检索结果-南通市图书馆

Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

Synthesis and evaluation of peptide-fentanyl analogue conjugates as dualμ/δ-opioid receptor agonists for the treatment of pain

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2022年第8期33卷 4107-4110页

作者： Jing Li Tao Zhang Jialin Sun Fengxia Ren Hongxin Jia Zixing Yu Jingchao Cheng Weiguo Shi State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China School of Chemical Engineering and Technology Tianjin UniversityTianjin 300350China

Novel peptide-fentanyl analogue conjugates were synthesized by the covalent coupling of carfentanyl derivatives to the C-terminus or N-terminus of the conformationally constrained dermorphin tetrapeptide BVD03 via a chemical linker.The carfentanyl-related analogues displayed distinct binding and functional activities atμ/δopioid receptors(MOR/DOR)and antinociceptive effects when conjugated to the peptide.The most potent compound,SW-LJ-11,displayed mixed MOR/DOR agonist properties in the low nanomolar range and significant analgesic efficacy in vivo in four classic mouse models of pain.Interestingly,SW-LJ-11 did not exhibit any physical dependence or respiratory depression,in contrast to an equipotent analgesic dose of morphine or BVD03,indicating that the use of opioid peptide-fentanyl analogue conjugates as dual MOR/DOR agonists may be a promising strategy for obtaining safer opioids.

关键词： Peptide-small molecule conjugates Dual MOR/DOR agonists Lead compound Analgesics Physical dependence

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System

在线全文

学校读者我要写书评

暂无评论

Neuroscience Bulletin 2023年第11期39卷 1655-1668页

作者： Rong-Rong Hu Meng-Die Yang Xiao-Yan Ding Ning Wu Jin Li Rui Song State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of NeuropsychopharmacologyBeijing Institute of Pharmacology and ToxicologyBeijing100850China Department of Nuclear Medicine Hainan Hospital of Chinese PLA General HospitalSanya572013China

Opioid use disorder(OUD)has become a considerable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor(D3R)have effects on addiction in different animal models.We have previously reported that YQA14,a D3R antagonist,exhibits very high affinity and selectivity for D3Rs over D2Rs,and is able to inhibit cocaine-or methamphetamine-induced reinforcement and reinstatement in self-administration tests.In the present study,our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats,also attenuated heroin-induced reinstatement of drug-seeking behavior.On the other hand,YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice.Moreover,we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system.These findings suggest that D3R might play a very important role in opioid addiction,and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

关键词： Opioid use disorder D3 receptors Dopamine Self-administration Conditioned place preference

Active fraction combination from Liuwei Dihuang decoction(LW-AFC) ameliorates corticosterone-induced long-term potentiation impairment in mice in vivo

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第6期33卷 436-437页

作者： HUANG Yan LI Dong CHENG Bin LIU Gang ZHANG Yong-xiang ZHOU Wen-xia Beijing Institute of Pharmacology and toxicology State Key Laboratory of Toxicology and Medical Countermeasures

Liuwei Dihuang decoction(LW), a classic formula in traditional Chinese medicine(TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6herbs including Dihuang[prepared root of Rehmannia glutinosa(Gaertn) DC], Shanyao(rhizome of Dioscorea polystachya Turcz), Shanzhuyu(fruit of Cornus officinalis Siebold Zucc), Mudanpi(root bark of Paeonia × suffruticosa Andrews),Zexie(rhizome of Alisma plantago-aquatica L) and Fuling(scleorotia of Wolfiporia extensa(Peck) Ginns)LW-active fraction combination(LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. There are 3 fractions in LW-AFC, a polysaccharide fraction(LWB-B), a glycoside fraction(LWD-b) and an oligosaccharide fraction(CA-30). Our previous results indicate that LW-AFC has similar pharmacological effects to LW, modulating the balance of the NIM network. LW-AFC has positive effects in many animal models of kidney deficiency or disturbance of the NIM network. LW-AFC could improve the cognitive ability in Alzheimer′s disease(AD) animal models(APP/PS1, SAMP8), where modulating immune function and balancing the NIM network may play an important role in its cognition improving effects. Our study also showed that LW-AFC had protective effects on stress-induced disturbances of the NIM network. However, the underlying mechanisms remain elusive and need further investigation. OBJECTIVE This study evaluated the effects of LW-AFC and the active fractions(polysaccharide, LWB-B;glycoside, LWD-b;oligosaccharide,CA-30) on corticosterone(Cort)-induced long-term potentiation(LTP) impairment in vivo. METHODS LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration(ig, ip, 7 d) or single administration(icv, ig, ip). Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS) to induce LTP impairment. Moreover, in order

关键词： LW-active fraction combination active fractions corticosterone long-term potentiation synaptic plasticity stress

SOD mimicAEOL-10150 improve lifespan and delay brain aging via inhibition of senescence-associated secretory phenotype in SAMR1 strain

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2017年第10期31卷 983-984页

作者： Xiao-rui ZHANG Xiao-rui CHENG Jian-hui WANG Ju ZENG Ding-ding MA Hong-chao ZHANG Wen-xia ZHOU Yong-xiang ZHANG State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology

OBJECTIVE To observe the anti-aging effects of SOD mimic AEOL^(-1)0150 in antisenescence accelerated mouse resistant 1(SAMR1)strain.METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL^(-1)0150 2 mg·kg-1once a week.Morris water maze,new object recognition,nesting and forced swimming were used to observe the behavioral changes of animals.Lymphocyte subgroups and ROS were measured by Flow cytometry.The cytokines levels were determined by Luminex method.The number of DCX+neurons in brain tissue was observed by immunofluorescence.RESULTS The results showed that AEOL^(-1)0150 could prolong the mean lifespan of SAMR1 mice,but it had no obvious effect on maximal lifespan.What′s more,AEOL^(-1)0150 could significantly improve the spatial learning memory of aged mice,but it could not increase the number of DCX+neurons in the hypothalamic MBH and hippocampal DG regions.Then,we observed the effects of AEOL^(-1)0150 on peripheral blood lymphocyte subgroups and cytokines.We found that AEOL^(-1)0150significantly modulated the lymphocyte subgroups and cytokine release.Especially,AEOL^(-1)0150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-αand IL^(-1)7.CONCLUSION The results indicate that AEOL^(-1)0150 has anti-aging effects,and the effects are closely related to modulating immunity and inhibiting SASP production.

关键词： aging mitochondria-targeted antioxidants SOD mimic SASP endocrine

CA-30,an active fraction derived from Liuwei Dihuang Decoction,ameliorates cognitive deterioration via intestinal microbiome

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第9期33卷 654-655页

作者： ZHOU Wen-xia WANG Jian-hui LEI Xi ZHANG Xiao-rui CHENG Xiao-rui ZHANG Yong-xiang Beijing Institute of Pharmacology and toxicology State Key Laboratory of Toxicology and Medical Countermeasures

Alzheimer disease(AD)is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy.Liuwei Dihuang formula(LW),a classical traditional Chinese medicine(TCM)prescription,has long been used to treat various diseases,including dementia.A great number of pharmacological studies have showed that LW and its active fractions had beneficial effects on AD associated cognitive impairments.Our recent study found that LW,especially its oligosaccharide fraction CA-30,could improve the gastrointestinal microbiota dysbiosis in senescence-accelerated mouse prone 8(SAMP8),an AD mouse model.Here,we sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in SAMP8 mice.Administration with CA-30 decreased the degree of senescence,increased the nest building and locomotor activity,ameliorated the impairments in object recognition,spatial learningand memory behavour,and decreased the active avoidance response in SAMP8 mice.Meanwhile,CA-30 improvedthe cytokine and hormone secretion and lymphocyte subset dysregulation in SAMP8 mice.Moreover,we found that CA-30 altered the abundance of 4 genera and 10 newborn genera.Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment,especially GH85,were also noted.We further found that 7 genera were significantly correlated with the NIM network and cognitive performance.CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels.CA-30 ameliorated the intestinal microbiome,rebalanced the NIM network,improved the AD-like cognitive impairments in SAMP8,and might thus be a potential therapeutic agent for AD.

关键词： Alzheimer disease CA-30 oligosaccharide SAMP8 intestinal microbiome cognition neuroendocrine immunomodulation

The role and mechanism of TRPA1 in paraquat induced pulmonary fibrosis

在线全文

学校读者我要写书评

暂无评论

The role and mechanism of TRPA1 in paraquat induced pulmonar...

A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases

中国毒理学会第九次全国青年科技大会暨第二届生物技术药物...

作者： Weijie Yang Yi Yang Yuan Luo State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology

Paraquat(PQ) is widely used in agricultural production in over 140 countries and regions.PQ selectively gathers in the lung through a saturable absorption,resulting in the highest concentration of PQ in lung tissue among various organs.This accumulation can cause severe inflammation and irreversible pulmonary fibrosis(PF).The mechanism of pulmonary fibrosis is complex,involving oxidative stress,inflammatory response,activation of fibroblasts,secretion of ECM,and participation of multiple cytokines.There are many regulatory factors in the process of PF,and its molecular mechanism is not completely clear.At present,there is no specific drug to treat PQ poisoning.Transient receptor potential A1(TRPA1),a non-selective cation channel protein,is highly expressed in the lung tissue.Due to its permeability towards calcium ions,it has been identified as a toxic receptor in the pulmonary airway and pulmonary vessels.Therefore,we hypothesize that TRPA1 may be a potential key channel protein driving the EMT process in PF,with its elevated levels mediating the influx of calcium ions,which further leads to cell death and tissue damage.Objectives To investigate the role and mechanism of TRPA1 in PQ induced PF,as well as the impact of targeted inhibition of TRPA1 on EMT process and changes in related signaling pathways.Provide research direction for the synthesis of drugs targeting TRPA1 and provide new treatment strategies for improving PQ induced PF.Materials and methods In vitro,we used A549 cells and administered different concentrations of PQ to establish the PF model.We used TRPA1 knockout A549 cells for intervention.CCK8 and cell viability assay were used to detect cell survival.Calcium ion detection reagents was used to detect Ca expression,and patch clamp technology was used to detect Ca channel expression.In terms of molecular validation,Western blot(WB) and Quantitative real-time RT-PCR(qRT-PCR) were used to detect the expression of related proteins and activation of signaling pathways.In vivo,we established the PF mo

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2022年第4期12卷 1652-1661页

作者： Jie Zhou Wei Xu Zezhong Liu Chao Wang Shuai Xia Qiaoshuai Lan Yanxing Cai Shan Su Jing Pu Lixiao Xing Youhua Xie Lu Lu Shibo Jiang Qian Wang key laboratory of medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical Sciences and BSL-3 FacilityShanghai Institute of Infectious Diseases and BiosecurityFudan UniversityShanghai 200032China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging CoVs.We have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory activity.However,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo.Therefore,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of HCoV-OC43.Among these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)tested.The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

关键词： Coronavirus Lipopeptide SARS-CoV-2 Polyethylene glycol Fusion inhibitor

Translocator protein ligand, YL-IPA08, attenuates lipopolysaccharide-induced depression-like behavior by promoting neural regeneration

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2018年第11期13卷 1937-1944页

作者： Xiao-Ying Zhang Li-Ming Zhang Wei-Dong Mi Yun-Feng Li Anesthesia and Operation Center Chinese PLA General Hospital Beijing China State Key Laboratory of Toxicology and Medical Countermeasures Beijing China

Translocator protein has received attention for its involvement in the pathogenesis of depression. This study assessed the effects of the new translocator protein ligand, YL-IPA08, on alleviating inflammation-induced depression-like behavior in mice and investigated its mechanism of action. Mice were intracerebroventricularly injected with 1, 10, 100 or 1000 ng lipopolysaccharide. The tail-suspension test and the forced swimming test confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A mouse model was then established by intraventricular injection of 100 ng lipopolysaccharide. On days 16-24 after model establishment, mice were intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08 effectively reversed the depression-like behavior of lipopolysaccharide-treated mice, restored body mass, increased the number of BrdU-positive cells, and the number and proportion of BrdU and NeuN double-positive cells. These findings indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like behavior in mice by promoting the formation of hippocampal neurons.

关键词： nerve regeneration YL-IPA08 hippocampus dentate gyrus lipopolysaccharide neuroinflammation depression translocator protein neural regeneration

Immunopotentiating activities and TLR4/MAPK related molecular mechanisms research of Lycium barbarum polysaccharide

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2018年第4期32卷 263-264页

作者： Xiao-rui ZHANG Ying-jie LI Chun-hui QI Wen-xia ZHOU Yong-xiang ZHANG State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Beijing China

OBJECTIVE To observe the effect and molecular mechanisms of Lycium barbarum polysaccharide(LBP) and glycopeptides on T,B lymphocytes and macrophages.METHODS ~3H-TdR incorporation method was used to compare the effects of LBP and glycopeptides on the proliferation lymphocytes.Peritoneal macrophages induced by sodium thioglycolate were used to compare the effects of LBP and glycopeptides.T and B lymphocytes were purified by immunomagnetic beads method.Using antibody blocking methods screening polysaccharide activity related receptors.C3H/HeJ mice were further used to observe the activity of LBP.Biolayer interference method was used to observe the binding kinetics of LBP with TLR4 in vitro.TLR4 level was tested by flow cytometry.Western blotting was used to observe the phosphorylation of p-38,SAPK/JNK and ERK.RESULTS The monosaccharide compo.sition of LBP is rhamnose,arabinose and galactose,and does not contain amino acids.The mixed lymphocyte proliferation experiment showed that LBP had more obvious effect on the proliferation of B cells,and glycosides induced T cells proliferation was more obvious.On the purify lymphocytes,it was found that LBP-induced B cells proliferation requires the involvement of macrophages.Further research found that anti-TLR4 antibody had significant inhibitory effect on LBP-induced macrophage release of TNF-α and IL-1β but not the anti-CR3 treatment.C3 H/HeJ mice related results further demonstrated that TLR4 is necessary for LBP activity.Although biolayer interference showed no obvious binding of TLR4/MD2 with LBP,flow cytometry confirmed that LBP could increase TLR4 expression.Western Blot experiments showed that the effect of LBP on macrophage was related to its activation of p-38/MAPK pathway and inhibition of ERK/MAPK and JNK/MAPK pathways.CONCLUSION TLR4 is the activity related receptors of LBP.LBP cannot directly bind to TLR4/MD2 complex in vitro,but can increase TLR4 expression and activate macrophage p-38/MAPK signaling pathway,inhibiting ERK-MAPK and JNK-MAPK signaling pathways.

关键词：枸杞多糖糖肽淋巴细胞治疗方法