摘要：
Parkinson's disease (PD) is a typical neurodegenerative disease and the pathological feature of which is the death of dopamine neurons in the substantia nigra region. At present, neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively studied. The nucleotide-binding oligomerization domain-, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is an inflammatory complex existing in microglia. Its activation promotes the secretion of the inflammatory cytokine interleukin-1beta/18 (IL-1beta/18) and induces pyroptosis, a type of cell death that possesses the potential for inflammation, to rupture microglia to further release IL-1beta. In this review we focus on the mechanisms of activation of the NLRP3 inflammasome and pyroptosis and their inflammatory effects on the development of PD. In addition, we focus on some inhibitors of NLRP3 inflammatory pathways to alleviate the progression of PD by inhibiting central inflammation and provide new therapeutic strategies for the treatment of PD.
作者机构：
[詹济华; 罗林明; 陈乃宏; 裴刚; Qin, Li; 周小江] College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;[罗林明; 陈乃宏; 裴刚; 周小江] Engineering Technology Research Center of Standardization and Function of Traditional Chinese Medicine Decoction Pieces in Hunan Province, Changsha 410208, China;[陈乃宏] Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
通讯机构：
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
摘要：
OBJECTIVE:To investigate the antidepressant-like effect of active fraction of Polyrhachis vicina Roger (AFPR) in a rat depression model,and to elucidate the underlying mechanism.METHODS:AFPR was extracted with ethanol followed by petroleum ether.Its antidepressant-like effect was investigated in mice by tail suspension test (TST),forced swimming test (FST) and open field test (OPT).A repeated dose of reserpine (0.5 mg/kg,daily for 14 d) was used to establish a rat depression model.Fluoxetine was used as positive control agent.The effect of AFPR on reserpine-induced ptosis,hypothermia and akinesia,the levels of monoamines and their metabolites,and the activity of monoamine oxidase (MAO) in hippocampus and prefrontal cortex were determined.RESULTS:Administration of AFPR by gavage at 160 and 320 mg/kg significantly reduced the duration of immobility in the FST and TST,and did not affect locomotor activity in the OPT.In the reserpine-induced depression model,AFPR attenuated anhedonia,demonstrated by reversing hypothermia,akinesia and sucrose consumption.AFPR significantly increased the concentration of monoamines,including dopamine,serotonin,noradrenaline and acetylcholine.CONCLUSION:AFPR normalized the metabolism rates of noradrenaline,serotonin and dopamine,and the activity of MAO,which were altered by chronic reserpine exposure.The findings suggest that modulation of the monoaminergic neurotransmitter system likely underlies the antidepressant-like effect of AFPR.
摘要：
Major depressive disorder (MDD) remains a major public health problem worldwide. The association between MDD and the dysfunction of gap junction channels (GJCs) in glial cells, especially astrocytes, is still controversial. This review provides an overview of the role of astrocyte GJCs in LMDD. Exposure to chronic unpredictable stress caused a reduction in connexin expression in the rat prefrontal cortex, a result that is consistent with clinical findings reported in postmortem studies of brains from MDD patients. Chronic antidepressant treatment in these rats increased the expression of connexins. However, pharmacological GJC blockade in normal rodents decreased connexin expression and caused depressive-like behaviors. Furthermore, GJC dysfunction affects electrical conductance, metabolic coupling and secondary messengers, and inflammatory responses, which are consistent with current hypotheses on MDD. All these results provide a comprehensive overview of the neurobiology of MDD. This review supports the hypothesis that the regulation of GJCs between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants.
作者：
AI Qi-di;CHEN Chen;CHU Shi-feng;ZHANG Zhao;LUO Yun;...
期刊：
中国药理学与毒理学杂志,2018年(9):675-676 ISSN：1000-3002
作者机构：
Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces &Colege of Pharmacy,Hunan University of Chinese Medicine;State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica &Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College;Key Laboratory of Human Disease Comparative Medicine,NHFPC,Institute of Laboratory Animal Science,Peking Union Medicine College and Chinese Academy of Medical Sciences
摘要：
OBJECTIVE To investigate the effects of IMM-H004 on permanent focal cerebral ischemia injury and associated cardiopulmonary complications,further elucidating the molecular mechanisms.METHODS The effects of IMM-H004 were investigated in wild-type(WT) and CKLF1-/-rats.The effects of IMM-H004 on ischemic stroke injury and its cardiopulmonary complications were determined using 2,3,5-triphenyltetrazolium chloride(TTC) staining,behavior tests,magnetic resonance imaging(MRI)scans,enzyme-linked immunosorbent assay(ELISA),Nissl staining,and histo-pathological examination.Multiple molecular experiments including immunohistological staining,immunofluorescence staining,quantitative RT-PCR,Western blotting,and co-immunoprecipitation assays were used to elucidate the underlying mechanisms.RESULTS IMM-H004 treatment provided significant protection against ischemic stroke-induced brain injury and associated cardiopulmonary complications,through CKLF1-depedent-anti-inflammation pathway in rats.IMM-H004 downregulated the amount of CKLF1 and disturbed the combination between CKLF1 and C-C chemokine receptor type 4,suppressing the inflammatory response and protecting the damaged organs in ischemic setting.CONCLUSION This preclinical study established efficacy of IMM-H004 as a potential therapeutic medicine for ischemic stroke and associated cardiopulmonary complications.The protective effects of IMM-H004 may due to its specific mechanism through CKLF1.These results support further efforts to develop IMM-H004 for human clinical trials in acute cerebral ischemia,especially for patients who are not suitable for reperfusion therapy.
作者机构：
[Yang, Peng-Fei; Feng, Xiao-Ye; Song, Xiu-Yun; Chen, Nai-Hong; Liu, Dan-Dan; Wang, Ying-Ying] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China.;[Yang, Peng-Fei; Feng, Xiao-Ye; Song, Xiu-Yun; Chen, Nai-Hong; Liu, Dan-Dan; Wang, Ying-Ying] Chinese Acad Med Sci, Neurosci Ctr, Beijing 100050, Peoples R China.;[Yang, Peng-Fei; Feng, Xiao-Ye; Song, Xiu-Yun; Chen, Nai-Hong; Liu, Dan-Dan; Wang, Ying-Ying] Peking Union Med Coll, 2 Nanwei Rd, Beijing 100050, Peoples R China.;[He, Xin; Liu, Dan-Dan] Tianjin Univ Tradit Chinese Med, Tianjin 300193, Peoples R China.;[Ai, Qi-Di; Chen, Nai-Hong] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Chen, Nai-Hong] P;[Chen, Nai-Hong] C;Peking Union Med Coll, 2 Nanwei Rd, Beijing 100050, Peoples R China.;Chinese Acad Med Sci, Inst Mat Med, 2 Nanwei Rd, Beijing 100050, Peoples R China.
关键词：
Chemokine like factor 1;C19 peptide;C27 peptide;CCR4;Allergic diseases;Autoimmune diseases
摘要：
Currently, the research of chemokines has penetrated into many fields of life science. A new kind of chemokines, chemokine like factor 1 (CKLF1), which is cloned through suppression subtractive hybridisation (SSH) technology is expressed widely in human body, especially in the lung and peripheral blood leukocytes. CKLF1 has a broad spectrum of chemotaxic activity for many cells, such as lymphocytes, macrophages, bone marrow cells, nerve cells and so on. In addition, CKLF1 also stimulates the regeneration of skeletal muscle cells in vivo. Collecting data derived from our and other laboratories show that CKLF1 has an important relationship with allergic diseases, autoimmune diseases, tumors, cardio-cerebrovascular diseases and so on. Therefore, there be an important theoretical purport and applied value to make a summary of pharmacological progress of CKLF1.
