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Comprehensive Bibliometric Analysis of the kynurenine pathway in Mood Disorders:Focus on Gut Microbiota Research

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Comprehensive Bibliometric Analysis of the Kynurenine Pathwa...

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter

2022第27届广东省药师周大会

作者： Xiuqing Zhu Jinqing Hu Shuhua Deng Yaqian Tan Chang Qiu Ming Zhang Xiaojia Ni Haoyang Lu Zhanzhang Wang Lu Li Yayan Luo Shanqing Huang Tao Xiao Shujing Liu Xiaolin Li Dewei Shang Yuguan Wen Department of Pharmacy The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital) Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders GuangzhouChina 3Institute of NeuropsychiatryThe Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital)

Background:Emerging evidence implicates the dysregulated kynurenine pathway(KP),an immune-inflammatory pathway,in the pathophysiology of mood disorders(MD),including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory *** metabolites of the KP,an important part of the microbiota-gut-brain axis,serve as immune system modulators linking the gut microbiota(GM) with the host central nervous ***:This bibliometric analysis aimed to provide a first glimpse into the KP in MD,with a focus on GMresearch in this field,toguide future researchand promote the development of this ***:Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection(WoSCC),and analyzed in CiteSpace(5.7 R5 W),biblioshiny(using R-Studio),and VOSviewer(1.6.16).Results:In total,1,064 and 948 documents were extracted from the Scopus and WoSCC databases,*** publications have shown rapid growth since 2006,partly owing to the largest research hotspot appearing since then,"quinolinic acid." All the top five most relevant journals were in the neuropsychiatry field,such as Brain Behavior and *** USA and Innsbruck Medical University were the most influential country and institute,*** co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry *** co-citation analysis revealed that the top four most important research focuses were "kynurenine pathway,""psychoneuroimmunology," "indoleamine2,3-dioxygenase," and "proinflammatory cytokines,"and the most recent focuswas "gut-brain axis," thus indicating the role of the KP in bridgingthe GM and the host immune system,and togetherreflecting the field’s research *** analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics "Alzheimer’s disease," "prefrontal cortex," and "acid," were research frontiers

关键词： kynurenine pathway mood disorders depression bipolar disorder bibliometric analysis gut microbiota microbiota-gut-brain axis immune system

来源： cnki会议评论

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Chinese Journal of Integrative Medicine 2022年第7期28卷 586-593页

作者： JIANG Bing WU Ruo-ming LI Hai-dong LI Kun LI Hui DANG Wen-zhen FENG Gui-ze BAO Wei-lian YE Guan SHEN Xiao-yan Department of Pharmacology School of PharmacyFudan UniversityShanghai 200120China Department of Pharmacology of Chinese Materia Medica School of Traditional Chinese MedicineGuangdong Pharmaceutical UniversityGuangzhou 510006China Central Research Institute Shanghai Pharmaceuticals Holding Co.Ltd.Shanghai 200120China

Objective: To investigate the therapeutic effect of Yixin Ningshen Tablet(YXNS) on comorbidity of myocardial infarction(MI) and depression in rats and explore the underlying mechanism. Methods: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights,including control, model, fluoxetine(FLXT, 10 mg/kg), low-dose YXNS(LYXNS, 100 mg/kg), and high-dose YXNS(HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction(MI) area and myocardial apoptosis was also detected. Serum levels of interleukin(IL)-6, IL-1β, tumor necrosis factor-α(TNF-α), 5-hydroxytryptamine(5-HT), adrenocorticotrophic hormone(ACTH), corticosterone(CORT), and norepinephrine(NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5’-monophosphate-activated protein kinase(AMPK), p-AMPK,peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and nuclear respiratory factor 1(NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase(IDO1), kynurenine 3-monooxygenase(KMO), and kynureninase(KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. Results: Compared with the model group,the cardiac function of rats treated with YXNS significantly improved(P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats(P<0.01 or P<0.05), promoted AMPK phosphorylation,and increased PGC-1α protein expression(P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH,and CORT(all P<0.05). More

关键词： Yixin Ningshen Tablet depression cardiovascular disorders inflammatory factor monoamine neurotransmitter kynurenine pathway Chinese medicine

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis

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Neural Regeneration Research 2017年第8期12卷 1262-1267页

作者： Rebecca M.Heidker Mitchell R.Emerson Steven M.Le Vine Department of Molecular and Integrative Physiology University of Kansas Medical Center Department of Pharmaceutical Sciences College of Pharmacy-Glendale Midwestern University

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth： insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

关键词： acetyl-coenzyme A carboxylase biotin estrogen iron kynurenine pathway mitochondria thyroidhormone remyelination stem cells vitamin D

Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage

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Acta Pharmaceutica Sinica B 2021年第3期11卷 763-780页

作者： Di Wang Danting Li Yuxin Zhang Jie Chen Ying Zhang Chuyao Liao Siyuan Qin Yuan Tian Zunjian Zhang Fengguo Xu Key Laboratory of Drug Quality Control and Pharmacovigilance(Ministry of Education) State Key Laboratory of Natural MedicineChina Pharmaceutical UniversityNanjing 210009China Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan(Trp)àkynurenine(KYN)àkynurenic acid(KA) axis metabolism. Mechanistically,chemotherapy-induced intestinal damage triggered the formation of an interleukin-6(IL-6)àindoleamine2,3-dioxygenase 1(IDO1)àaryl hydrocarbon receptor(AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35(GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity in vivo suggests that chemotherapeutics combined with the two could be a promising therapeutic strategy for cancer patients in *** work highlights GPR35 and AHR as the guardian of kynurenine pathway metabolism and core component of defense responses against intestinal damage.

关键词： Intestinal toxicity kynurenine pathway Gradually sensing AHR GPR35