Current drug metabolism最新文献

{"title":"Unraveling the Role of COMT Polymorphism in Dopamine-Mediated Vasopressor Effects: An Observational Cross-Sectional Study.","authors":"Kannan Sridharan, Anfal Jassim, Ali Mohammed Qader, Sheikh Abdul Azeez Pasha","doi":"10.2174/0113892002293952240315064943","DOIUrl":"10.2174/0113892002293952240315064943","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the association between rs4680 polymorphism in the COMT gene and the vasoconstrictive effects of commonly used vasopressors.</p><p><strong>Background: </strong>Dopamine is a medication that is given intravenously to critically ill patients to help increase blood pressure. Catechol O-Methyl Transferase (COMT) breaks down dopamine and other catecholamines. There is a genetic variation in the COMT gene called rs4680 that can affect how well the enzyme works. Studies have shown that people with this genetic variation may have different blood pressure levels. However, no one has looked at how this genetic variation affects the way dopamine works to increase blood pressure.</p><p><strong>Objectives: </strong>To investigate the impact of the rs4680 polymorphism in the COMT gene on the pharmacodynamic response to dopamine.</p><p><strong>Methods: </strong>Critically ill patients administered dopamine were included following the consent of their legally acceptable representatives. Details on their demographic characteristics, diagnosis, drug-related details, changes in the heart rate, blood pressure, and urinary output were obtained. The presence of rs4680 polymorphism in the COMT gene was evaluated using a validated method.</p><p><strong>Results: </strong>One hundred and seventeen patients were recruited, and we observed a prevalence of rs4680 polymorphism in 57.3% of our critically ill patients. Those with mutant genotypes were observed with an increase in the median rate of change in mean arterial pressure (mm Hg/hour) [wild: 8.9 (-22.6 to 49.1); heterozygous mutant: 5.9 (-34.1 to 61.6); and homozygous mutant: 19.5 (-2.5 to 129.2)] and lowered urine output (ml/day) [wild: 1080 (21.4 to 5900); heterozygous mutant: 380 (23.7 to 15800); and homozygous mutant: 316.7 (5.8 to 2308.3)].</p><p><strong>Conclusion: </strong>V158M (rs4680) polymorphism is widely prevalent in the population and was significantly associated with altered effects as observed clinically. This finding suggests valuable insights into the molecular basis of COMT function and its potential impact on neurotransmitter metabolism and related disorders. Large-scale studies delineating the effect of these polymorphisms on various vasopressors are the need of the hour.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174064","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":"Disposition Kinetics of Cathinone and its Metabolites after Oral Administration in Rats.","authors":"Fahad Y Sabei, Ibrahim Khardali, Mohamed A Al-Kasim, Emad Sayed Shaheen, Magbool Oraiby, Ahmad Alamir, Banji David, Saeed Alshahrani, Abdulmajeed M Jali, Mohammed Attafi, Mohammed Y Albeishy, Ibraheem Attafi","doi":"10.2174/0113892002300638240513065512","DOIUrl":"10.2174/0113892002300638240513065512","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944368","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":"Avapritinib Carries the Risk of Drug Interaction <i>via</i> Inhibition of UDP-Glucuronyltransferase (UGT) 1A1.","authors":"Xin Lv, Zhen Wang, Zhe Wang, Hang Yin, Yangliu Xia, Lili Jiang, Yong Liu","doi":"10.2174/0113892002288312240521092054","DOIUrl":"10.2174/0113892002288312240521092054","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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 <i>in vivo</i>.</p><p><strong>Methods: </strong>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 <i>in vitro-in vivo</i> extrapolation (IVIVE).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Avapritinib has the potential to cause intestinal DDIs <i>via</i> the inhibition of UGT1A1. Additional attention should be paid when avapritinib is coadministered with UGT1A1 substrates.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157928","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":"Safety Aspects of Herb Interactions: Current Understanding and Future Prospects.","authors":"Subhajit Hazra, Preet Amol Singh","doi":"10.2174/0113892002289753240305062601","DOIUrl":"10.2174/0113892002289753240305062601","url":null,"abstract":"<p><strong>Background: </strong>The use of herbal medicines is on the rise throughout the world due to their perceived safety profile. However, incidences of herb-drug, herb-herb and herb-food interactions considering safety aspects have opened new arenas for discussion.</p><p><strong>Objective: </strong>The current study aims to provide comprehensive insights into the various types of herb interactions, the mechanisms involved, their assessment, and historical developments, keeping herbal safety at the central point of discussion.</p><p><strong>Methods: </strong>The authors undertook a focused/targeted literature review and collected data from various databases, including Science Direct, Wiley Online Library, Springer, PubMed, and Google Scholar. Conventional literature on herbal remedies, such as those by the WHO and other international or national organizations.</p><p><strong>Results: </strong>The article considered reviewing the regulations, interaction mechanisms, and detection of herb-herb, herb-drug and herb-food interactions in commonly used yet vital plants, including <i>Glycyrrhiza glabra, Mentha piperita, Aloe barbadensis, Zingiber officinale, Gingko biloba, Withania somnifera, etc</i>. The study found that healthcare professionals worry about patients not informing them about their herbal prescriptions (primarily used with conventional treatment), which can cause herb-drug/herb-food/herb-herb interactions. These interactions were caused by altered pharmacodynamic and pharmacokinetic processes, which might be explained using <i>in-vivo, in-vitro, in-silico</i>, pharmacogenomics, and pharmacogenetics. Nutrivigilance may be the greatest method to monitor herb-food interactions, but its adoption is limited worldwide.</p><p><strong>Conclusion: </strong>This article can serve as a lead for clinicians, guiding them regarding herb-drug, herb-food, and herb-herb interactions induced by commonly consumed plant species. Patients may also be counseled to avoid conventional drugs, botanicals, and foods with a restricted therapeutic window.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119027","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":"Where will Medicines that Serve the Global South and Economically Disadvantaged People Come From?","authors":"Ming Hu","doi":"10.2174/138920022501240507141919","DOIUrl":"https://doi.org/10.2174/138920022501240507141919","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491227","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":"Association of <i>UGT1A</i> 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, Zhengkai Huang","doi":"10.2174/0113892002282727240307072255","DOIUrl":"10.2174/0113892002282727240307072255","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Material/methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>We found that genetic variants in the UGT1A gene confer BKV infection susceptibility after kidney transplantation.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174062","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":"The Metabolism of the New Benzodiazepine Remimazolam.","authors":"Wolfgang Schmalix, Karl-Uwe Petersen, Marija Pesic, Thomas Stöhr","doi":"10.2174/0113892002301026240318060307","DOIUrl":"10.2174/0113892002301026240318060307","url":null,"abstract":"<p><strong>Background: </strong>Remimazolam (RMZ) is a novel ultrashort-acting benzodiazepine used for sedation by intravenous administration. The pharmacophore of RMZ includes a carboxyl ester group sensitive to esterase- mediated hydrolysis, which is the primary path of metabolic elimination. However, for the sake of drug safety, a deeper and broader knowledge of the involved metabolic pathways and the evolving metabolites is required. Information is needed on both humans and experimental animals to evaluate the possibility that humans form harmful metabolites not encountered in animal toxicity studies.</p><p><strong>Objective: </strong>The current study aimed at identifying the mechanisms of remimazolam's metabolism and any potential clinically significant metabolites.</p><p><strong>Methods: </strong>Using tissue homogenates from various animals and humans, the liver was identified as the tissue primarily responsible for the elimination of RMZ. CNS7054, the hydrolysis product of remimazolam, was identified as the only clinically relevant metabolite. Using bacterial or eukaryotic over-expression systems, carboxylesterase 1 (CES1) was identified as the iso-enzyme predominantly involved in RMZ metabolism, with no role for carboxylesterase 2. Using a variety of inhibitors of other esterases, the contribution to elimination mediated by esterases other than CES1 was excluded.</p><p><strong>Results: </strong>Besides tissue carboxylesterases, rodents expressed an RMZ esterase in plasma, which was not present in this compartment in other laboratory animals and humans, hampering direct comparisons. Other pathways of metabolic elimination, such as oxidation and glucuronidation, also occurred, but their contribution to overall elimination was minimal.</p><p><strong>Conclusion: </strong>Besides the pharmacologically non-active metabolite CNS7054, no other clinically significant metabolite of remimazolam could be identified.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206418","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":"Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment.","authors":"Asad Ahmad, Juber Akhtar, Mohammad Ahmad, Anas Islam, Badruddeen, Mohammad Irfan Khan, Shaiber Siddiqui, Akash Srivastava","doi":"10.2174/0113892002312605240508042634","DOIUrl":"10.2174/0113892002312605240508042634","url":null,"abstract":"<p><p>Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of <i>Curcuma longa</i>, 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.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955924","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 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, Wen Liu","doi":"10.2174/0113892002299899240515092703","DOIUrl":"10.2174/0113892002299899240515092703","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079754","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":"Inhibition of <i>Glycyrrhiza</i> Polysaccharide on Human Cytochrome P450 46A1 <i>in vitro</i> and <i>in vivo</i>: 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, Jingjing Wu","doi":"10.2174/0113892002305873240520072802","DOIUrl":"10.2174/0113892002305873240520072802","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Materials and methods: </strong>The effects of glycyrrhiza polysaccharide (GP) on the activity of CYP46A1 were investigated <i>in vivo</i> and <i>in vitro</i>. Moreover, the potential regulatory effects of GP on the expressions of CYP46A1, HMG-CoA reductase (HMGCR), and NMDAR were also detected.</p><p><strong>Results: </strong>The <i>in vitro</i> 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 <i>in vivo</i> 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.</p><p><strong>Conclusion: </strong>GP exhibits a significant inhibitory effect on CYP46A1 activity <i>in vitro</i> and <i>in vivo</i>, 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.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154778","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}