RARE METALS
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2025
·
IF 11
Deng Shu-Yue,Zhou Xin-Yu,Zou Xiao-Peng,Tang Fang,Yang Dong,Sun Cai-Xia,Luo Jun,Ge Xing,Zhu Jia-Ying,Fang Tian-Ye,Yue Cai-Feng,Ju Yan-Min,Dai Jian-Jun
The presence of the blood–brain barrier limits the drug concentration in the brain, while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance, making the clinical treatment of bacterial meningitis challenging. Herein, a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis, to overcome the low drug concentration and drug resistance. This strategy was achieved by a protein-supported Au nanozyme (ANZ). With a particle size of less than 10 nm, it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H 2 O 2 . Benefiting from the cascade catalytic amplification effect generated by its dual enzyme-like activities, ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro. Notably, small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration. In a mouse model of bacterial meningitis, the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone. Additionally, the meningitis mice exhibited undamaged cognitive and behavioral abilities, indicating the excellent biocompatibility of ANZ. The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation, strong antibacterial efficacy and does not lead to bacterial resistance. It holds broad prospects for the treatment of bacterial meningitis. Graphical abstract
研究领域:
医学
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药理学
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纳米医学
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产品关联
DOI
高影响因子
Natural Product Communications
·
2025
·
IF 1.4
Zhuowei Shen,Yanhong Chen,Kui Zeng,Haihong Hu,Jie Pan,Mingcheng Xu,Kaifeng He,Fengting Ou,Lushan Yu,Su Zeng,Lu Chen
Background6-hydroxykynurenic acid (6-HKA), isolated from Ginkgo biloba leaves, has demonstrated neurorestorative properties against cerebral ischemia in middle cerebral artery occlusion (MCAO) mice models. However, our previous studies showed that 6-HKA was difficult to penetrate the blood brain barrier (BBB) to exert its pharmacological effects in rats. Therefore, this study aims to investigate the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice, to determine whether the ability of 6-HKA to cross the BBB is contingent upon barrier integrity.MethodsThis study established and validated the ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) methods for the quantification of 6-HKA in mouse plasma and brain, and investigated the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice and sham-operated mice.ResultsThis study demonstrates that the mean residence time (MRT0−t) of 6-HKA in the MCAO group was significantly prolonged compared to the sham-operated group, and there was a higher distribution of 6-HKA in the ischemic cerebral cortex than in the contralateral normal cerebral cortex.ConclusionThis study illustrated that in MCAO mice, the prolonged MRT0−t of 6-HKA and the increased permeability of BBB made the accumulation of 6-HKA in the ischemic cerebral cortex, thereby enabling 6-HKA to exert neurorestorative effects.
研究领域:
神经科学
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药理学
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生物化学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 37
·31101-31106
·
IF 3.289
Ailing Hui,Shijing Zhu,Huayang Yin,Li Yang,Zheng Zhang,An Zhou,Jian Pan,Wencheng Zhang
A series of ginkgolide B derivatives (GBD) were designed for delivery of ginkgolide B (GB) across the blood–brain barrier to the brain. Three GBD had shown considerable brain-targeting ability in our previous study. Among them, the ginkgolide B pyrazine (PGB) derivative was selected as a promising novel GB derivative because of its highest brain distribution. Further investigations with regard to PGB and GB's effects on inhibiting the expression of P-gp and attenuating the efflux function of P-gp were reported in this study. They were considered a big step towards better understanding the relationship between GBD's brain-targeting behavior and P-gp regulation. Western blot analysis indicated that PGB was more effective in inhibiting the expression of P-gp than GB in rat brain microvessel endothelial cells (rBMECs) and rat cerebral cortexes and hippocampus. Moreover, the efflux function of P-gp via the transportation of rhodamine 123 was significantly inhibited in PGB-treated rat brains. Preventive medication with PGB induced a better protection of the integrity of the BBB in incomplete ischemia mice. Our findings revealed that an attenuated expression level and efflux function of P-gp and improved protective effect could be realized by the ginkgolide B derivative. These investigations will pave the way for designing more efficient brain-targeting derivatives of ginkgolide and some other central nervous system drugs.
研究领域:
药理学
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神经科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Fanfei Meng,Sajid Asghar,Yurui Xu,Jianping Wang,Xin Jin,Zhilin Wang,Jing Wang,Qineng Ping,Jianping Zhou,Yanyu Xiao
Many nanoparticle matrixes have been demonstrated to be efficient in brain targeting, but there are still certain limitations for them. To overcome the shortcomings of the existing nanoparticulate systems for brain-targeted delivery, a lipoprotein resembling protein-free nanostructured lipid carrier (PS80-NLC) loaded with curcumin was constructed and assessed for in vitro and in vivo performance. Firstly, single factor at a time approach was employed to investigate the effects of various formulation factors. Mean particle sizes of ≤100 nm, high entrapment efficiency (EE, about 95%) and drug loading (DL, >3%) were obtained for the optimized formulations. In vitro release studies in the presence of plasma indicated stability of the formulation under physiological condition. Compared with NLC, PS80-NLC showed noticeably higher affinity for bEnd.3 cells (1.56 folds greater than NLC) but with lower uptake in macrophages. The brain coronal sections showed strong and widely distributed fluorescence intensity of PS80-NLC than that of NLC in the cortex. Ex vivo imaging studies further confirmed that PS80-NLC could effectively permeate BBB and preferentially accumulate in the brain (2.38 times greater than NLC). The considerable in vitro and in vivo performance of the safe and biocompatible PS80–NLC makes it a suitable option for further investigations in brain targeted drug delivery .
研究领域:
药剂学
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神经科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
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2022
·
IF 6.058
Wei Wang,Qiu-Yuan Gong,Lin Cai,Yao Jing,Dian-Xu Yang,Fang Yuan,Hao Chen,Heng-Li Tian
Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment.
研究领域:
神经科学
·
分子生物学
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神经病学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Shanshan Hu,Zhiyuan Lin,Sibo Zhao,Bowen Zhang,Liyong Luo,Liang Zeng
Brain inflammation develops with increased colitis . Pu-erh tea is considered a potential dietary intervention to improve colitis. However, it's unclear whether Pu-erh tea helps alleviate colitis-mediated brain dysfunction . Here, we found that colitis triggered brain dysfunction and increased the risk of depression. Pu-erh tea improved gut-brain barrier function (increased ZO-1 and Occludin) and restored short-chain fatty acids (SCFAs) as well as neurotransmitter release (γ-GABA, 5-HT, and dopamine), which stemmed from the production of butyric acid (BA). Pu-erh tea and BA promoted the production of SCFAs by reshaping the gut microbes (increased Lactobacillus , Akkermansia , Faecalibaculum ), thereby downregulating gut inflammatory protein expression (PI3K/AKT/NF-κB). SCFAs, especially BA, intervened directly in the blood-brain barrier via the gut-brain axis to restore neurotransmitter release. Collectively, our results highlighted that increasing BA through Pu-erh tea consumption may be a key mechanism for improving colitis-mediated brain dysfunction by lowering gut inflammation and balancing gut microbe-gut-brain axis homeostasis . These results provide a promising step that might encourage further investigations of Pu-erh tea as a protective agent for brain function in colitis patients.
研究领域:
胃肠病学
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神经科学
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微生物学
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营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2023
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IF 5
Shuang Zhou,Yuhua Li,Yi Hong,Zhitao Zhong,Min Zhao
Puerarin (Pue), an isoflavone compound extracted from Pueraria, has been shown to inhibit inflammation and reduce cerebral edema. The neuroprotective effect of puerarin has attracted much attention in recent years. Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis that causes damage to the nervous system. This study aimed to investigate the effect of puerarin on SAE and elucidate the potential underlying mechanisms. A rat model of SAE was established by cecal ligation and puncture, and puerarin was injected intraperitoneally immediately after the operation. Puerarin was found to improve the survival rate and neurobehavioral score of SAE rats, alleviate symptoms, inhibit the level of brain injury markers NSE and S100β, and improve the pathological changes in rat brain tissue. Puerarin was also found to inhibit the level of factors related to the classical pathway of pyroptosis, such as NLRP3, Caspase-1, GSDMD, ASC, IL-1β, and IL-18. Puerarin also reduced the brain water content and penetration of Evan’s Blue dye in SAE rats, and reduced the expression of MMP-9. In the in vitro experiments, we further confirmed the inhibitory effect of puerarin on neuronal pyroptosis by establishing a pyroptosis model in HT22 cells. Our findings suggest that puerarin may improve SAE by inhibiting the classical pathway of NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing blood-brain barrier damage, thus playing a role in brain protection. Our study may provide a novel therapeutic strategy for SAE.
研究领域:
神经科学
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药理学
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免疫学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 11
·3998-4008
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IF 6.6
Mingxi Yang,Xin Wei,Kaibo Pan,Zeli Zhou,Yang Liu,Xiaodan Lv,Bai Yang
Ischemic stroke (IS) is a leading cause of death in the world, and there is still a lack of effective treatments. Ginkgolide B (GB) can antagonize the platelet activating factor receptor and has shown a significant curative effect on cerebral ischemia. However, GB and other drugs for IS have shown poor clinical efficacy due to their inability to cross the blood–brain barrier (BBB). Herein, red fluorescent carbonized polymer dots (CPDs) were developed as biocompatible nanocarriers to deliver GB to the brain tissue. Both in vivo and in vitro experiments verified the ability of GB-CPDs to penetrate the BBB, and GB-CPDs remained in the brain significantly longer than unmodified CPDs. In a rat model of middle cerebral artery occlusion (MCAO), circulatory administration of GB-CPDs effectively reduced cerebral infarct size and neuronal apoptosis, with a significantly better therapeutic effect compared to GB. This study provided a novel GB-based nanodrug that could target the brain with improved efficacy, showing great application potential in central nervous system diseases.
研究领域:
神经科学
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药学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2025
·
IF 3.9
Jing Jiang,Yue Xing,Shumeng Liu,Yue Na,Xia Lei,Fang Geng,Yafeng Zhang,Lihong Yang,Ning Zhang
Naringin (4',5,7-trihydroxyflavanone-7-rhamnoglucoside, NG), a potential treatment for Alzheimer’s disease (AD), has strong neuroprotective effects but is limited by poor solubility, low bioavailability, and limited brain accumulation. To address these issues, we developed ANG-NG-NPs, a novel NG-loaded poly (ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) nanoparticle modified with the brain-targeting peptide Angiopep-2 (TFFYGGSRGKRNNFKTEEY, ANG). ANG-NG-NPs exhibited an average size of 126.1 ± 4.50 nm, a zeta potential of -2.97 ± 0.29 mV, 73.43% ± 0.80% encapsulation efficiency (EE), and 24.68% ± 0.45% drug loading capacity (LC). In vitro release studies confirmed its sustained-release properties. In vivo, ANG-NG-NPs extended NG’s circulation time and increased brain uptake. Notably, ANG-NG-NPs restored learning and memory in APP/PS1 mice, improved hippocampal cell health, and reduced hyperphosphorylated tau protein (p-Tau) expression. These findings suggest ANG-NG-NPs as a promising brain-targeting system for treating central nervous system disorders.
研究领域:
药剂学
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神经科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2012
·Vol. 17
·期 10
·12049-12060
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IF 2.386
Zhi Long Liu,Ligang Zhou,Shu Shan Du
The aim of this research was to determine the chemical composition and insecticidal activity of the essential oil ofCurcuma wenyujinY.H. Chen et C. Ling rhizomes against the booklouseLiposcelisbostrychophilaBadonnel and to isolate any insecticidal constituents from the essential oil. The essential oil ofC. wenyujinrhizomes was obtained by hydrodistillation and analyzed by GC-MS. A total of 43 components of the essential oil were identified and the principal compounds in the essential oil were 1,8-cineole (15.26%), camphor (10.12%), germacrone (6.86%), β-elemene (6.33%), curzerene (6.70%), and β-elemenone (5.23%). followed by curzerenone (4.52%), curdione (4.45%) and linalool (4.43%). Based on bioactivity-guided fractionation, the two main active constituents were isolated from the essential oil and identified as 1,8-cineole and camphor. The essential oil ofC. wenyujinrhizomes exhibited contact toxicity againstL. bostrychophilawith an LD50value of 208.85 µg/cm2. Camphor (LD50= 207.26 µg/cm2) exhibited stronger contact toxicity than 1,8-cineole (LD50= 1048.75 µg/cm2) against booklouse. The essential oil ofC. wenyujin(LC50= 2.76 mg/L air) also possessed fumigant toxicity againstL. bostrychophila, while the two constituents, camphor and 1,8-cineole had LC50values of 1.03 mg/L air and 1.13 mg/L air, respectively. The results indicate that the essential oil ofC. wenyujinrhizomes and its constituent compounds have potential for development as natural insecticides or fumigants for control of insects in stored grains.Keywords:Liposcelisbostrychophila;Curcuma wenyujin;contact toxicity;fumigant;essential oil composition;1,8-cineole;camphor
研究领域:
植物学
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昆虫学
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天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2015
·
IF 2.979
Hua Li,Dan Li
In this study, a novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of enkephalins was synthesized and prepared in a micropipette tip using epitope imprinting technique. The synthesized MIPs were characterized by scanning electron microscope (SEM) and infrared spectroscopy. A molecularly imprinted solid-phase microextraction (MISPME) method was developed for extraction of enkephalins in aqueous solutions. The parameters affecting MISPME were optimized. The results indicated that this MIP monolith exhibited specific recognition capability, high enrichment efficiency and excellent reusability for enkephalins. MALDI-TOF MS analysis demonstrated that this MIP monolith can act as a useful tool for highly selective purification and enrichment of enkephalin, a kind of low abundance protein, from high-abundance proteins in human cerebrospinal fluids (CSF). Employed this MIP monolith as solid-phase microextraction column, quantitative assay of enkephalins in human CSF was developed by HPLC–ultraviolet (UV) detection in this work. The detection limits were 0.05–0.08 nM. This MISPME/HPLC–UV method was used to quantify Met-enkephalin and Leu-enkephalin levels in the CSF of patients with cancer pain.
研究领域:
分析化学
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医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-16
·
IF 6.1
Lin Renbao,Luo Rui,Yu Xinyue,Zou Junjie,Huang Xiaowei,Guo Yanwu
Background Status epilepticus (SE) is a common severe neurological emergency. Cerebral edema caused by SE is unavoidable and may exacerbate epilepsy. Recent studies have identified cerebrospinal fluid (CSF) as a crucial fluid source of initial cerebral edema following ischemic stroke and cardiac arrest. Moreover, synchronized neuronal firings drive CSF influx into interstitial fluid (ISF). Parenchymal border macrophages (PBMs) have been found to play a role in regulating CSF flow dynamics. However, the involvement of CSF and PBMs in cerebral edema during SE remains unclear. Here, we investigated the fluid source of cerebral edema in the initial phase of SE with the role of PBMs involved.Methods Lithium chloride-pilocarpine was used to induce SE in C57BL/6 J mice. Electroencephalogram (EEG) was acquired to assess changes in relative EEG power pre- and post-seizure onset. Apparent diffusion coefficient (ADC) maps reconstructed from diffusion-weighted imaging (DWI) were utilized to evaluate cytotoxic edema. Blood–brain barrier (BBB) permeability was examined using sodium fluorescein (NaFl). CSF tracer influx into the brain was assessed by transcranial imaging and brain slices. PBMs were depleted using clodronate liposomes. Immunohistochemistry was used to evaluate PBM depletion, severity of vasogenic edema, inflammation, and neuronal damage.Results During the initial stage of SE, relative EEG power sharply increased and ADC values significantly decreased. Concurrently, CSF tracer influx into the cortex significantly elevated, though NaFl leakage from blood to brain parenchyma did not evidently alter. Following depletion of PBM, CSF influx declined but AQP4 expression and polarization remained unaffected. Post-PBM depletion, there was no significant alteration in relative EEG power, yet CSF influx decreased substantially during the initial stage of SE. The degree of ADC decline lessened, IgG extravasation after SE decreased, activated microglia and proliferating astrocytes count fell, and neuronal damage post-SE alleviated.Conclusion sCSF appeared to contribute to cerebral edema in SE. Depletion of PBM alleviated cytotoxic edema in the initial phase of SE, and subsequent vasogenic edema, inflammatory response and neurological damage were reduced. These findings may provide potential novel strategies for treating cerebral edema following SE.
研究领域:
神经科学
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免疫学
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神经影像学
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药理学
✓ 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）