Animals
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2025
·Vol. 15
·期 5
·661
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IF 2.7
Yuan Feng,Mengyuan Zhang,Wenqing Yuan,Dan Zhao,Zhixuan Luo,Zihui Tang,Yongheng Wang,Ming Cang
Simple SummaryWhen precious species are about to die out or excellent strains need to be preserved, we want to use technology to preserve their gametes so that they can be used directly when needed in the future. The damage caused by vitrification of frozen oocytes needs to be addressed. In this study, the damage to oocytes caused by freezing was minimized by natural chemicals. The results showed that imperatorin reduced the level of oxidative stress and increased mitochondrial activity in mouse oocytes after vitrification freezing. In conclusion, the addition of imperatorin to vitrification freezing solution improved the activity of frozen mouse oocytes and provided new perspectives for the improvement of vitrification freezing technology.Imperatorin (IMP) is a naturally occurring furanocoumarin with beneficial biological activities such as anticancer, antioxidant, and neuromodulatory properties. Currently, the protective effects and mechanisms of IMP on oxidative stress experienced by mouse oocytes after vitrification–thawing remain unclear. To investigate the influence of IMP on mouse oocyte development after vitrification–thawing, we added different concentrations of IMP to the vitrification and thawing media. Results indicated that the addition of 40 μM IMP enhanced post-thaw fertilization capacity, reduced intracellular reactive oxygen species (ROS) levels, and increased intracellular glutathione (GSH) levels. IMP also improved mitochondrial health by alleviating the decrease in mitochondrial membrane potential (MMP) and enhancing mitochondrial distribution. IMP reduced intracellular ROS levels by affecting the transcription of the antioxidant genesSOD2,NRF2, andHO-1and enhancing SOD activity. It also elevated GSH levels viaGPX1, improved mitochondrial function, and decreased early apoptosis throughBcl-2.In conclusion, IMP enhanced ovum health through the alleviation of oxidative stress. The present study provides useful information for further exploration of the molecular mechanisms of IMP in female reproductive cells and offers a novel approach for the improvement of vitrification technology.
研究领域:
生殖生物学
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分子生物学
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生物化学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Cheng Wang,Yajing Hou,Shuai Ge,Jiayu Lu,Xiangjun Wang,Yuexin Lv,Nan Wang,Huaizhen He
Anaphylaxis is a severe systemic allergic reaction that exhibits multiple clinical symptoms. The Mas-related G protein-coupled receptor X2 (MRGPRX2) is recognized as a key cell receptor mediating allergic diseases and drug-induced anaphylactoid reactions. Thus, it has been a promising target for preventing and treating these reactions. Based on the potential activity of imperatorin and active structural feature of MRGPRX2, we first demonstrated that the synthetic imperatorin derivatives (IDs) could significantly inhibit MRGPRX2 agonist-induced degranulation and cytokine release in LAD2 cells, as well as alleviate local and systemic anaphylaxis in mice. The IC 50 value of the most promising compound is an order of magnitude lower than that of imperatorin. IDs were further identified to display anti-pseudo-allergic activity by binding MRGPRX2 with the tertiary nitrogen substructures, just liking the reported MRGPRX2-ligand. These results would propose evidence for discovery of agents for treating MCs-dependent allergic disorders.
研究领域:
免疫学
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药理学
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分子生物学
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PubMed
高影响因子
MAIN GROUP CHEMISTRY
·
2022
·Vol. 21
·期 1
·315-328
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IF 0.641
Jiang Wen,Zhou Xiaohua,Ni Ke
Soxhlet extraction method was used to extract imperatorin from Angelica dahurica, and the extraction ratio under different extraction condition was optimized to attain the best condition. Then, XAD-16 macroporous resin was selected as the optimal resin to boost the extraction ratio of imperatorin. Afterwards, the higher purity of imperatorin (96.84±0.2%) was separated by preparative HPLC system. Next, the photocatalytic reaction between the above imperatorin and collagen which the highest levels in skin was investigated using UV-vis spectroscopy, amino acid analysis and HPLC analysis. The results showed that imperatorin reacted with collagen only under ultraviolet light which caused the denaturation of collagen, and three new products were generated. The ultraviolet products were isolated by preparative HPLC system and separately detected by high-resolution mass spectrum. The possible UV photocatalytic reaction mechanism between imperatorin and collagen is that ultraviolet light induces the increase of the activity of the imperatorin to react with the tyrosine in the collagen, resulted in the denaturation of collagen and reestablish of the normal epidermal tissue in skin.
研究领域:
药理学
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生物化学
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高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·Vol. 75
·期 4
·502-514
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IF 3.3
Zhou Nan,Yong Suyun,Shi Xianpeng,Zhang Peng,Wang Jianhua
ObjectivesReactive oxygen species (ROS) are involved in the structural remodelling of vascular segments and vascular beds. We identified a new imperatorin derivative, OW1, which has significant effects on vasodilation and inhibits vascular remodelling in hypertensive rats. In this study, we investigated whether OW1 inhibits vascular cell proliferation and migration by attenuating Nox1-ROS signalling.MethodsVascular smooth muscle cells (VSMCs) were treated with OW1 (1, 3 and 10 µmol/L) for 24 h incubation, and it has been analysed for proliferation and peroxidation levels. Moreover, the mRNA and protein levels of nicotinamide adenine dinucleotide phosphate oxidase (Noxs) were measured by RT-PCR and western blot. Furthermore, Nox1-ROS-MAPK/MMP mediated cell proliferation was detected by western blot.Key findingsAng II-induced increases in the levels of peroxidation and Noxs in VSMCs were also inhibited by OW1. OW1 attenuates cell proliferation and migration through the MAPK pathway and MMPs. OW1 treatment had no significant effects on cell migration, ROS levels, or the expression of phosphorylated MAPKs in VSMCs when Nox1 was knocked down. OW1 reduced ROS levels and expression of phosphorylated MAPKs in NIH3T3 cells with a Nox1 overexpression plasmid.ConclusionOW1 may inhibit vascular remodelling by downregulating the Nox1-ROS-MAPK/MMP signalling pathway.
研究领域:
药理学
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心血管生物学
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细胞生物学
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分子生物学
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PubMed
高影响因子
ACS Applied Nano Materials
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2024
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IF 5.3
Qiuxiang Li,Guowei Zhao,Fengling Wu,Xilan Tang,Zhenggen Liao,Xinli Liang,Wei Dong
Imperatorin (IMP) has demonstrated potential in reversing drug resistance in various tumor cells; however, its limited clinical application and development are attributed to its poor water solubility and low bioavailability. The current work is intended to enhance the oral bioavailability of IMP and its efficacy in overcoming tamoxifen (TAM) resistance in breast cancer cells. We employed mPEG–PLLA and Cremophor RH60 (RH60) to prepare imperatorin nanomicelles (IMP-RH60/mPEG–PLLA). The freeze-dried powder of IMP-RH60/mPEG–PLLA demonstrated a porous structure, and upon reconstitution, the resulting solution exhibited clarity and transparency. The particle size was measured to be 25.48 ± 0.92 nm, with a zeta potential of −5.50 ± 1.06 mV. The encapsulation efficiency was determined to be 85.78 ± 0.84%, while the drug loading was found to be 2.66 ± 0.03%. In comparison to the active pharmaceutical ingredients (APIs) of IMP, IMP-RH60/mPEG–PLLA exhibited a significant increase in in vitro release, improved bioavailability in rats, and enhanced uptake by MCF-7/TAM cells. The coadministration of IMP-RH60/mPEG–PLLA and TAM effectively inhibited the proliferation, colony formation, migration, and invasion of MCF-7/TAM cells. This outcome could potentially be attributed to the downregulation of GST-π and MDR1 drug resistance genes, consequently augmenting the susceptibility of MCF-7/TAM cells to TAM. An experimental model of BALB/c nude xenograft, consisting of human breast cancer cells resistant to tamoxifen (TAM), was established in order to assess the potential in vivo reversal of TAM resistance through the use of IMP-RH60/mPEG–PLLA. The growth of xenografts was inhibited by IMP-RH60/mPEG–PLLA, and it induced apoptosis in tumor tissues through the downregulation of Ki-67, GST-π, and MDR1 gene expression. The findings indicated that the utilization of IMP-RH60/mPEG–PLLA micelles resulted in an enhancement of IMP’s bioavailability and its efficacy in overcoming TAM resistance.
研究领域:
药学
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肿瘤学
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纳米技术
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药理学
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高影响因子
FASEB JOURNAL
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2026
·Vol. 40
·期 5
·e71641
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IF 4.3
Xiaoxue Wang,Zexin Zhu
Rosacea is a chronic inflammatory dermatological disorder involving the activation of various signaling pathways. Imperatorin (IMP), a coumarin compound, has been documented to exhibit anti‐inflammatory properties. Nevertheless, its therapeutic efficacy in managing rosacea remains unexplored. Bioinformatics and network pharmacology approaches were utilized to elucidate potential signaling pathways and molecular targets of IMP in the context of rosacea. Subsequently, to assess the in vivo therapeutic efficacy of IMP, murine models exhibiting rosacea‐like inflammatory responses were developed. Additionally, in vitro experiments were conducted to elucidate the molecular mechanisms underlying the anti‐rosacea effects of IMP. Our findings demonstrated that both intraperitoneal and topical administration of IMP significantly attenuated skin inflammation in mice with LL37‐induced rosacea models. Mechanistic investigations, guided by bioinformatics and network pharmacology analyses, revealed an interaction between JNK1 and STAT1. IMP was found to directly bind to JNK1 and STAT1, disrupting their interaction, thereby inhibiting STAT1 phosphorylation and nuclear translocation. This inhibition resulted in decreased production of STAT1‐mediated inflammatory mediators in keratinocytes. These results suggest that IMP may serve as a promising therapeutic agent for inflammatory skin diseases by targeting the crosstalk between JNK1 and STAT1. IMP treatment disrupts the interaction between JNK1 and STAT1, thereby attenuating STAT1 activity. This interference subsequently diminishes the phosphorylation and nuclear translocation of STAT1, which ultimately results in a reduced production of inflammatory cytokines and chemokines. Consequently, this process alleviates the symptoms of rosacea.
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高影响因子
Drug Design Development and Therapy
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2025
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IF 5.1
Hualu Wu,Qian Liu,Yuxin Shen,He Qi,Jiade Zhao,Qiaoying Li,Hailun Xia,Ren-Ai Xu,Lu Shi
Purpose The purpose of this study was to establish an in vitro incubation system and an in vivo model to investigate the potential kinetic interactions of macitentan with imperatorin and curcumin, and to validate the potential inhibitory mechanisms using molecular docking.Methods In vitro, the enzyme kinetic profile of macitentan was explored in rat liver microsomes (RLM) and human liver microsomes (HLM). Furthermore, molecular docking technique was used to study the sites of action of macitentan, imperatorin, and curcumin with CYP 3A4. In vivo, the pharmacokinetic parameters of macitentan were investigated in Sprague-Dawley (SD) rats administered the drug orally, both as a single agent and in combination with imperatorin and curcumin.Results In vitro, the results indicated that imperatorin and curcumin could inhibit the metabolism of macitentan, with IC50 values of 6.58 μM and 10.86 μM in RLM and 6.97 μM and 5.71 μM in HLM, respectively. And in the study of inhibition type, in RLM, the inhibition types of imperatorin and curcumin on macitentan were mixed and non-competitive, respectively; in HLM, the inhibition types of imperatorin and curcumin on macitentan were both mixed. Furthermore, additional molecular docking studies demonstrated that both imperatorin and curcumin occupied the CYP3A4 site. In vivo, the result showed significant increases in AUC(0-t), AUC(0-∞), Tmax, t1/2, and Cmax for macitentan while a decrease in CLz/F when combined with imperatorin. The metabolite ACT-132577 exhibited substantial increases in t1/2, Tmax, and Cmax. Combined with curcumin, the AUC(0-∞) and Tmax of macitentan were significantly increased, while CLz/F was significantly decreased. Conversely, the metabolite ACT-132577 exhibited a substantial decrease in CLz/F, accompanied by notable increases in AUC(0-∞) and Tmax.Conclusion In vitro and in vivo studies revealed that imperatorin and curcumin exhibited inhibitory effects on the metabolism of macitentan. Furthermore, molecular docking revealed that the metabolic inhibition of macitentan by imperatorin and curcumin occurred through binding to the site on CYP3A4. However, further investigation is necessary to ascertain whether this phenomenon will occur in humans.
研究领域:
药理学
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分子生物学
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PubMed
高影响因子
International Journal of Nanomedicine
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2018
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IF 4.37
Hongwei Lin,Qingchun Xie,Xin Huang,Junfeng Ban,Bo Wang,Xing Wei,Yanzhong Chen,Zhufen Lu
Aim The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery.Methods In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated.Results The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis.Conclusion The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.
研究领域:
药学
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药物递送系统
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中药
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PubMed
高影响因子
Scientific Reports
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2026
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IF 4.9
Wang Chengfeng,Wang Jianfeng,Lu Zebei,Wang Yu,Al Mamun Abdullah,Islam Md Siddiqul,Wang Shuanghu,Zhou Yunfang,Xu Minzhi
Abemaciclib is used for the treatment of breast cancer (BC) in clinics. The combination of abemaciclib and imperatorin or isoimperatorin has been studied in vitro and in vivo to explore the pharmacokinetics of Chinese herbs and anti-cancer medicines. Eighteen male SD rats were randomly allocated to three groups: control, isoimperatorin (50 mg/kg) and imperatorin (50 mg/kg). The concentration level of abemaciclib in the plasma was determined using the UPLC-MS/MS technique on rats. Molecular simulation docking with AutoDock 4.2 software and rat liver microsome incubation were utilized to analyze the inhibitory mechanisms. In this study, we found that co-administration of imperatorin and isoimperatorin resulted in higher AUC (0−∞) and C max values and lower CLz/F values ( p < 0.05). In addition, both imperatorin and isoimperatorion showed moderate inhibition for abemaciclib with IC 50 values of 6.79 µM and 6.56 µM, respectively. Intriguingly, we found that imperatorin, isoimperatorin and abemaciclib exhibit similar binding capacities with CYP3A4. Moreover, the results indicated that imperatorin and isoimperatorin significantly impaired the pharmacokinetics of abemaciclib in vivo. Therefore, our research suggests that the combination of abemaciclib and imperatorin or isoimperatorin should be considered more in clinical practice.
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高影响因子
ARCHIVES OF TOXICOLOGY
·
2026
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IF 10.9
Wu Hualu,Cao Lu,Wang Peiqi,Li Ruibin,Wu Jun,Fu Haoxin,Chen Yan,Jiang Shiqi,Xu Ren-ai
Imperatorin (IMP) is a naturally occurring furanocoumarin with a wide range of pharmacological activities, including anti-cancer, anti-inflammatory, and anti-oxidant properties. This study preliminarily investigated the major cytochrome P450 (CYP) enzymes involved in the metabolism of IMP to heraclenin, identifying CYP3A4 as its primary metabolic enzyme. Furthermore, the impact of nine CYP3A4 variants on IMP metabolism was investigated, with CYP3A4.24 demonstrating the lowest relative clearance rate (6.26%). Additionally, the impact of napabucasin on IMP metabolism was investigated, revealing various degrees of inhibition in rat liver microsomes (RLM), human liver microsomes (HLM), and recombinant human CYP3A4. However, no significant alterations in pharmacokinetic parameters were observed during co-administration in rats. Mechanism-based inactivation studies revealed that IMP inactivated CYP2D6 in a time-, concentration-, and NADPH-dependent manner, with kinetic parameters of k inact = 0.024 min⁻¹ and K I = 2.814 µM. The competitive CYP2D6 inhibitor quinidine was found to attenuate this inactivation, while GSH or catalase/SOD did not demonstrate a similar effect. This observation suggested that the active intermediate acted within the enzyme’s active site. Subsequent to oxidation with potassium ferricyanide, there was partial recovery of CYP2D6 activity, thereby confirming the quasi-irreversible inactivator property of IMP. These findings suggested that IMP may exhibit clinically significant interactions with drugs metabolized by CYP2D6.
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BIOCHEMICAL PHARMACOLOGY
·
2020
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IF 4.96
Nan Wang,Jue Wang,Yongjing Zhang,Yingnan Zeng,Shiling Hu,Haoyun Bai,Yajing Hou,Cheng Wang,Huaizhen He,Langchong He
Background Allergic asthma is a common inflammatory lung disease associated with complex pathogenesis. Mast cell (MC) is one of the key drivers of allergic asthma, Mas-related G protein-coupled receptor X2 (MRGPRX2) on the MC could mediate MC activation and trigger a pseudo-allergic reaction. Imperatorin (IMP), the main active compound of Radix Angelicae Dahuricae , has been reported to exert various pharmacological effects. In this study, we focused on the therapeutical mechanism of IMP on MRGPRX2-induced pseudo-allergy and allergic asthma. Methods We examined the effect of IMP on MRGPRX2 related mast cell activation in mouse peritoneal MC (MPMC), Human Laboratory of Allergic Disease 2 MCs (LAD2 cells) and Mrgprx2 -expressing HEK293 cells. Molecular docking and Surface plasmon resonance (SPR) were taken to reveal the binding character between IMP and MRPGRX2. MRGPRX2 downstream proteins were also detected by western blotting . IgE-independent responses was evaluated by using passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) models. The therapeutic effect of IMP on asthma was evaluated by a lung inflammation mouse model which was induced by ovalbumin (OVA). Results IMP was found to reduce substance P (SP) induced calcium flux and suppressed degranulation of MC. SP can promote the phosphorylation of ERK and CamKII, which regulates the synthesis of inflammatory factors such as MIP-2 and TNF-α in MC. In vivo assays revealed that IMP can mitigate SP-induced mouse PCA and ASA. IMP could also mitigate lung inflammation in an OVA induced mice model by inhibiting MC activation in the lung tissue. Furthermore, IMP binds well to MRGPRX2 protein. The binding constant ( K D ) is 4.48 ± 0.49 × 10 −7 M. The data suggeste that IMP is a novel inhibitor of MRGPRX2 to treat allergic asthma.
研究领域:
药理学
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免疫学
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过敏
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呼吸系统疾病
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PubMed
高影响因子
Pharmaceutics
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2026
·Vol. 18
·期 8
·1036
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IF 6.9
Yu Zhang,Jian Guo,Haonan Qiu,Jiale Liu,Chi Zhang,Lutan Zhou,Chunfei Wang,Lihua Li,Xuefeng Hou
Background: Imperatorin (IPT) is a natural furanocoumarin featuring robust anti-inflammatory, antifibrotic and antioxidant activities. However, poor aqueous solubility and insufficient oral bioavailability restrict its clinical application. Multiple gastrointestinal barriers, including the mucus barrier, limited epithelial penetration and P-glycoprotein-triggered drug efflux, are major obstacles hindering IPT oral absorption.Methods: N-acetylcysteine (NAC)-functionalized TPGS conjugates were synthesized first. Using Pluronic®F108 and Lipoid®S-100 as a matrix, imperatorin@N-acetylcysteine-TPGS/Pluronic®F108/Lipoid®S-100 (IPT@NAC-TFS) micelles were fabricated. We characterized their physicochemical features and in vitro release behavior. The Caco-2/HT29-MTX-E12 co-culture cell model was adopted to explore mucus permeation, cellular uptake and transepithelial transport mechanisms. In vivo intestinal distribution and pharmacokinetic tests in rats were carried out to confirm the oral absorption-enhancing effect of micelles.Results: Optimized micelles displayed a uniform shape and favorable encapsulation efficiency. Low CMC maintained structural stability upon gastrointestinal dilution. NAC modification conferred mucus-penetrating capacity on micelles. TPGS simultaneously improved epithelial barrier permeability and inhibited drug efflux, switching IPT transport mode. The micelles effectively cleared intracellular ROS, recovered SOD activity and lowered MDA levels in BLM-impaired MLg fibroblasts. In vivo results revealed enhanced intestinal drug accumulation, with the relative oral bioavailability of IPT increased by 6.07-fold.Conclusions: IPT@NAC-TFS micelles overcome multiple gastrointestinal barriers for oral IPT delivery. Combining mucus penetration, efflux suppression and antioxidative capacity, this system offers a promising strategy to develop oral formulations of poorly soluble antifibrotic natural products.
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