Article
Toxicology
Che -Fu Chang, Yu-Ching Chang, Jing-Tang Lin, Chen-Wei Yu, Yu-Ting Kao
Summary: UGTs in the gastrointestinal tract play a crucial role in protecting the body against toxic xenobiotics. This study examined the metabolism of raloxifene in differentiated Caco-2 monolayers by inducing the expression of UGT1A8 and UGT1A10 in these cells. The results suggest that salvigenin may enhance the pharmacological effects of UGT substrate drugs.
TOXICOLOGY IN VITRO
(2021)
Article
Biochemistry & Molecular Biology
Jiri Vrba, Barbora Papouskova, Katerina Lnenickova, Pavel Kosina, Vladimir Kren, Jitka Ulrichova
Summary: 2,3-Dehydrosilybin A and B are preferentially metabolized through conjugation reactions, with several human UGT and SULT enzymes potentially playing a role in these conjugations.
Article
Engineering, Chemical
Mingyue Zhu, Zhenhao Tian, Lingling Jin, Xiaokui Huo, Chao Wang, Jingnan Cui, Yan Tian, Xiangge Tian, Lei Feng
Summary: A novel fluorescent probe BDMP with high sensitivity for detecting UGT1A8 was developed, showing a good linear relationship with UGT1A8 concentration. BDMP successfully imaged endogenous UGT1A8 in human cancer cell lines and could also visualize UGT1A8 in tumor tissues. This suggests that BDMP is a promising molecular tool for investigating UGT1A8-mediated physiological function in humans.
FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING
(2022)
Article
Cell Biology
Jun Matsumoto, Anzu Nishimoto, Shogo Watari, Hideo Ueki, Shoya Shiromizu, Naohiro Iwata, Tatsuaki Takeda, Soichiro Ushio, Makoto Kajizono, Masachika Fujiyoshi, Toshihiro Koyama, Motoo Araki, Koichiro Wada, Yoshito Zamami, Yasutomo Nasu, Noritaka Ariyoshi
Summary: This study found that the mRNA expression levels of UGT genes are downregulated in renal cell carcinoma (RCC) tissues and that the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are correlated with better cancer-specific survival and overall survival in patients with RCC.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Liangliang He, Chunxia Xu, Ziying Wang, Shuyi Duan, Jinjin Xu, Chuan Li, Xinsheng Yao, Frank J. Gonzalez, Zifei Qin, Zhihong Yao
Summary: The study aimed to identify bioactive compounds from Xian-Ling-Gu-Bao capsule against estrogen glucuronidation. It found potent inhibitors for UGT1A10, 1A1, and 2B7, laying an important foundation for the pharmacodynamic material basis of XLGB. Six compounds demonstrated potent inhibitory effects against these three active enzymes, indicating their potential as natural inhibitors of estrogen glucuronidation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Toxicology
Kouji Tagawa, Yoshihiro Maruo, Yu Mimura, Shinichi Ikushiro
Summary: The adverse effects of irinotecan are associated with genetic variants of UGT1As, which are enzymes that metabolize the drug. UGT1A1 and UGT1A6-UGT1A10 showed SN-38 glucuronidation activity, with UGT1A1 being the most active. Variants of these isoforms resulted in decreased glucuronidation activity. This study provides insights into the relationship between UGT1A variants and the level of glucuronidation, allowing for potential toxicity prediction before irinotecan treatment.
TOXICOLOGY MECHANISMS AND METHODS
(2023)
Article
Biochemistry & Molecular Biology
Sangeeta Shrestha Sharma, Shishir Sharma, Jie Zhao, Matthias Bureik
Summary: Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are important human drug metabolizing enzymes, and this study explores their mutual interactions. The study used recombinant co-expression of 19 human UGTs with CYP enzymes in yeast and found that UGT co-expression had a significant effect on P450 activity in most cases. The study also observed varying degrees of influence of CYP co-expression on UGT activity.
Article
Pharmacology & Pharmacy
Kai Huang, Linling Que, Ying Ding, Nannan Chu, Zhenzhong Qian, Wei Qin, Yuanxing Chen, Jisheng Zhang, Qing He
Summary: This study aimed to determine the kinetics of MHD-O-glucuronide formation in human liver, intestine, and kidney, and identify the primary UGT isoforms involved in the glucuronidation of MHD. The results showed that MHD could be metabolized by UGTs in all three organs, with hepatic glucuronidation being the critical pathway. UGT2B7 and UGT1A9 were identified as the main UGT isoforms mediating the formation of MHD-O-glucuronide in the liver.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Article
Nutrition & Dietetics
Alessandra Nishioka, Eric de Castro Tobaruela, Layanne Nascimento Fraga, Francisco A. Tomas-Barberan, Franco Maria Lajolo, Neuza Mariko Aymoto Hassimotto
Summary: This study identified large interindividual variations in the biological response to citrus flavanones and aimed to understand the main determinants underlying these differences in metabolism and excretion. A new stratification based on metabolic profiles was proposed for volunteers, suggesting a possible relationship between gut microbiota composition, polymorphisms of phase II enzymes, and the interindividual variability of metabolism.
Article
Pharmacology & Pharmacy
Chenghong Zhang, Dian Su, Edna F. Choo, Lichuan Liu, Sudheer Bobba, Jamie D. Jorski, Quynh Ho, Jing Wang, Jane R. Kenny, S. Cyrus Khojasteh, Donglu Zhang
Summary: GDC-0810 is a potential therapeutic agent for breast cancer treatment. In this study, a unique diglucuronide metabolite, M2, was identified in human plasma but absent in rats. Acyl glucuronide M6 and N-glucuronide M4 were also prominent metabolites in human plasma. In vitro experiments revealed that M2 was more efficiently formed from M6 and acyl glucuronidation was mainly catalyzed by UGT1A8/7/1 while N-glucuronidation was mainly catalyzed by UGT1A4. The absence of M2 and M4 in rats was attributed to the low to no expression of UGT1A4 in rodents. The formation of M2 involving both acyl- and N-glucuronidation is a complex mechanism that poses challenges in predicting its formation using human in vitro systems.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Biology
Yifan Tu, Lu Wang, Yi Rong, Vincent Tam, Taijun Yin, Song Gao, Rashim Singh, Ming Hu
Summary: Research has shown that the distribution of orally administered phenolic drugs is mediated by intestinal glucuronidation and hepatic recycling, revealing a new mechanism of distribution called "Hepatoenteric Recycling (HER)."
Article
Environmental Sciences
Anja Stajnko, Agneta Annika Runkel, Tina Kosjek, Janja Snoj Tratnik, Darja Mazej, Ingrid Falnoga, Milena Horvat
Summary: The study found that CYP2C9*2 and *3 SNPs have an impact on the metabolism of DEHP, while CYP2C19*17 and UGT1A7*3 SNPs may serve as potential biomarkers for susceptibility or resilience to exposure to phthalates and DINCH.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Ting Du, Rongjin Sun, Imoh Etim, Zicong Zheng, Dong Liang, Ming Hu, Song Gao
Summary: The study revealed a significant impact of age on the glucuronidation and oral bioavailability of Raloxifene in rats, with slower metabolism and higher oral bioavailability in the duodenum of young rats. The efficiency of enterohepatic recycling was higher at 11 weeks compared to 4 weeks.
PHARMACEUTICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Shoji Nakamura, Ryohei Yamashita, Yuu Miyauchi, Yoshitaka Tanaka, Yuji Ishii
Summary: Adenine-related compounds act as allosteric inhibitors of UDP-glucuronosyltransferase (UGT) in rat and human liver microsomes treated with detergent or pore-forming peptide. In this study, adenine-related compounds were found to inhibit 4-methylumbelliferone (4-MU) glucuronidation in mouse liver microsomes in a non-competitive manner, with AMP counteracting the inhibitory effects of ATP and ADP. Additionally, NAD(+) and NADP(+) were potent inhibitors of 4-MU glucuronidation, while the reduced forms NADH and NADPH did not show inhibitory effects.
Article
Gastroenterology & Hepatology
Thierry Poynard, Olivier Deckmyn, Valentina Peta, Mehdi Sakka, Pascal Lebray, Joseph Moussalli, Raluca Pais, Chantal Housset, Vlad Ratziu, Eric Pasmant, Dominique Thabut
Summary: In middle-aged Europeans, the use of the standard unisex 1 mg/dL cutoff underestimates the prevalence of Gilbert syndrome (GS) in women. The prevalence of illnesses and survival rates differ between GS and hypobilirubinemia compared to normobilirubinemia, with cholelithiasis being significantly higher in men with GS.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)