International Journal of Nanomedicine
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2026
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IF 8.7
Pongsigeraxi Borjigin,Caixia Deng,Rilaga Su,Juan Li,Ying Ying,Yingsong Chen,Tegexibaiyin Wang
Purpose This study aimed to enzymatically synthesize pearl powder fluorescent carbon dots (PFCDs) and investigate their neuroprotective potential against cerebral ischemia/reperfusion injury (CIRI) by modulating the Anxa2/NF-κB signaling pathway.Methods PFCDs were synthesized through enzymatic digestion and characterized. Neuroprotective effects were assessed using an in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model in PC12 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. Cell viability, neurological function, cerebral infarct volume, and neuronal injury were evaluated. Expression of Anxa2/NF-κB signaling pathway proteins and inflammatory cytokines (TNF-α, IL-6, IL-1β) was analyzed by Western blot, immunofluorescence, and ELISA.Results The synthesized PFCDs exhibited an organic–inorganic hybrid structure, uniform particle size below 10 nm, and distinctive optical properties. In vitro, PFCDs enhanced cell viability under OGD/R conditions, inhibited phosphorylation of Anxa2 and NF-κB p65, and reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In vivo, treatment with PFCDs in MCAO/R rats improved neurological function, reduced cerebral infarct volume, and alleviated neuronal injury. These protective effects were linked to downregulation of the Anxa2/NF-κB signaling pathway and reduced serum levels of inflammatory cytokines.Conclusion We successfully achieved the enzymatic synthesis of carbon dots from pearl powder, characterized by a unique organic–inorganic hybrid structure. PFCDs effectively alleviated CIRI-induced neuroinflammation by suppressing the Anxa2/NF-κB signaling pathway, highlighting their therapeutic potential as a nanomedicine derived from natural products.
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FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Lang Liu,Jingyu Weng,Lei Yue,Yuanyuan Qin,Jia Yu,Yaqi Li,Shuming Li,Jiaofeng Wu,Yuangui Yang,Zhishu Tang,Hongbo Xu
Cerebral ischemia–reperfusion injury exacerbates neuronal loss following acute ischemic stroke through oxidative stress and regulated cell-death pathways, notably ferroptosis. Here, we investigated whether rosmarinic acid (RA), a natural polyphenol, confers neuroprotection by inhibiting ferroptosis via activation of the KEAP1–NRF2 axis. In vivo , rats pretreated with RA (30 or 60 mg/kg, i.p.) for 14 days before middle cerebral artery occlusion/reperfusion exhibited dose-dependent improvements in neurological scores, reduced infarct volumes, preserved cerebral blood flow, and attenuated histopathological damage. In vitro , RA (25–50 μM) restored the viability of HT22 and PC12 cells subjected to oxygen-glucose deprivation/reperfusion, suppressed lipid reactive oxygen species accumulation, iron overload, and mitochondrial ultrastructural collapse. Mechanistically, RA promoted nuclear factor erythroid 2-related factor 2 (NRF2) nuclear translocation, enhanced antioxidant response element -driven luciferase activity, and upregulated ferroptosis-defense genes ( Gpx4 , Slc7a11 , and Gclm ) at both mRNA and protein levels. Cycloheximide chase and ubiquitination assays, supported by molecular docking, molecular dynamics simulations, and surface plasmon resonance, demonstrated that RA directly binds Kelch-like ECH-associated protein 1 (KEAP1) to stabilize NRF2. A KEAP1 knockdown abolished RA's induction of NRF2 targets and its anti-ferroptotic effects. These findings establish RA as a targeted NRF2 activator and ferroptosis inhibitor, offering a promising therapeutic strategy for limiting ischemia–reperfusion-induced neuronal injury.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2026
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IF 3.8
Li Anan,Lu Shijie,Shang Xueqing,Zhang He,Xie Min,Lu Qiao,Hu Yongjun
Mass spectrometry imaging (MSI) enables spatial mapping of chemical distributions across complex surfaces, with broad applications spanning materials analysis, life sciences, and clinical diagnostics. However, conventional ionization sources often suffer from limited ionization efficiency, creating a trade-off between detection sensitivity and spatial resolution. Post-ionization technology addresses this constraint by incorporating a secondary ionization step, significantly enhancing ionization yield and establishing itself as a leading approach for advancing mass spectrometry techniques. In this study, we have independently developed a vacuum ultraviolet-laser desorption post-ionization mass spectrometry (VUV-LDPI-MS) system, which significantly enhances detection sensitivity through the implementation of post-ionization technology. By integrating low-photon-energy long-wavelength laser desorption with the soft-ionizing capability of VUV light, this technique enhances the detection of chemical species within biological tissues—including both exogenous drugs and endogenous metabolites. The method achieved a theoretical detection limit of 8.3 pg/spot for methylene blue (MB), while markedly reducing substrate effects and sample background interference. Imaging results revealed that endogenous compounds closely aligned with zebrafish tissue anatomy, whereas the spatial distribution of exogenous MB strongly correlated with optical images. Successful application to zebrafish tissue sections enabled clear visualization of both MB and intrinsic metabolites. VUV-LDPI-MSI offers superior ionization efficiency with minimal sample preparation, presenting a robust alternative to conventional LDI-MS approaches and holding considerable promise for future technological development.
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Journal of Functional Foods
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2022
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IF 5.223
Qiyao Wang,Difan Zhang,Jiani Lu,Jiaying Zhang,Zhenquan Xuan,Luyun Gong,Mengxiang Yang,Lingli Jin,Jingyang Le,An Zhu,Hongze Liang,C. Benjamin Naman,Jinrong Zhang,Li Zhao,Shan He,Qinwen Wang,Hao Liu,Xiaojun Yan,Lingling Zhao,Wei Cui
Fucoxanthin is the most abundant marine carotenoid derived from edible brown seaweeds and has been used as a functional ingredient for the treatment of obesity. However, poor brain bioavailability of fucoxanthin has limited its application in combating neurological diseases. In this study, we demonstrated that 40 % fucoxanthin was released from polylactic- co -glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles at one day after incubation. Fucoxanthin nanoparticles (20–40 mg/kg, i.v. ) significantly prevented neurological and behavioral deficits in middle cerebral artery occlusion/reperfusion (MCAO)-treated rats via the reduction of M1 microglial activation, decrease of pro-inflammatory factor production, inactivation of the nuclear factor-κB (NF-κB) pathway, and elevation of the nuclear factor-E2-related factor 2 (Nrf2) pathway in ischemic penumbra. Moreover, fucoxanthin nanoparticles (5–15 μg/mL) inhibited hypoxia-stimulated neurotoxicity in a mouse hippocampal neuron cell line (HT22 cells). These results suggest that fucoxanthin nanoparticles enhanced brain bioavailability and produced neuroprotection against ischemic stroke in vivo with much lower effective concentrations than fucoxanthin itself, providing further support for the development of fucoxanthin as a functional ingredient for the prevention of ischemic stroke with proper nanoparticle formulations.
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International Journal of Electrochemical Science
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2023
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IF 1.5
Ting Ma,Geng Ou
abstract Nimodipine is a widely used calcium antagonist for treatment of a series of cerebrovascular diseases. The fast detection of nimodipine is essential in the clinical applications. This work proposes a β-cyclodextrin modified reduced graphene oxide composite (rGO/β-CD) for electrochemical sensor fabrication. Nimodipine was detected by differential pulse voltammetry (DPV) using proposed electrochemical sensor. Electrochemical data were used to construct a two-stage concentration prediction model combining extreme gradient lift trees (XGBoost) and random forests (RF). This method can improve the detection accuracy and reduce the complexity of the experiment.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2023
·Vol. 46
·期 11
·1527-1534
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IF 2
Bowen Li,Wentao Yu,Lan Yang
Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia–reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 h of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase 3, cleaved caspase 3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.
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ANALYTICAL CHEMISTRY
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2021
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IF 6.986
Zhu-Jun Zhong,Zhong-Ping Yao,Zi-Qi Shi,Yang-Dan Liu,Li-Fang Liu,Gui-Zhong Xin
Nitric oxide (NO) is a molecule of physiological importance, and the function of NO depends on its concentration in biological systems, particularly in cells. Concentration-based analysis of intracellular NO can provide insight into its precise role in health and disease. However, current methods for detecting intracellular NO are still inadequate for quantitative analysis. In this study, we report a quantitative mass spectrometry probe approach to measure NO levels in cells. The probe, Amlodipine (AML), comprises a Hantzsch ester group that reacts with NO to form a pyridine, Dehydro Amlodipine (DAM). Quantification of DAM by ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) allows specific measurement of intracellular NO levels. Notably, the AML/NO reaction proceeds rapidly (within 1 s), which is favorable for NO detection considering its large diffusivity and short half-life. Meanwhile, studies under simulated physiological conditions revealed that the AML response to NO is proportional and selective. The presented UPLC–MS/MS method showed high sensitivity (LLOQ = 0.24 nM) and low matrix interference (less than 15%) in DAM quantification. Furthermore, the mass spectrometry probe approach was demonstrated by enabling the measurement of endogenous and exogenous NO in cells. Hence, the quantitative UPLC–MS/MS method developed using AML as a probe is expected to be a new method for intracellular NO analysis.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2018
·Vol. 410
·期 28
·7357-7371
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IF 3.307
Liu Wei,Wang Ruya,Hu Fan,Wu Pinping,Huang Tao,Fizir Meriem,He Hua
The co-adsorption of mixed nonionic surfactant and imidazolium-based ionic liquid, Triton X100 (TX100), with 1-cetyl-3-methylimidazolium bromide (C 16 mimBr) adsorbed onto the surface of magnetic halloysite nanotubes (MHNTs) was used as an efficient adsorbent for simultaneous determination of amlodipine and nimodipine in urine. The designed adsorbent was characterized by TEM, TGA, FTIR, and DLS analysis methods. All the parameters that influence the extraction efficiency are optimized with the aid of response surface methodology (RSM). The effects of nonionic surfactant TX100 with different structures of ionic-liquid-coated MHNTs were investigated. Under optimum conditions, extraction recoveries of amlodipine and nimodipine were in the range of 73.8–81.2 and 94.3–96.1%, with RSDs ( n = 3) of 2.6–5.5% in spiked urine samples, respectively. The adsorption mechanism principal of mixed hemimicelles was discussed in this study. The limit of detection obtained for analytes was < 0.002 μg·mL −1 . To our knowledge, this was the first attempt using a mixed hemimicelle solid-phase extraction (SPE) based on MHNTs and nonionic surfactant and imidazolium-based ionic liquid for the simultaneous determination of amlodipine and nimodipine in biological samples.
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JOURNAL OF SEPARATION SCIENCE
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2017
·Vol. 40
·期 22
·4311-4319
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IF 2.557
Nani Wang,Qiaoyan Zhang,Hailiang Xin,Dan Shou,Luping Qin
A method using osteoblast membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time-of-flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
Jiale Liu,Kai Liu,Xinyuan Cui,Yujie Ji,Zhaoqi Ding,Zenghui Chang,Junshuo Zhang,Xinyi Wang,Yuanyuan Liu
Donepezil (DNP) is often combined with nimodipine (NMD) for the treatment of Alzheimer's disease (AD). However, its underlying mechanisms remain poorly understood. This study integrated pharmacodynamics, microbiomics, and fecal metabolomics analysis to explore the therapeutic potential and mechanism of DNP + NMD in AD. The results showed that DNP + NMD significantly reduced the contents of serum inflammatory cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) as well as the contents of nitric oxide synthase (NOS), glycogen synthase kinase-3β (GSK-3β) and acetylcholinesterase (AChE) in the hippocampus, alleviated neuronal damage in hippocampal tissues and effectively improved cognitive deficits of AD rats. Furthermore, DNP + NMD greatly increased the relative abundance of beneficial bacteria ( Lactobacillus and Prevotellaceae_ Prevotella ) and decreased the relative abundance of harmful bacteria ( Ruminococcus and Akkermansia ). Fecal metabolomic analyses indicated that DNP + NMD regulated 28 fecal differential metabolite levels mainly through six key pathways, including linoleic acid metabolism, arachidonic acid metabolism, unsaturated fatty acid biosynthesis, steroid hormone biosynthesis, saturated fatty acid biosynthesis, primary bile acid biosynthesis, pantothenic acid biosynthesis, and coenzyme A biosynthesis pathway. Moreover, Spearman's correlation analysis revealed significant associations between affected metabolites and specific gut microbes. In general, our research sheds light that DNP + NMD exerts a neuroprotective effect against AD by ameliorating the gut microbiota and fecal metabolic disorders, uncovering novel mechanistic insights and therapeutic targets for AD intervention.
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Pharmaceutics
·
2025
·Vol. 17
·期 12
·1572
·
IF 5.5
Xiaofeng Wang,Jue Wang,Xia Zhao,Langui Xie,Rui Yang,Chunmeng Sun,Jiasheng Tu,Huimin Sun
Background/Objectives : Polysorbate 80 (PS80), a complex surfactant mixture, is widely recognized for its ability to enhance drug permeation across the blood–brain barrier (BBB). While this effect is generally attributed to the combined actions of its components, the specific contribution and potential selectivity of individual minor components remain poorly understood. This study therefore aimed to isolate and compare the primary minor components of PS80 to determine whether they uniformly enhance BBB permeation or exhibit drug-specific functions. Methods : In this research, four primary minor components of PS80—polyoxyethylene sorbitan monooleate (PSM), polyoxyethylene isosorbide monooleate (PIM), polyoxyethylene sorbitan dioleate (PSD), and a polyethylene glycol/polyoxyethylene sorbitan/polyoxyethylene isosorbide mixture (PEG/PS/PI mixture)—were isolated using preparative liquid-phase chromatography. Drug-loaded formulations were then prepared using the solvent evaporation method incorporating five model drugs: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, MW = 1013.39 Da), donepezil (MW = 379.49 Da), nimodipine (MW = 418.44 Da), chlorogenic acid (MW = 354.31 Da), and paclitaxel (MW = 853.92 Da). The permeability of these formulations across the BBB was evaluated in BALB/c mice after intravenous administration. Brain distribution of the lipophilic dye DiR was assessed using fluorescence imaging, whereas brain homogenate concentrations of therapeutic drugs were quantified by UPLC-MS/MS. Results : Results revealed that the enhancement of brain delivery was dependent on both the specific minor component and the drug. The PEG/PS/PI mixture specially enhanced the brain homogenate concentration of donepezil to 11.8 ± 1.2 ng/mL, representing a 6.9-fold enhancement, while PIM micelles increased the delivery of DiR, donepezil, and nimodipine. In contrast, PSM and PSD micelles improved transport of only DiR and donepezil. The broad performance of PIM suggests a more flexible formulation—a hypothesis that warrants further validation. Conversely, none of the different minor components enhanced the delivery of chlorogenic acid or paclitaxel, underscoring the critical role of specific drug–component interactions. Conclusions : This component-resolved insight challenges the conventional perception of PS80 and provides a rational framework for engineering precision brain-targeted delivery systems by selecting functional minor components.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Xingfang Zhang,Liang Gao,Jianv Wang,Wei Zhang,Dong Xu,Yanhua Wang,Tianlong Liu,Kai Gao,Zhen Ren,Yi Ding
β-Bisabolene, a bioactive sesquiterpene extracted from myrrh—a substance utilized for ischemic stroke treatment—has known therapeutic potential. Nevertheless, the exact mechanisms underlying its beneficial effects on ischemic stroke, along with its potential targets, remain to be fully elucidated. This study aimed to investigate the therapeutic potential of β-Bisabolene in ameliorating ischemic stroke, identify its potential targets and interactions, and explore the underlying pathways involved. Bioinformatics analyses, including network pharmacology and analysis of GEO transcriptomic datasets, were performed to predict the potential targets and mechanisms of β-Bisabolene in ischemic stroke treatment. Preliminary computational validation was achieved through molecular similarity comparisons, molecular docking studies, and molecular dynamics simulations. In vitro experiments were then conducted to confirm the protective effects of β-Bisabolene on microglia injured by oxygen‒glucose deprivation and to validate the findings from the bioinformatics analyses. The results revealed that β-Bisabolene reduces the levels of the proinflammatory cytokines TNF-α, IL-1β and NO; decreases reactive oxygen species levels; and decreases the expression of COX-2, P38, ERK and Keap1. Moreover, it increases the expression of Arg-1, Nrf2, NQO1 and HO-1. These effects are associated with improved survival rates of oxygen–glucose deprivation–damaged microglia. In conclusion, β-Bisabolene may exert anti-inflammatory and antioxidant effects to ameliorate microglial injury induced by ischemic stroke by antagonizing COX-2 and mediating the MAPK signaling pathway and Keap1/Nrf2 pathway. This study provides valuable insights into the therapeutic potential of β-Bisabolene for the treatment of ischemic stroke.
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