Frontiers in Pharmacology
·
2023
·
IF 5.6
Xun Tianrong,Rong Yan,Lv Bin,Tian Jinfei,Zhang Qing,Yang Xixiao
Purpose: Voriconazole (VOR) is combined with atorvastatin (ATO) to treat fungal infections in patients with dyslipidemia in clinical practice. However, the pharmacokinetic interactions and potential mechanisms between them are unknown. Therefore, this study aimed to investigate the pharmacokinetic interactions and potential mechanisms between ATO and VOR.Patients and methods: We collected plasma samples from three patients using ATO and VOR. Rats were administered either VOR or normal saline for 6 days, followed by a single dose of 2 mg/kg ATO, and then plasma samples were collected at different time points. The incubation models of human liver microsomes or HepG2 cells were constructed in vitro. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system was developed to determine the concentration of ATO, 2-hydroxy-ATO, 4-hydroxy-ATO, and VOR.Results: In patients, VOR significantly reduced the metabolism of ATO and slowed the formation of 2-hydroxy- and 4-hydroxy-ATO. In rats pretreated with orally administered VOR for 6 days or normal saline given a single dose of 2 mg/kg ATO administered orally on Day 6, the t1/2 of ATO was significantly prolonged from 3.61 to 6.43 h, and the area under the concentration-time curve (AUC0–24h) values of ATO increased from 53.86 to 176.84 h μg.L−1. However, the pharmacokinetic parameters of VOR (20 mg/kg) with or without pretreatment with ATO (2 mg/kg) only slightly changed. In vitro studies indicated that VOR inhibited the metabolism of ATO and testosterone, and the IC50 values were 45.94 and 49.81 μM. However, no significant change in transporter behaviors of ATO was observed when VOR or transporter inhibitors were co-administered.Conclusion: Our study demonstrated that VOR has significant interactions with ATO, probably due to VOR’s inhibition of the CYP3A4-mediated metabolism of ATO. Based on the clinical cases and potential interactions, the basic data obtained in our study are expected to help adjust the dose of ATO and promote the design of rational dosage regimens for pharmacotherapy for fungal infections in patients with dyslipidemia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·
IF 4.259
Yuhong Liu,Jiali Liang,Jiazhen Wu,Hanbin Chen,Zhenbiao Zhang,Hongmei Yang,Liping Chen,Haiming Chen,Ziren Su,Yucui Li
Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yukun Lin,Kunjing Liu,Jiahui Chen,Tingjie Li,Zijin Sun,Yifan Fan,Peng Zou,Yanting Liu,Chunyu Wang,Chongyang Ma,Xueqian Wang,Fang Lu,Fafeng Cheng,Changming Zhai
A B S T R A C T Ethnopharmacological relevance Pinellia ternata (Ban-xia) and Coptidis Rhizoma (Huang-lian) form a classic herb pair (BXHL) in traditional Chinese medicine that has demonstrated clinical efficacy against Helicobacter pylori ( H. pylori ) infection. However, its pharmacological mechanisms remain insufficiently defined. Aim of the study This study aimed to (1) evaluate the anti- H. pylori colonization effects of BXHL in vitro and in vivo; (2) elucidate its mechanism through the NLRP3-mediated pyroptosis pathway; and (3) assess its influence on gastrointestinal microbiota and identify potential active components. Materials and methods BXHL composition was characterized by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Anti- H. pylori activity was examined using GES-1 cell co-culture and infected mouse models. Gene expression and signaling pathways were analyzed by RNA-seq, ELISA, RT-qPCR, Western blotting and IHC. Histopathology, bacterial load assays, and ultrastructural observation assessed anti-colonization efficacy. Microbiota alterations were analyzed via 16S rRNA sequencing and molecular docking evaluated interactions between BXHL compounds and NLRP3 targets. Results BXHL significantly reduced H. pylori adhesion, colonization and restored NLRP3-mediated pyroptosis suppressed by infection. Transcriptomic and molecular analyses confirmed reactivation of the NLRP3 signaling cascade. BXHL preserved gut microbial diversity, unlike triple therapy, and exhibited moderate direct antibacterial effects. Conclusion BXHL inhibits H. pylori colonization through suppressing bacterial adhesion factors and activating NLRP3-mediated pyroptosis, while causing no disruption to the gut microbiota. These findings position BXHL as a safe and effective adjunctive therapy, which provides a novel strategy to improve H. pylori eradication that complements conventional antibiotics.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）