcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.
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Association of UGT1A Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients
Authors: Jingwen Yuan, Shuang Fei, Zeping Gui, Zijie Wang, Hao Chen, Li Sun, Jun Tao, Zhijian Han, Xiaobing Ju, Ruoyun Tan, Min Gu and Zhengkai HuangBackground: BK virus (BKV) infection is an opportunistic infectious complication and constitutes a risk factor for premature graft failure in kidney transplantation. Our research aimed to identify associations and assess the impact of single-nucleotide polymorphisms (SNPs) on metabolism-related genes in patients who have undergone kidney transplantation with BKV infection. Material/Methods: The DNA samples of 200 eligible kidney transplant recipients from our center, meeting the inclusion criteria, have been collected and extracted. Next-generation sequencing was used to genotype SNPs on metabolism-associated genes (CYP3A4/5/7, UGT1A4/7/8/9, UGT2B7). A general linear model (GLM) was used to identify and eliminate confounding factors that may influence the outcome events. Multiple inheritance models and haplotype analyses were utilized to identify variation loci associated with infection caused by BKV and ascertain haplotypes, respectively. Results: A total of 141 SNPs located on metabolism-related genes were identified. After Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) analysis, 21 tagger SNPs were selected for further association analysis. Based on GLM results, no confounding factor was significant in predicting the incidence of BK polyomavirus-associated infection. Then, multiple inheritance model analyses revealed that the risk of BKV infection was significantly associated with rs3732218 and rs4556969. Finally, we detect significant associations between haplotype T-A-C of block 2 (rs4556969, rs3732218, rs12468274) and infection caused by BKV (P = 0.0004). Conclusion: We found that genetic variants in the UGT1A gene confer BKV infection susceptibility after kidney transplantation.
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Avapritinib Carries the Risk of Drug Interaction via Inhibition of UDP-Glucuronyltransferase (UGT) 1A1
Authors: Xin Lv, Zhen Wang, Zhe Wang, Hang Yin, Yangliu Xia, Lili Jiang and Yong LiuBackground: Avapritinib is the only drug for adult patients with PDGFRA exon 18 mutated unresectable or metastatic gastrointestinal stromal tumor (GIST). Although avapritinib has been approved by the FDA for four years, little is known about the risk of drug-drug interactions (DDIs) via UDP-glucuronyltransferases (UGTs) inhibition. Objective: The aim of the present study was to systematically evaluate the inhibitory effects of avapritinib against UGTs and to quantitatively estimate its potential DDIs risk in vivo. Methods: Recombinant human UGTs were employed to catalyze the glucuronidation of substrates in a range of concentrations of avapritinib. The kinetics analysis was performed to evaluate the inhibition types of avapritinib against UGTs. The quantitative prediction of DDIs was done using in vitro-in vivo extrapolation (IVIVE). Results: Avapritinib had a potent competitive inhibitory effect on UGT1A1. Quantitative prediction results showed that avapritinib administered at clinical doses might result in a 14.85% increase in area under the curve (AUC) of drugs primarily cleared by UGT1A1. Moreover, the Rgut value was calculated to be 18.44. Conclusion: Avapritinib has the potential to cause intestinal DDIs via the inhibition of UGT1A1. Additional attention should be paid when avapritinib is coadministered with UGT1A1 substrates.
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Comprehensive Analysis of Chemical Ingredients of Waiganfengsha Granule and Absorbed Components in Rat Plasma Based on UHPLC-Q-TOF-MS
Authors: Wei Wei, Liyuan Huang, Jun Huang, Jinhua Li, Yingying Qing, Xiaotao Hou and Wen LiuObjective: Waiganfengsha Granule, an over-the-counter drug, is commonly used for treating windheat cold and sore throat in clinical settings. However, its material basis of medicinal efficacy is still unclear. In this study, an efficient integrated analytical strategy was established for its chemical and metabolite profiles study. Methods: Firstly, to avoid the possible false-positive results of structural elucidation, an in-house component library that contains chemical constituents reported in the literature from the six individual medicines of Waiganfengsha Granule was established. Secondary, mass data post-processing techniques, including precursor ion list and neutral loss filtering, were applied to enhance the identification accuracy. Thirdly, for the rapid characterization of those absorbed components after oral administration in rats, the identified chemical constituents were used as candidate components for the serum analysis. By comparing the retention time and analyzing mass data, the metabolites in rat plasma were identified. Results: As a result, 57 chemical ingredients were identified, including 21 phenolic acids, 9 alkaloids, 2 flavonoids, 5 lignins, 13 saponins, and 7 other compounds. Among these, 12 compounds were unambiguously identified by comparison with reference standards, and 45 were tentatively characterized by analyzing their accurate MS data, MS/MS fragmentation patterns, and also by comparison with those data reported in the literature. Additionally, 46 metabolites were detected and identified in rat plasma. Conclusion: This study is beneficial for understanding the chemical composition and metabolic profiles of Waiganfengsha Granule, and the results obtained might provide a solid basis for further studies on its functional mechanism.
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Disposition Kinetics of Cathinone and its Metabolites after Oral Administration in Rats
Background: Cathinone is a natural stimulant found in the Catha edulis plant. Its derivatives make up the largest group of new psychoactive substances. In order to better understand its effects, it is imperative to investigate its distribution, pharmacokinetics, and metabolic profile. However, the existing literature on cathinone remains limited. Objective: This study aimed to investigate the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Methods: Cathinone and cathine concentrations were identified and quantified using ion trap liquid chromatography- mass spectrometry (LC-IT/MS). The metabolic profile in the serum, brain, lung, liver, kidney, and heart was analyzed at specific time points (0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours) using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method. Results: The highest concentration of cathinone was found in the kidney (1438.6 μg/L, which gradually decreased to 1.97 within 48 h and disappeared after 72 h. Cathinone levels in the lungs, liver, and heart were 859, 798.9, and 385.8 μg/L, respectively, within half an hour. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 μg/L and became undetectable after 24 h. In the rat brain, cathinone levels dropped quickly and were undetectable within six hours, decreasing from 712.7 μg/L after 30 min. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours, indicating slower conversion of cathinone to cathine in the brain and serum. Conclusion: This study revealed a dynamic interplay between cathinone disposition kinetics and its impact on organ-specific metabolic profiles in rats. These results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. Investigating the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine is essential for informed decision- making in medical practices and further research into the pharmacological properties of cathinone.
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Inhibition of Glycyrrhiza Polysaccharide on Human Cytochrome P450 46A1 in vitro and in vivo: Implications in Treating Neurological Diseases
Authors: Jie Du, Zujia Chen, Xiaodong Chen, Jiahui Zhang, Yaojun Wang, Tingting Zhao, Dalong Wang, Changyuan Wang, Yanwei Chen, Qiang Meng, Huijun Sun, Kexin Liu and Jingjing WuBackground: Cytochrome P450 (CYP) 46A1, also known as cholesterol 24S-hydroxylase, is essential for maintaining the homeostasis of cholesterol in the brain and serves as a therapeutic target of neurodegenerative disorders and excitatory neurotoxicity. N-methyl-d-aspartate receptor (NMDAR) is a prototypical receptor for the excitatory neurotransmitter glutamate and can be specifically regulated by 24S-hydroxycholesterol (24S-HC). Glycyrrhiza is one of the most widely used herbs with broad clinical applications, which has several pharmacological activities, such as clearing heat and detoxifying, moistening the lung and relieving cough, analgesic, neuroprotective outcomes, and regulating a variety of drug activities. Glycyrrhiza is a commonly used herb for the treatment of epileptic encephalopathy. However, whether glycyrrhiza can interfere with the activity of CYP46A1 remains unknown. Objective: This study aimed to investigate the regulating effects of glycyrrhiza polysaccharides (GP) on CYP46A1-mediated cholesterol conversion, as well as in the modulation of related proteins. Materials and Methods: The effects of glycyrrhiza polysaccharide (GP) on the activity of CYP46A1 were investigated in vivo and in vitro. Moreover, the potential regulatory effects of GP on the expressions of CYP46A1, HMG-CoA reductase (HMGCR), and NMDAR were also detected. Results: The in vitro results demonstrated that glycyrrhiza polysaccharide (GP), as the main water-soluble active component of glycyrrhiza, remarkably inhibited the activity of CYP46A1 in a non-competitive mode with a Ki value of 0.7003 mg/ml. Furthermore, the in vivo experiments verified that GP markedly decreased the contents of 24S-HC in rat plasma and brain tissues as compared to the control. More importantly, the protein expressions of CYP46A1, GluN2A, GluN2B, and HMG-CoA reductase (HMGCR) in rat brains were all downregulated, whereas the mRNA expressions of CYP46A1 and HMGCR were not significantly changed after treatment with GP. Conclusion : GP exhibits a significant inhibitory effect on CYP46A1 activity in vitro and in vivo, and the protein expressions of CYP46A1, HMGCR, and NMDAR are also inhibited by GP, which are of considerable clinical significance for GP's potential therapeutic role in treating neurological diseases.
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Volumes & issues
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Volume 25 (2024)
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Volume 24 (2023)
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Volume 23 (2022)
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Volume 22 (2021)
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Volume 21 (2020)
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Volume 20 (2019)
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Volume 19 (2018)
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Volume 18 (2017)
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Volume 17 (2016)
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Volume 16 (2015)
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Volume 15 (2014)
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Volume 14 (2013)
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Volume 13 (2012)
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Volume 12 (2011)
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Volume 11 (2010)
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Volume 10 (2009)
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Volume 9 (2008)
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Volume 8 (2007)
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Volume 7 (2006)
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Volume 6 (2005)
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Volume 5 (2004)
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Volume 4 (2003)
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Volume 3 (2002)
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Volume 2 (2001)
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Volume 1 (2000)
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Comprehensive Metabolism Study of Tangeretin in Rat Plasma, Urine and Faeces Using Ultra-High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole- Orbitrap High-Resolution Accurate Mass Spectrometry
Authors: Xiaojun Yu, Zhufeng Cong, Changlin Wang, Shengguang Wang, Zhi Yan, Bin Wang, Xiaonan Liu, Zhen Li, Peng Gao and Huaixing Kang
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