Journal of Zhejiang University-SCIENCE B
·
2018
·
IF 1.815
Mei-qing Jin,Dong Zhang,Ying Zhang,Shan-shan Zhou,Xian-ting Lu,Hong-ting Zhao
Decabromodiphenylethane (DBDPE) has been widely used as an alternative flame retardant due to the restriction or phase-out of traditional polybrominated diphenyl ethers (PBDEs), and is of increasing concern regarding its ubiquity, persistence, and potential adverse effects. In the present study, the toxicological effects of DBDPE were evaluated using zebrafish as an in vivo model. Upon being exposed to DBDPE-polluted sediments for a short term, it was found that the mortality and malformation of zebrafish (including edema, bent notochord, and bent tail) were not affected even at the highest concentration tested (1000.0 µg/kg dry sediment). Regarding behavioral responses, it was found that zebrafish larvae of 48 hours post fertilization (hpf) in all groups escaped successfully with a touch to the dorsal fin. However, when exposed to the highest DBDPE concentration, the larvae of 120 hpf exhibited significantly smaller distances as compared to the control. Moreover, the results of the acetylcholinesterase (AChE) activity, the expression levels of two important nerve-related genes, and the cell apoptosis all indicated that DBDPE posed low neurotoxicity in embryo-larval zebrafish. The results in this study shed some light on the potential risks of DBDPE in the real environment and highlight the application of the sediment exposure route in the future.
研究领域:
环境毒理学
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水生生物学
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神经科学
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DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 17
·3489
·
IF 4.6
Xiaohua Wang,Minglan Ma,Yalan Feng,Jian Liu,Gang Wang
A novel series of multifunctional tacrine–quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer’s agents. These compounds incorporate tacrine for cholinesterase’s inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation–π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds16e(IC50= 0.10 μM for AChE, 0.043 μM for BuChE) and16h(IC50= 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-induced Aβ1–42aggregation (16e: 80.5% ± 4.4%, 16h: 93.2% ± 3.9% at 20 μM). Kinetic analyses revealed mixed-type inhibition, suggesting dual binding to both CAS and PAS of AChE. UV–vis spectrometry confirmed the chelation of Cu2+and Zn2+ions by the 8-hydroxyquinoline moiety. These findings highlight the tacrine–quinoline scaffold as a promising platform for the discovery of a multitarget-directed anti-AD drug.
研究领域:
药物化学
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神经药理学
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生物有机化学
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药物设计
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阿尔茨海默病研究
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DOI
PubMed
高影响因子
Food Bioscience
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2022
·
IF 5.318
Jingru Zheng,Yuanhong Gao,Jie Ding,Na Sun,Songyi Lin
The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) peptides on scopolamine-caused memory impairment in mice. Behavioral experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of mice. In comparison with the scopolamine group, the two peptides at a dose of 40 mg/kg could improve memory impairment. The serum SOD activity (82.82 ± 0.19 vs 79.47 ± 2.42 U/mg prot) and hippocampal ACh level (101.46 ± 3.23 vs 99.85 ± 7.13 μg/mg prot) of SSDAFFPFR were higher than those of SNVFDMF. Hippocampal AChE activity (0.20 ± 0.03 vs 0.53 ± 0.02 U/mg prot), hippocampal MDA level (1.56 ± 0.01 vs 1.63 ± 0.05 nmol/mg prot) and the serum MDA level (3.38 ± 0.24 vs 3.88 ± 0.21 nmol/mg prot) was lower than that of SNVFDMF. The state of mouse hippocampal cells was further observed by a microscopic imaging system. In addition, western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax, caspase-3, and p53, and promote the expression of BCL-XL, CREB, and BDNF, thus protecting hippocampal neurons in mice. In conclusion, the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.
研究领域:
神经科学
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药理学
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生物化学
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产品关联
DOI
高影响因子
NEUROTOXICOLOGY
·
2023
·
IF 3.4
Tong Zhang,Chunmei Zhang,Yuyou Luo,Shuping Liu,Siyuan Li,Lixia Li,Yuxin Ma,Jing Liu
The present study aimed to investigate the protective effect of rutin on the injury of spinal motor neuron in rats exposed to acrylamide (ACR) the underlying mechanism. Fifty male Sprague-Dawley rats, aged 7–8 weeks, were randomly divided into control group, ACR group (20 mg/kg), low dose(100 mg/kg), medium dose (200 mg/kg) and high dose(400 mg/kg) rutin groups, ten rats in each group. The rats were given intragastric administration for 21 days. Every week, a neurobehavioral test was conducted. Nissl staining was used to observe the morphological changes in motor neurons in the L4-L6 segment of the spinal cord . Immunohistochemistry was used to identify AChE and ChAT in the rat spinal cord. Western blot was used to identify the expression of AChE, ChAT, P-ERK, ERK, and Nrf2 proteins in the rat spinal cord. The commercial kits were used to detect the presence of SOD, GSH, and LDH in the rat spinal cord. At the start of the second week, the medium and high dosage rutin group's rats' gait scores significantly decreased as compared to those of the ACR group. When rutin dosage was increased, the Nissl staining revealed that Nissl bodies was staining intensified compared to the ACR group. Immunohistochemistry and Western blot analysis revealed that AChE and ChAT expression changed when rutin dose was raised, but P-ERK and Nrf2 expression steadily increased in the spinal cord of rats in the medium and high dose groups compared to the ACR group. In the spinal cord of rats in each dosage group compared to the ACR group, the findings of the oxidative stress indices demonstrated that the expression levels of SOD and GSH rose with the increase of rutin dose, while the expression of LDH reduced with the rise of rutin dose. Rutin has an anti-oxidative impact through up-regulating the expression of P-ERK and Nrf2 proteins in the ERK/Nrf2 pathway, which may be connected to its protective action on motor neurons in the spinal cord of rats exposed to ACR.
研究领域:
神经科学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2020
·
IF 3.044
Cai-Ping Yao,Jing Li,Jian-Feng Liu,Zhen-Xing Zou,Feng-Hua Kang,Xiao-Min Li,Dai Li,Kang-Ping Xu,Ping-Sheng Xu,Gui-Shan Tan
Seven undescribed C 27 steroidal glycosides , Seladelicatulasine A–G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC 50 values of 0.31, 0.09, and 0.04 μ M, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC 50 values of 0.37 and 0.65 μ M, respectively.
研究领域:
药用植物学
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天然产物化学
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生物化学
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神经药理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Shaochun Shi,Huibin Wang,Jian Wang,Yvxi Wang,Xiaobian Xue,Zilin Hou,Guo-Dong Yao,Xiao-Xiao Huang,Hongwei Zhao,Qingbo Liu,Shao-Jiang Song
7- O -galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β -amyloid (A β ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of A β aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC 50 , 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC 50 , 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H 2 O 2 -induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
研究领域:
药理学
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神经科学
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药物化学
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
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2024
·
IF 3.3
Huizhen Sun,Shanshan Wei,Yanchun Gong,Kaizhi Ding,Shan Tang,Wei Sun,Chunhua Yuan,Liping Huang,Zhibing Liu,Chong Chen,Lihua Yao
ABSTRACT Glutamate is a neurotransmitter that can cause excitatory neurotoxicity when its extracellular concentration is too high, leading to disrupted calcium balance and increased production of reactive oxygen species (ROS). Cordycepin, a nucleoside adenosine derivative, has been shown to protect against excitatory neurotoxicity induced by glutamate. To investigate its potential neuroprotective effects, the present study employed fluorescence detection and spectrophotometry techniques to analyze primary hippocampal-cultured neurons. The results showed that glutamate toxicity reduced hippocampal neuron viability, increased ROS production, and increased intracellular calcium levels. Additionally, glutamate-induced cytotoxicity activated acetylcholinesterase (AChE) and decreased glutathione (GSH) levels. However, cordycepin inhibited glutamate-induced cell death, improved cell viability, reduced ROS production, and lowered Ca 2+ levels. It also inhibited AChE activation and increased GSH levels. This study suggests that cordycepin can protect against glutamate-induced neuronal injury in cell models, and this effect was inhibited by adenosine A 1 receptor blockers, indicating that its neuroprotective effect is achieved through activation of the adenosine A 1 receptor.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2019
·
IF 4.027
Yu-Heng Hu,Jie Yang,Yun Zhang,Ke-Chun Liu,Teng Liu,Jie Sun,Xiao-Jing Wang
The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
研究领域:
药理学
·
神经科学
·
药物设计
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Dianfa Zhao,Jie Liu,Yunshan Zhou,Lijuan Zhang,Yuxu Zhong,Yang Yang,Baoquan Zhao,Mengru Yang,Yong’an Wang
It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood–brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2–7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood–brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
研究领域:
药学
·
纳米技术
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神经科学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-18
·
IF 4.122
Zhou Bohang,Zhang Bingyu,Li Xingqiang,Liu Xiuxiu,Li Hui,Li Ding,Cui Zhiming,Geng Huiling,Zhou Le
A series of 2-aryl-9-methyl- β -carbolinium bromides (B) were synthesized and explored for anti-acetylcholinesterase (AChE) activities in vitro , action mechanism and structure-activity relationship. All the compounds B along with their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10 μM. Thirteen compounds B showed the excellent activity with IC 50 values of 0.11 – 0.76 μM and high selectivity toward AChE relative to butyrylcholinesterase (BChE), superior to galantamine (IC 50 = 0.79 μM), a selective AChE inhibitor drug. Kinetic analysis showed that the action mechanisms of both compounds B and A are a competitive inhibition model. Structure-activity relationship analyses showed that the C = N + moiety is a determinant for the activity. Substituents at 6, 7 or 4′ site, the indole-N-alkyl and the aromatization of the C-ring can significantly improve the activity. Molecular docking studies showed that the compounds could combine with the active site of AChE by the π-π or cation-π action between the carboline ring and the phenyl rings of the residues, and the β-carboline moiety is embedded in a cavity surrounded by four aromatic residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, 2-aryl-9-methyl- β -carboliniums emerged as novel and promising tool compounds for the development of new AChE inhibitor agents.
研究领域:
药理学
·
有机化学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2022
·
IF 6.449
Chuks Fidelis Nwanade,Min Wang,Hongxia Li,Abolfazl Masoudi,Zhijun Yu,Jingze Liu
Plant essential oils (EOs) are usually complex mixtures of volatile compounds, and these compounds can vary in composition as a result of biotic and abiotic factors. Thus, understanding the contribution of the individual compounds particularly their interactions with respect to acaricidal activity is important for the use of EOs as an alternative to synthetic acaricides . Herein, the acaricidal activity of constituents from EOs of cinnamon ( Cinnamomum zeylanicum and Cinnamomum cassia ) against Haemaphysalis longicornis was investigated using the nymphal and adult immersion tests. Among the test compounds, benzyl benzoate showed the highest toxicity against the nymphs (LC 50 = 24.41 µL/mL) and adults (LC 50 = 3.99 µL/mL). All combinations at their sublethal concentration (LC 30 ) exhibited synergy. The binary mixture of benzyl benzoate + cinnamaldehyde presented the highest synergy ratio (3.42) while tertiary mixtures of cinnamaldehyde + eugenol + linalool showed the least synergy ratio (1.20). Enzyme assays revealed that benzyl benzoate significantly inhibited AChE activity ( p < 0.05). The ecotoxicological assessments of benzyl benzoate and cinnamaldehyde indicate likely minimal effects on non-target terrestrial invertebrate, Tenebrio molitor . On the other hand, they were toxic to non-target aquatic species , Daphnia magna . Based on our results, the acaricidal activity of cinnamon EO against H . longicornis may be linked to the content of benzyl benzoate whose presence may be synergistic to the activity of other compounds.
研究领域:
昆虫学
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药理学
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毒理学
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植物科学
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产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2024
·
IF 4.3
Xiujuan Huang,Yuanyuan Cheng,Qi Zhou,Yifeng Tu,Jilin Yan
Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01–8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.
研究领域:
分析化学
·
生物化学
·
酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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