|
|
|
| Discussion on the molecular mechanism of genistein therapy for depression based on network pharmacology#br# |
| HU Yanzhen1 ZHANG Yuanyuan1 HUANG Bin1 WANG Yamin1 CHEN Le1▲ YANG Zhi2 |
1.Institute of Chinese Materia Medica, Jiangxi Provincial Institute of Traditional Chinese Medicine, Jiangxi Province, Nanchang 330046, China;
2.Department of Neonatal Surgery, Jiangxi Provincial Children’s Hospital, Jiangxi Province, Nanchang 330006, China |
|
|
|
Abstract Objective To systematically explore the key targets and molecular mechanisms of genistein in the treatment of depression based on network pharmacology. Methods The traditional Chinese medicine systems pharmacology database and analysis platform, comparative toxicogenomics, TTD, GeneCards, Home-NCBI-Gene and other databases were used to obtain the related targets of genistein in the treatment of depression. Protein-protein interaction (PPI) and “component-target-disease” network diagrams were constructed, and key targets were screened according to PPI interaction network diagrams. DAVID database was used to analyze the GO and KEGG pathways of target protein genes. Results Six key targets including MAPK1, PTGS2, MMP9, VEGFA, AKT1 and TNF, were identified by screening. A total of 33 GO functional information were obtained, including positive regulation of cell division, protein kinase B signal transduction, positive regulation of serine peptide phosphorylation, positive and negative regulation of RNA polymerase Ⅱ promoter transcription, immune response, positive regulation of MAP kinase activity, positive regulation of cell proliferation, blood glucose homeostasis, angiogenesis, positive regulation of NF-κB signal, etc. KEGG pathway enrichment analysis screened 23 signaling pathways, mainly involving cancer, immune inflammatory response, apoptosis, viral infection, etc. Conclusion Genistein has “multi-target-multi-pathway” regulation in the treatment of depression. This study provides a new idea for the molecular mechanism verification of genistein’s anti-depression.
|
|
|
|
|
|
[1] Autry AE，Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders [J]. Pharmacol Rev，2012， 64（2）：238-258.
[2] Zhu XL，Chen JJ，Han F，et al. Novel antidepressant effects of Paeonol alleviate neuronal injury with concomitant alterations in BDNF，Rac1 and RhoA levels in chronic unpredictable mild stress rats [J]. Psychopharmacology，2018， 235（7）：2177-2191.
[3] 张兆英.围绝经期抑郁症从心肾论治探析[J].陕西中医，2019，40（11）：1611-1615.
[4] Ferrari AJ，Stockings E，Khoo JP，et al. The prevalence and burden of bipolar disorder：findings from the Global Burden of Disease Study 2013 [J]. Bipolar Disord，2016，18（5）：440-450.
[5] 王爱玲，鞠雪涛，石紫云.超声在绝经后激素补充治疗评估中的临床价值[J].陕西医学杂志，2006（10）：1272-1273.
[6] Atteritano M，Mazzaferro S，Bitto A，et al. Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women：a 2-year randomized，double-blind，controlled study [J]. Osteoporos Int，2014，25（3）：1123-1129.
[7] Bing ZT，Cheng ZY，Shi DF，et al. Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology [J]. BMC Complement Altern Med，2018，18（1）：293.
[8] 朱华英，谢红仙.围绝经期抑郁症与雌激素及单胺类递质水平的相关性研究[J].中国妇幼健康研究，2014，25（6）：969-970，1004.
[9] Xiao YZ，Liu H，Yu JJ，et al. MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy [J]. Autophagy，2016，12（3）：592-593.
[10] Chiara F，Concetta C，Raffaella C，et al. Neuroplasticity and second messenger pathways in antidepressant efficacy：pharmacogenetic results from a prospective trial investigating treatment resistance [J]. Eur Arch Psychiatry Clin Neurosci，2017，267（8）：723-735.
[11] Ditzen C，Tang N，Jastroff AM，et al. Cerebrospinal fluid biomarkers for major depression confirm relevance of associated pathophysiology [J]. Neuropsychopharmacology，2012，37（4）：1013-1025.
[12] Hellmann J，Tang Y，Zhang MJ，et al. Atf3 negatively regulates Ptgs2/Cox2 expression during acute inflammation [J]. Prostag Oth Lipid M，2015：116-117.
[13] Zunszain PA，Hepgul N，Pariante CM. Infammation and epression [M] //Cowen PJ，Sharp T，Lau JYF（eds）. Behavioral neurobiology of depression and its treatment. erlin：Springer-Verlag Berlin Heidelberg，2013：135-151.
[14] Leung DW，Cachianes G，Kuang WJ，et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science，1989，246（4935）：1306-1309.
[15] De Rossi P，Harde E，Dupuis JP，et al. A critical role for VEGF and VEGF2 in NMDA receptor synaptic function and fear-related behavior [J]. Mol Psychiatry，2016，21（12）：1768-1780.
[16] 李剑虹，王磊，张克让，等.AKT1基因多态性与重性抑郁障碍认知功能的关联分析[J].中国药物与临床，2011， 11（10）：1116-1118.
[17] 马柯，张洪秀，王广燕，等.TNF-α在抑郁症中的作用和机制研究[J].生命科学，2015，27（5）：574-581.
[18] Dowlati Y，Herrrmann N，Swardfager W，et al. A meta-analysis of cytokines in major depression [J]. Biol Psychiatry，2010，67（5）：446-457.
[19] 刘玉芝，寇海燕.肿瘤坏死因子-α基因多态性与首发抑郁症及舍曲林疗效的关联研究[J].中国当代医药，2020， 27（26）：17-23.
[20] Girotti M，Donegan JJ，Morilak DA. Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain [J]. Psychoneuroendocrinology，2011，36（8）：1164-1174.
[21] Duan L，Zhang XD，Miao WY，et al. PDGFRβ cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2 [J]. Neuron，2018，100（1）：183-200.
[22] 陆梅娟，莫亚莉.抑郁症患者血清TNF-α、IL-8、ICAM-1、NF-κB水平及其意义[J].中国现代医学杂志，2018， 28（32）：117-120.
[23] 刘丽珠，刘薇，樊琳，等.黄芪多糖对大鼠脑卒中后抑郁的影响[J].中国医药导报，2019，16（7）：11-14.
[24] 覃斌，叶刚，吴述轩，等.氯胺酮通过抑制ERK1/2/NF-κB信号通路发挥抗抑郁作用[J].神经损伤与功能重建，2020，15（3）：134-137.
[25] 张世娇，王娜梅，王慧霞.逍遥合剂对产后抑郁症模型大鼠行为学、神经递质及ERK1/2通路影响的研究[J].陕西中医，2018，39（12）：1663-1666. |
|
|
|
