Emerging Microbes & Infections
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2026
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IF 7
Xiaoying Wu,Zhanzhe Ge,Haojie Zhan,Mengxiang Zheng,Yiming Feng,Yajun Zhai,Li Yuan,Jianhua Liu,Yushan Pan,Gongzheng Hu,Xiaoyuan Ma,Dandan He
The emergence of multidrug-resistant Klebsiella pneumoniae poses a significant challenge to clinical treatment and public health. Strategies combining antibiotics with FDA-approved non-antibiotic drugs have recently attracted attention as a promising approach to overcome antibiotic resistance. In this study, we systematically evaluated the synergistic effect of the antihistamine loratadine in combination with colistin against K. pneumoniae. Our results demonstrate that loratadine significantly restores the bactericidal activity of colistin against colistin-resistant K. pneumoniae both in vitro and in vivo, without increasing toxicity, while also delaying the development of colistin resistance. Mechanistic investigations using fluorescence-based assays and proteomic analysis revealed that loratadine acts as a potent adjuvant for colistin, effectively restoring its activity against colistin-resistant K. pneumoniae by interfering with lipid A modification. This phenomenon is further supported by the downregulation of lipid A-modifying enzyme-related protein EptB. In addition, the combination of loratadine and colistin disrupts the double-layer membrane barrier, leading to proton motive force (PMF) dysregulation, reduced intracellular ATP levels, and impaired efflux pump activity. Collectively, this study highlights the potential of drug repurposing as an effective strategy to combat antimicrobial resistance and provides a foundation for the development of combination therapies against multidrug-resistant pathogens.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
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2022
·Vol. 74
·期 9
·1241-1250
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IF 4.81
Huang Wenwen,Zhou Xiaoying
ObjectivesTo examine the possible anti-histamine effects of dipotassium glycyrrhizinate (DG), a dipotassium salt of glycyrrhizic acid, on histamine-mediated lung fibroblast activation, differentiation and proliferation; to investigate the potential and underlying mechanisms for pulmonary fibrosis (PF) treatment.MethodsRat primary lung fibroblasts were extracted to establish cell models; histamine, DG and loratadine (LTD, a histamine receptor antagonist) were applied. Cell proliferation, migration and cell cycle were explored; intracellular signal proteins were detected; mitochondrial membrane potential was examined.Key findingsThe anti-histamine effects of DG were found in a similar pattern of LTD on lung fibroblasts. DG inhibited histamine-induced cell activation, proliferation and migration; DG altered histamine-mediated mitochondrial membrane potentials. DG reduced the histamine-induced PAR-2 (a tryptase receptor) expression to impair mast cell tryptase co-working. Histamine-induced expressions of MMP-2, FAK, TNF-α, P38, iNOS were decreased by DG, while Bax and caspase-3, P53 were increased by DG against histamine effects. Histamine drove cells from G0/G1 to S phases, whereas DG rested cells by inhibiting G0/G1 and G2/M phases.ConclusionsThis study provided the evidences that DG can inhibit histamine-induced effects on lung fibroblasts and promote apoptosis of abnormally activated lung fibroblasts, implicating its potential therapeutic mechanisms against PF development, also for those histamine-related diseases.
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XENOBIOTICA
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2021
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IF 1.908
Xian-Mei Song,Bing-Jie Li,Yan-Yan Zhang,Wen-Jing Ge,She-Feng Zhang,Wei-Feng Cui,Geng-Sheng Li,Rui-Feng Liang
Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.
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XENOBIOTICA
·
2021
·
IF 1.908
Jadera Talap,Zhuowei Shen,Jing Nie,Jie Pan,Mingcheng Xu,Kui Zeng,Kaifeng He,Fengting Ou,Houhong He,Jianbiao Yao,Ruwei Wang,Lushan Yu,Su Zeng
6-Hydroxykynurenic acid (6-HKA) is a nitrogen-containing phenolic acid compound in Ginkgo biloba leaves. The pharmacological activities of 6-HKA have been reported and shown that 6-HKA has the potential to become a therapeutic drug and may play an important role in the treatment of nervous system diseases. However, there are few studies on the drug metabolism and transport of 6-HKA. The aim of this study is to investigate the in vitro metabolism of 6-HKA and its interaction with multiple important drug transporters.The in vitro metabolism experiments in the present study demonstrate that 6-HKA might not undergo phase-I or phase-II metabolism in hepatic microsomes/S9 of rats. In addition, some drug transporters, including OAT1/3, OCT2, MDR1, OATP1B1, MATE1/2K and OCTN2, were investigated. The cellular uptake assays indicate that 6-HKA exhibits inhibition to the transport of classical substrates mediated by OAT3, OCT2, MATE2K and OCTN2 but has no significant effect on the transport of substrates mediated by MDR1, OAT1, OATP1B1 or MATE1. Further investigation of cellular accumulation assays shows that 6-HKA might be the substrate of OAT3, but not OCT2 or OCTN2. The bidirectional transport study suggests that 6-HKA is not a substrate of MDR1.The information about the in vitro metabolism of 6-HKA and the interaction between 6-HKA and some transporters will help us to better understand the pharmacokinetic properties of 6-HKA and provide reference for its pharmacodynamics, DDIs and drug-food interactions studies.
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PHARMAZIE
·
2020
·Vol. 75
·期 9
·424-429
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IF 1.198
Chen Jiangfei,Guo Suhang,Yu Xianzhu,Lei Jinxiu,Xu Tao,Zhu Suyan,Chen Lu,Xu Ping,Zhou Xuan,Yu Lushan
Flumatinib, indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, is a structural analog of imatinib and has shown higher potency than imatinib as a BCR-ABL inhibitor. In this paper, the metabolic profile of flumatinib was studied. It was found that
CYP3A4 and CYP2C8 were the main cytochrome P450 enzyme substyles catalyzing the metabolism of flumatinib, and CYP3A4 has a stronger metabolic ability for flumatinib than CYP2C8. Erythromycin, cyclosporine, and voriconazole can inhibit the metabolism of flumatinib in vitro. Accordingly,
co-administration of erythromycin and cyclosporine with flumatinib increased the plasma concentration and the systemic exposure of flumatinib in rats, which indicated that lower doses should be considered in clinical practice.
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Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
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2019
·Vol. 29
·期 1
·46-53
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IF 1.754
Peng Wei,Han Ping,Yu Luyao,Chen Ying,Ye Bingzhu,Qin Luping,Xin Hailiang,Han Ting
The fruits of Xanthium strumarium L., Asteraceae, have been used for various diseases in Chinese folk medicine, including allergic rhinitis, tympanitis, arthritis, ozena etc. The current study was aimed to investigate the therapeutic effects of caffeoylquinic acids from fruits of X. strumarium on allergic rhinitis in animals. The toxicity test indicated that the caffeoylquinic acids have no obvious toxicity. By using HPLC assays combined with reference standards, ten caffeoylquinic acids were identified as the predominant constituents. Anti-allergic activities of the caffeoylquinic acids were evaluated using passive cutaneous anaphylaxis test and Schultz-Dale test; dimethylbenzene induced ear edema test was performed to evaluate its anti-inflammatory effect. Then, the allergic rhinitis model in rats was established to evaluate the therapeutic effects of the caffeoylquinic acids against allergic rhinitis with the following indexes: allergic rhinitis symptom scores, serum levels of pro-inflammatory cytokines, histopathological examination, and histamine release. Our study revealed that the caffeoylquinic acids showed obvious anti-allergic and anti-inflammatory properties, and its treatments were beneficial for ameliorating the nasal symptoms, decreasing pro-inflammatory cytokines, and inhibiting the releases of histamine. Collectively, the caffeoylquinic acids might be utilized as effective and safe disease therapeutic agents for allergic rhinitis.
研究领域:
药理学
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免疫学
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过敏
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植物化学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
·
IF 3.4
Jieping Zhao,Xiu Chen,Hengbin Zhang,Xiaoyan Liu,Yiwen Ma,Jianbiao Yao,Huidi Jiang,Hui Zhou
Shexiang Tongxin Dropping Pill (STDP) is a well-known compound preparation used in traditional Chinese medicine for treating cardiovascular diseases. Bufadienolides are the major active compounds of toad venom and are the key to the seven medicinal herbs that comprise STDP. In this study, a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative determination of nine bufadienolides (bufalin, gamabufotalin, resibufogenin , marinobufagin , arenobufagin, desacetylcinobufagin, telocinobufagin, hellebrigenin, and hellebrigenol) in rat plasma and tissues (heart and liver). The chromatography column used was a Waters ACQUITY UPLC HSS-T3 column with gradient elution using mobile phase consisting of acetonitrile–water (0.1% formic acid added) at a flow rate of 0.25 mL/min. This method passed the methodological validation of plasma and tissues and was successfully applied to pharmacokinetic and tissue distribution studies after oral administration of STDP in healthy and ischemia-reperfusion (I/R) rats. This indicated that most bufadienolides were well absorbed and quickly distributed in the heart and liver. The area-under-the-curve (AUC) (0−t) of most analytes increased in a dose-dependent manner. Moreover, most of the tested components showed lower plasma and higher tissue concentrations in I/R rats than in healthy rats. The above results on the oral pharmacokinetics and tissue distribution may be helpful for the clinical application of STDP.
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Scientific Reports
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2023
·Vol. 13
·期 1
·1-13
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IF 4.6
Xu Rui-Qi,Ma Ling,Chen Timson,Zhang Wei-Xiong,Chang Kuan,Wang Jing
Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical and cosmetic field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this article, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL can remit the histamine-induced scratching behaviors of mice. Second, SL can suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1, 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα can be inhibted by SL, suggesting that SL may impede the PLC/IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx can also be inhibited by SL. The immunofluorescence and molecular docking analysis indicated that SL acts as an inhibitor of transient receptor potential vanilloid-1 (TRPV1) activation to decrease calcium influx against stimuli. In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL can be a useful treatment for histamine-dependent itch.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Xiuyan He,Wenji Hu,Yao Zu
The widespread presence of antihistamines such as loratadine in aquatic environments poses emerging ecotoxicological concerns, yet their developmental impacts remain poorly characterized. In this study, zebrafish embryos were exposed to loratadine (35–350 μg/L) to evaluate its developmental effects. By 2–3 days post-fertilization (dpf), exposed larvae exhibited marked cardiac defects, including pericardial edema, reduced heart rate and cardiac output, and fractional area change ( p < 0.05). By 4–6 dpf, a complete failure of swim bladder inflation was observed in the exposed group, confirmed by histological analysis showing significantly reduced bladder area ( p < 0.0001). Behavioral assays revealed impaired locomotion, with decreased total distance and swimming speed ( p < 0.001). Molecular analyses showed that loratadine significantly altered the expression of cardiac genes ( acta1b , atp2a2a , gata4 , hand2 , tbx5a ) and suppressed key regulators of swim bladder development ( fgf10a , smo , gli2a , fzd2 , fzd5 , wnt2bb ) ( p < 0.05), ultimately resulting in abnormal cardiac and swim bladder development. These findings highlight the pronounced ecotoxicological impact of loratadine on aquatic vertebrates and reinforce the urgent need for improved environmental surveillance and wastewater remediation strategies to curb pharmaceutical contamination in freshwater ecosystems.
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TOXICOLOGY IN VITRO
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2025
·
IF 2.7
Xiu Chen,Xiaoyi Pan,Jieping Zhao,Huihui Jin,Hengbin Zhang,Yongbiao Song,Hui Zhou,Jianbiao Yao,Huidi Jiang
Neocryptotanshinone (NCTS), an ingredient of Salviae Miltiorrhizae Radix et Rhizoma, is a promising compound for development since it exhibits various pharmacological effects including hypoglycemic and anti-inflammatory activities. In this study, we aimed to elucidate the interactions between NCTS and cytochrome P450s (CYPs), including the CYP-mediated NCTS metabolism and NCTS-induced CYP regulation. The results revealed that NCTS was mainly metabolized by CYPs in human liver microsomes (HLMs), and CYP2C8 and 2C9 were identified as the main CYPs involved; the relative contributions of CYP2C8 and 2C9 were 35 % and 65 %, respectively, after normalization of individual CYP abundance in the human liver. Meanwhile, NCTS weakly inhibited CYP1A2, 2C8, and 2C9, with IC 50 > 30 μM. In addition, NCTS induced CYP2B6 and CYP3A4 expression in human primary hepatocytes, and the underlying mechanism was found by the activation of the pregnane X receptor (PXR) vis reporter gene assay. Molecular docking of NCTS and CYPs, PXR confirmed these results. Our study sheds light on the interactions of NCTS with CYPs and provides useful information for predicting potential drug-drug interactions for NCTS, which will be helpful for NCTS development and clinical utilization of drugs containing NCTS.
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