XENOBIOTICA
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2026
·
IF 1.5
Jia-ou Chen,Ling-li Zhou,Jian-heng Lin,Hao-tian Zhou,Lai-fang Sun,Cheng-ke Huang
1. This study aims to investigate the effects of orally administered paeoniflorin (PF), a major bioactive compound from Paeonia lactiflora, on cytochrome P450 (CYP450) enzyme activity in rats to assess potential drug-drug interactions (DDIs). Following PF treatment, rats received a mixed probe drug solution containing phenacetin (PHE), tolbutamide (TOL), omeprazole, and metoprolol, and plasma concentrations of the substrates and metabolites were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. The metabolic ratio, calculated as the ratio of metabolite to parent drug area under the curve (AUC), was used to evaluate CYP activity.2. Results showed that AUCAcetaminophen/AUCPHE values were significantly elevated in PF-treated groups, indicating induction of CYP1A2, whereas AUCOHTOL/AUCTOL values were significantly reduced, suggesting inhibition of CYP2C11. No significant effects were observed on CYP2C or CYP2D2 activities.3. These findings indicate that PF can modulate CYP1A2 and CYP2C11 activities under the experimental conditions tested, as assessed using PHE and TOL as functional markers. However, the magnitude of these effects was modest and observed only at relatively high PF doses (50 and 100 mg/kg). Given the inherent species differences between rat and human CYP enzymes, direct extrapolation of these findings to human CYP1A2 and CYP2C11 requires further validation in human-relevant models.
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RSC Advances
·
2026
·Vol. 16
·期 14
·12570-12578
·
IF 6.1
Hang Yin,Lei Zhu,Xiaoyu Wang,Zhen Wang,Hecheng Wang,Yong Liu
As a natural plant active ingredient, sesamin has the following nutritional values: anti-inflammatory, antioxidant, anti-hypertension, liver protection, and cholesterol reduction, and has been developed for dietary supplements to assist clinical drug therapy. However, it is not known whether it inhibits the catalytic activities of drug-metabolizing enzymes. Hence, the objective of this research was to assess the inhibitory effects of sesamin on cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) and to predict the risk of inducing food–drug interactions (FDIs). The results indicated that sesamin had no significant inhibitory effects on UGTs. However, since people may take sesame in excessive amounts, the FDIs mediated by UGTs still cannot be ignored. Sesamin could increase the potential risk of FDIs by inhibiting the activities of CYP2C9 and CYP2C19. It is worth noting that for phenytoin, a CYP2C9 substrate with a narrow therapeutic window, sesamin can significantly inhibit the formation of its hydroxylation products and cause clinically significant FDIs. Therefore, when patients are being treated with CYP2C9 and CYP2C19 substrate drugs with narrow therapeutic windows, high doses of sesame or other sesamin-rich substances should be avoided.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Xin Gao,Zouhua Xu,Qingxie Liu,Chenchen Yuan,Xiaowu Dong,Xiaolei Shi,Qingtian Zhu,Keyan Wu,Hongwei Xu,Jiajia Pan,Guotao Lu,Weiming Xiao,Shengfeng Wang,Yaodong Wang
Introduction: Proton pump inhibitors (PPIs) are widely prescribed for gastrointestinal disorders and are often used empirically in patients with pancreatic disease, yet their long-term impact on pancreatic health remains unclear. We evaluated whether regular PPI use is associated with risks of acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC).Methods: We analyzed 489,394 UK Biobank participants aged 38–73 years, comparing regular PPI users with non-users and with histamine-2 receptor antagonist (H2RA) users as an active comparator. Associations with incident pancreatic outcomes were estimated using Cox regression models, landmark analysis, and propensity score matching, supplemented by multiple sensitivity analyses, including stratified/interaction analyses, E-values, time-varying exposure models with immortal-time correction, dfbeta residuals correction, stricter follow-up with Firth penalization, full-cohort multivariable modeling, and alternative matching (disease risk score 1:1, entropy balancing). Complementary in vivo experiments used a cerulein-induced acute pancreatitis mouse model to examine the effects of short- and long-term PPI administration on pancreatic inflammation and histopathology.Results: In primary analyses, regular PPI use showed a time-dependent association with acute pancreatitis. However, this association was not robust: multiple sensitivity analyses indicated instability of the finding. Experimental validation in mice demonstrated that neither short-term nor long-term PPI administration altered pancreatic inflammation or histopathological damage in the cerulein-induced model.Discussion: Integrating large-scale cohort data with experimental evidence, our findings suggest that regular PPI use does not meaningfully influence the risk of acute pancreatitis, chronic pancreatitis, or pancreatic cancer.
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FITOTERAPIA
·
2026
·
IF 2.6
Xiaojing Wei,Binjing Zhao,Xinyi Jiang,Lunli Lan,Rui Wang,Yuanyuan Li
Vladimiria souliei(Franch.)Ling is used as medicine with dried roots, which is a perennial herb in Asteraceae family. It has been generally applied as traditional Chinese medicine with relieving abdominal swelling or pain, and treatment of digestive system disease. However, the pharmacological mechanism of alleviating gastric ulcer (GU) for this herb were still unknown. UPLC-Q-TOF/MS was performed to analyze the main components of Vladimiria souliei extract (VSE). Based on the results of histopathological observation, cytokines assay, and immunohistochemistry staining, the therapeutic effect of VSE on ethanol-induced GU was appraised. Meanwhile, the CCK-8, LDH assay and crystal violet staining were assessed to evaluate the appropriate concentration of VSE in vitro. In GES-1 cells induced by ethanol, the cell viability, ROS and cell membrane damage assay were detected after the interference of VSE. Then, several pivotal proteins relating to necroptosis in GES-1 were evaluated through immunofluorescence staining to illustrate the further pharma-cological mechanisms. As a result, VSE significantly restrained the expansion of ulcer area, reduced the pepsin activity, restored the levels of SOD, decreased the levels of MDA, ROS, TNF-α, IL-1β, IL-6, and IL-18, ultimately ameliorated the gastric mucosa injury. Further analysis exhibited that VSE significantly inhibited the cellular necroptosis by down-regulating the levels of RIP1, RIP3 and MLKL. Conclusions: This research clarified that the VSE could improve gastric mucosal injury through inhibition of RIP1-RIP3-MLKL necrosome activation, which might provide scientific evidences on the application of Vladimiria souliei as a ethnic herb to ameliorate GU.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Jiang-Hong Luo,Wan-Shuang Zou,Jing Li,Wei Liu,Jing Huang,Hu-Wei Wu,Jian-Lin Shen,Fei Li,Jia-Shuang-Wei Yuan,An-Kang Tao,Liang Gong,Jun Zhang,Xiao-Yin Wang
This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.
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International Journal of Electrochemical Science
·
2023
·
IF 1.5
Yanxia Liu,Wei Du,Xiuquan Yao,Chunlin Liu,Xiaofang Luo,Lei Guo,Chao Guo
The corrosion inhibition performance of Omeprazole (OMP) on X60 steel in 0.5M H 2 SO 4 solution was studied by electrochemical impedance spectroscopy and electrochemical polarization curves. These tests are complemented by theoretical calculations using molecular dynamics. The corrosion inhibition efficiency increases with the concentration of OMP, a hybrid corrosion inhibitor that adsorbs on X60 steel following the Langmuir adsorption isotherm. The adsorption configuration calculated by molecular dynamics showed that the OMP molecules were arranged in parallel on the surface of X60 steel, which ensured its excellent inhibition performance.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Renhao Ni,Yang Luo,Lingjing Jiang,Xufeng Mao,Yuyao Feng,Subinuer Tuersun,Zeming Hu,Yabin Zhu
The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.
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ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jieqing Feng,Qisheng Zhong,Ting Zhou
The online coupling technique of sample preparation with chromatography is a frontier topic in analytical chemistry since it minimizes errors caused by sample loss, shortens analysis time, and reduces solvent consumption. An online pressure change focusing-supercritical fluid selective extraction chromatography (PCF-SFSEC) technique was developed in this study, realizing extraction, purification, separation, and detection in a single run with only microliter-scale samples. The pressure change focusing strategy achieved column-head stacking by decreasing the dissolving capacity of the supercritical fluid, enabling the large volume introduction of extractants into supercritical fluid chromatography without causing peak broadening or distortion. All the extracts could be directly loaded into the chromatography system without split flow. Based on the supercritical fluid selective extraction (SFSE) strategy, the sorbents removed interferences and water from samples, effectively alleviating matrix effects and realizing the direct aqueous sample analysis. The efficiency of online PCF-SFSEC was demonstrated by the enantioselective analysis of 22 chiral drugs in rat plasma, covering eight categories with different pharmacological effects. The entire analysis took 25 min, consuming only 5 μL samples. All analytes in PCF-SFSEC obtained sharp and symmetrical peaks with resolutions higher than 1.0, and 86% had resolutions higher than 1.5. Limits of quantification (LOQs) ranged from 0.0600 to 32.1 μg/L. Recoveries were in the range of 75.8–117.2%. In addition, the developed approach obtained more satisfactory repeatability and significantly reduced matrix effects than conventional methods. The newly established online PCF-SFSEC technique is believed to be a green and powerful tool for the chiral analysis of complex samples.
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TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Shiqi Duan,Yan Jia,Zhihang Zhu,Lancheng Wang,Peng Xu,Youmei Wang,Bin Di,Chi Hu
Information regarding the metabolism of illicit drugs is under urgent need for toxicological assessment . Its development, however, is limited by the currently available animal models. To this end, we proposed three-dimensional (3D) HepaRG spheroids as an in vitro model to study the effects of illicit drugs on hepatic cytochrome P450 (CYP450) enzymes and potential drug-drug interactions (DDIs). By comparing the results from animal and cell experiments, we confirmed the significant impact of heroin, morphine, tetrahydrocannabinol , and fentanyl on CYP450 enzymes, and the 3D spheroids results were in good agreement with the animal results for 2B6, 2C19, 2D6. Using 3D HepaRG spheroids, we demonstrated DDIs between heroin as a 2B6 perpetrator and clinical medicine for cancer, depression, and illicit drug withdrawal. Specifically, the clearance rate of 5.4 μM bupropion was increased by 214 % under DDI with 5 µM heroin, highlighting the importance of DDI pre-screening and individualized medication guidance for illicit drug users. This research contributes to the growing body of evidence regarding the metabolic toxicity of illicit drugs and suggests 3D HepaRG spheroids as a high-throughput and cost-efficient platform for DDI analysis.
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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Shasha Liu,Ruohan Cheng,Hui He,Kunming Ding,Rongmi Zhang,Yuanyuan Chai,Qinwei Yu,Xin Huang,Luyong Zhang,Zhenzhou Jiang
This study aimed to investigate the effect and mechanism of 8-methoxypsoralen (8-MOP) on acetaminophen (APAP)-induced hepatotoxicity in mice. The study found that 1 h after intraperitoneal injection of 300 mg/kg APAP, treatment with 40 mg/kg, 80 mg/kg and 120 mg/kg 8-MOP could reduce serum transaminase level and histopathological liver necrosis area. Elevated mRNA expression of liver inflammatory mediators caused by excessive APAP was also reversed. 8-MOP significantly reduced APAP-induced hepatotoxicity dose-dependently, and the highest therapeutic dose of 8-MOP (120 mg/kg) had no harmful effects on the liver. Cocktail probe assay revealed that 8-MOP can inhibit Cyp2e1 enzymatic activities of mice, thereby reducing the production of acetaminophen-cysteine (APAP-CYS), a toxic metabolite of APAP. 8-MOP had no significant effect on the protein and gene expression of Cyp2e1. The three-dimensional structures of mouse Cyp2e1 were constructed by homologous modeling. Molecular docking showed that 8-MOP had a good binding effect on the enzyme activity site of Cyp2e1. In summary, 8-MOP dose-dependently attenuated APAP-induced hepatotoxicity by binding to Cyp2e1 and occupying the active center of the enzyme, thus competitively inhibiting the oxidative metabolism of APAP, and reducing the generation of toxic product APAP-CYS.
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Biomedicines
·
2021
·Vol. 9
·期 10
·1320
·
IF 6.081
Xiaoke Zheng,Hanyu Yang,Lan Qin,Siqian Wang,Lei Xie,Lu Yang,Weimin Kong,Liang Zhu,Li Liu,Xiaodong Liu
Liver failure is associated with increased levels of brain aromatic amino acids (AAAs), whose transport across the blood–brain barrier (BBB) is mainly mediated by L-amino acid transporter 1 (LAT1). We aimed to investigate whether liver failure induced by bile duct ligation (BDL) increases levels of brain AAAs by affecting the expression and function of LAT1. The LAT1 function was assessed using the brain distribution of gabapentin. It was found that BDL significantly increased levels of gabapentin, phenylalanine, and tryptophan in the cortex, hippocampus, and striatum of rats, and upregulated the expression of total LAT1 protein in hippocampus and striatum as well as cortex membrane LAT1 protein. HCMEC/D3 served as in vitro BBB model, and the data showed that both the serum of BDL rats and bilirubin induced LAT1 expression and function, while bilirubin oxidase almost abolished the upregulation of LAT1 protein by bilirubin and the serum of BDL rats. The enhanced function and expression of LAT1 were also observed in the hippocampus and striatum of hyperbilirubinemia rats. Both aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone and AhR silencing obviously attenuated the upregulation of LAT1 protein by bilirubin or omeprazole. This study provides the first evidence that BDL upregulates LAT1 at the rat BBB, attributed to the activation of AhR by the increased plasma bilirubin. The results highlight the mechanisms causing BDL-increased levels of brain AAAs and their physiological significance.Keywords:L-amino acid transporter;blood–brain barrier;liver failure;unconjugated bilirubin;aryl hydrocarbon receptor
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Journal of Analytical Science and Technology
·
2021
·Vol. 12
·期 1
·1-9
·
IF 2.769
Liu Mingyang,Du Xuejun,Xu Ke,Yan Binwei,Fan Zaibi,Gao Zideng,Ren Xueqin
Berberine hydrochloride (BH) is an isoquinoline alkaloid normally used as drug to treat diseases. Compared with the traditional detection methods, the carbon quantum dots (CQDs) have better selectivity, high sensitivity, easy operation, and is inexpensive which could be widely utilized as fluorescent nanoprobes to detect various compounds quantificationally. And ratiometric fluorescent sensors conspicuously increase sensitivity and precision detection and improve quantification. In this work, we use water-soluble and fluorescent cationic carbon dots cetylpyridinium chloride monohydrate (CPC)-CQDs to connect with pinacyanol chloride (PC) and sodium tetraphenylborate (ST) as the ratiometric fluorescent probe to detect BH. The ratiometric fluorescent probe has high sensitivity towards alkaloids and metal ions, photochemical stability (60 min), and pH stability (from 6.0 to 8.0), with the detection range from 0 to 200 μM, and limit was as low as 57.35 nM. The accuracy of the method was verified by spiked recovery experiment in different human blood serums which were drawn from healthy adult volunteers to explore the practicability. The recoveries were in the range 94.34 to 105.48% with relative standard deviations (RSD) of 0.80 to 2.92%. In addition, we could observe that the fluorescence was gradually darkened, and the color turned yellow to realize the visual detection. It is expected that this work would open up a new strategy for detecting BH in the environment and human blood serums.
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