Skip to content
2000
Volume 21, Issue 15
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Paeoniflorin has been proven to have neuroprotective and antidepressant effects in several studies. However, there is currently no comprehensive elaboration of its antidepressant effects through network pharmacology combined with transcriptomics analysis. The purpose of this study is to explore the potential mechanisms by which paeoniflorin exerts its antidepressant effects using network pharmacology and transcriptomics sequencing approaches.

Methods

We utilized metascape to enrich the intersecting targets for paeoniflorin and depression for enrichment analyses. Additionally, we employed Cytoscape software to construct target pathway networks. For the screening of differentially expressed genes (DEGs) altered by paeoniflorin, we sequenced mRNA from the hippocampal tissue of CUMS model mice using the BMKCloud platform. We further enriched their biological functions and signaling pathways by using the Omishare database. The study utilized a combination of network pharmacology and transcriptomics analysis to evaluate the interactions between paeoniflorin and key targets. The results were then verified through a molecular docking process and a subsequent Western blot experiment.

Results

According to a comprehensive analysis, paeoniflorin has 19 key targets that are closely related to its therapeutic effect. Molecular docking revealed that paeoniflorin has a high affinity for HIF-1α, VEGFA, and other targets. Furthermore, protein expression and immunofluorescence staining analysis showed that paeoniflorin significantly increased the expression level of HIF-1α and VEGFA in the hippocampus of depression model mice.

Conclusion

These findings suggest that paeoniflorin may have therapeutic potential in depression through the activation of the HIF-1α-VEGFA pathway.

Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808269296231019055844
2023-10-27
2025-07-08
Loading full text...

Full text loading...

References

  1. GoldsteinZ. RosenB. HowlettA. AndersonM. HermanD. Interventions for paternal perinatal depression: A systematic review.J. Affect. Disord.202026550551010.1016/j.jad.2019.12.029 32090778
    [Google Scholar]
  2. Van NielM.S. PayneJ.L. Perinatal depression: A review.Cleve. Clin. J. Med.202087527327710.3949/ccjm.87a.19054 32357982
    [Google Scholar]
  3. CaoC. HeX. WangW. ZhangL. LinH. DuL. Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia-reperfusion rats after intravenous administration ofPaeoniae Radix extract.Biomed. Chromatogr.200620121283128810.1002/bmc.658 17006964
    [Google Scholar]
  4. JiangZ. ChenJ. ChenJ. LeiZ. ChenH. WuJ. BaiX. WanyanP. YuQ. Anti-inflammatory effects of paeoniflorin caused by regulation of the hif1a/miR-210/caspase1/GSDMD signaling pathway in astrocytes: A novel strategy for hypoxia-induced brain injury in rats.Immunopharmacol. Immunotoxicol.202143441041810.1080/08923973.2021.1924194 34114917
    [Google Scholar]
  5. GuoK. ZhangY. LiL. ZhangJ. RongH. LiuD. WangJ. JinM. LuoN. ZhangX. Neuroprotective effect of paeoniflorin in the mouse model of Parkinson’s disease through α-synuclein/protein kinase C δ subtype signaling pathway.Neuroreport202132171379138710.1097/WNR.0000000000001739 34718250
    [Google Scholar]
  6. LiY. ZhengX. XiaS. LiY. DengH. WangX. ChenY. YueY. HeJ. CaoY. Paeoniflorin ameliorates depressive-like behavior in prenatally stressed offspring by restoring the HPA axis- and glucocorticoid receptor- associated dysfunction.J. Affect. Disord.202027447148110.1016/j.jad.2020.05.078 32663978
    [Google Scholar]
  7. ChengJ. ChenM. WanH.Q. ChenX.Q. LiC.F. ZhuJ.X. LiuQ. XuG.H. YiL.T. Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation.J. Ethnopharmacol.202127411404610.1016/j.jep.2021.114046 33753146
    [Google Scholar]
  8. TianD.D. WangM. LiuA. GaoM.R. QiuC. YuW. WangW.J. ZhangK. YangL. JiaY.Y. YangC.B. WuY.M. Antidepressant Effect of Paeoniflorin Is Through Inhibiting Pyroptosis CASP-11/GSDMD Pathway.Mol. Neurobiol.202158276177610.1007/s12035‑020‑02144‑5 33025508
    [Google Scholar]
  9. ZhouY. WangM. YanS. KongJ. XieP. Paeoniflorin prevents depression like behavior in rats by suppressing mitophagy mediated nod like receptor protein 3 inflammasome signaling.Pharmacogn. Mag.2021177432733310.4103/pm.pm_85_20
    [Google Scholar]
  10. MaoQ.Q. ZhongX.M. QiuF.M. LiZ.Y. HuangZ. Protective effects of paeoniflorin against corticosterone-induced neurotoxicity in PC12 cells.Phytother. Res.201226796997310.1002/ptr.3673 22131171
    [Google Scholar]
  11. ZhongX. LiG. QiuF. HuangZ. Paeoniflorin Ameliorates Chronic Stress-Induced Depression-Like Behaviors and Neuronal Damages in Rats via Activation of the ERK-CREB Pathway.Front. Psychiatry2019977210.3389/fpsyt.2018.00772 30692946
    [Google Scholar]
  12. HongC. CaoJ. WuC.F. KadiogluO. SchufflerA. KauhlU. KlauckS.M. OpatzT. ThinesE. PaulN.W. EfferthT. The Chinese herbal formula Free and Easy Wanderer ameliorates oxidative stress through KEAP1-NRF2/HO-1 pathway.Sci Rep-Uk20177
    [Google Scholar]
  13. ChenJ. ZhuW. ZengX. YangK. PengH. HuL. Paeoniflorin exhibits antidepressant activity in rats with postpartum depression via the TSPO and BDNF mTOR pathways.Acta Neurobiol. Exp. (Warsz.)202282334735710.55782/ane‑2022‑033 36214717
    [Google Scholar]
  14. YuanH. MaQ. CuiH. LiuG. ZhaoX. LiW. PiaoG. How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?Molecules2017227113510.3390/molecules22071135 28686181
    [Google Scholar]
  15. YangX. KuiL. TangM. LiD. WeiK. ChenW. MiaoJ. DongY. High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery.Front. Genet.2020111910.3389/fgene.2020.00019 32117438
    [Google Scholar]
  16. ChengM. LiT. HuE. YanQ. LiH. WangY. LuoJ. TangT. A novel strategy of integrating network pharmacology and transcriptome reveals antiapoptotic mechanisms of Buyang Huanwu Decoction in treating intracerebral hemorrhage.J. Ethnopharmacol.2023319Pt 1117123
    [Google Scholar]
  17. ZhangW. SangS. PengC. LiG.Q. OuL. FengZ. ZouY. YuanY. YaoM. Network Pharmacology and Transcriptomic Sequencing Analyses Reveal the Molecular Mechanism of Sanguisorba officinalis Against Colorectal Cancer.Front. Oncol.202212807718
    [Google Scholar]
  18. KongJ. SunS. MinF. HuX. ZhangY. ChengY.A-O. LiH. WangX. LiuX. Integrating Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Hydroxysafflor Yellow A in Delaying Liver Aging.Int. J. Mol. Sci.202223221428110.3390/ijms232214281
    [Google Scholar]
  19. LiuZ. SunY. ZhenH. NieC. Network Pharmacology Integrated with Transcriptomics Deciphered the Potential Mechanism of Codonopsis pilosula against Hepatocellular Carcinoma.Evid. Based Complement. Alternat. Med.202220221340194
    [Google Scholar]
  20. ChemSourceProfessional chemical search engine.Available From: https://www.chemsrc.com/
  21. ChemSourceExplore Chemistry.Available From: https://pubchem.ncbi.nlm.nih.gov/
  22. SIBSwissTargetPrediction.Available From: http://www.swisstargetprediction.ch/ 2019
  23. Comparative Toxicogenomics DatabaseIlluminating how chemicals affect human health.Available From: https://ctdbase.org/ 2023
  24. GeneCards®The Human Gene Database.Available From: https://www.genecards.org 2023
  25. SafranM. DalahI. AlexanderJ. RosenN. Iny SteinT. ShmoishM. NativN. BahirI. DonigerT. KrugH. Sirota-MadiA. OlenderT. GolanY. StelzerG. HarelA. LancetD. GeneCards Version 3: The human gene integrator.Database (Oxford)201020100baq02010.1093/database/baq020 20689021
    [Google Scholar]
  26. OMIMAn Online Catalog of Human Genes and Genetic Disorders.Available From: https://www.omim.org 2023
  27. HamoshA. AmbergerJ.S. BocchiniC. ScottA.F. RasmussenS.A. Online Mendelian Inheritance in Man (OMIM ®): Victor MCKUSICK 's magnum opus.Am. J. Med. Genet. A.2021185113259326510.1002/ajmg.a.62407 34169650
    [Google Scholar]
  28. DrugBankBuilding the foundation for better health outcomes.Available From: https://go.drugbank.com/ 2023
  29. Venny.Available From: https://bioinfogp. cnb.csic.es/tools/venny/index.html/ 2007
  30. UniProtAvailable From: http:ww.uniprot.org/
  31. STRINGWelcome to STRING.Available From: https://string-db.org/ 2023
  32. MetascapeMultiple Gene List.Available From: https://metascape.org/ 2023
  33. Bioinformatics.Available From: http://www.bioinformatics.com.cn/login/
  34. SunX. ZhangT. ZhaoY. CaiE. ZhuH. LiuS. Panaxynol attenuates CUMS-induced anxiety and depressive-like behaviors via regulating neurotransmitters, synapses and the HPA axis in mice.Food Funct.20201121235124410.1039/C9FO03104A 32048672
    [Google Scholar]
  35. LiJ. HuangS. HuangW. WangW. WenG. GaoL. FuX. WangM. LiangW. KwanH.Y. ZhaoX. LvZ. Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice.Oncotarget2017858264828210.18632/oncotarget.14160 28030814
    [Google Scholar]
  36. BMKCloudEukaryotes have platforms for transcriptome analysis of reference genomes.Available From: https://international.biocloud.net/ 2023
  37. RCSB Protein Data Bank. RCSB Protein Data Bank (RCSB PDB). 2023. Available From: https://www.rcsb.org/pdb/home/home.do
  38. TingE.Y.C. YangA.C. TsaiS.J. Role of Interleukin-6 in Depressive Disorder.Int. J. Mol. Sci.2020216219410.3390/ijms21062194 32235786
    [Google Scholar]
  39. NuttD.J. Relationship of neurotransmitters to the symptoms of major depressive disorder.J. Clin. Psychiatry200869Suppl. E147 18494537
    [Google Scholar]
  40. KoenigH.G. Depression in the medically ill: A common and serious disorder.Int. J. Psychiatry Med.2008304295297
    [Google Scholar]
  41. ZhangZ. DengT. WuM. ZhuA. ZhuG. Botanicals as modulators of depression and mechanisms involved.Chin. Med.20191424
    [Google Scholar]
  42. WangY. ZhangF. LiX. LiX. WangJ. HeJ. WuX. ChenS. ZhangY. A.-O. LiY. A.-O.
  43. WuW. ZhangZ. LiF. DengY. LeiM.A-O. LongH. HouJ. WuW. A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease.Int. J. Mol. Sci.2020215176610.3390/ijms21051766
    [Google Scholar]
  44. KumarS.A-O. ShihC.M. TsaiL.A-O. DubeyR.A-O. GuptaD. ChakrabortyT. SharmaN. SinghA.V. SwarupV.A-O. SinghH.A-O. Transcriptomic Profiling Unravels Novel Deregulated Gene Signatures Associated with Acute Myocardial Infarction: A Bioinformatics Approach.Genes (Basel).20221312212310.3390/genes13122321
    [Google Scholar]
  45. XieZ. HuangS. XieS. ZhouW. LiC. XingZ. WangZ. WuZ. LiM. Potential Correlation Between Depression-like Behavior and the Mitogen-Activated Protein Kinase Pathway in the Rat Hippocampus Following Spinal Cord Injury.World Neurosurg.2021154e29e3810.1016/j.wneu.2021.06.093 34271150
    [Google Scholar]
  46. ZhangS. JiangM. YanS. LiangM. WangW. YuanB. XuQ. Network Pharmacology-Based and Experimental Identification of the Effects of Paeoniflorin on Major Depressive Disorder.Front. Pharmacol.20221279301210.3389/fphar.2021.793012 35185541
    [Google Scholar]
  47. GaoF. YangS. WangJ. ZhuG. cAMP-PKA cascade: An outdated topic for depression?Biomed. Pharmacother.202215011303010.1016/j.biopha.2022.113030 35486973
    [Google Scholar]
  48. ZhaoD. ZhangJ. WangX. Effects of paeoniflorin and paeoniflorin on hippocampal monoamine neurotransmitters, cAMP, and cGMP in rats with chronic restraint stress and liver depression.World Traditional Chinese Medicine20181301146150
    [Google Scholar]
  49. ShimJ. MadsenJ. VEGF Signaling in Neurological Disorders.Int. J. Mol. Sci.201819127510.3390/ijms19010275 29342116
    [Google Scholar]
  50. KaelinW.G.Jr RatcliffeP.J. Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway.Mol. Cell200830439340210.1016/j.molcel.2008.04.009 18498744
    [Google Scholar]
  51. KangI. KondoD. KimJ. LyooI.K. Yurgelun-ToddD. HwangJ. RenshawP.F. Elevating the level of hypoxia inducible factor may be a new potential target for the treatment of depression.Med. Hypotheses202114611039810.1016/j.mehy.2020.110398 33246695
    [Google Scholar]
  52. HaratizadehS. RanjbarM. BasiriM. NozariM. Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism.J. Chem. Neuroanat.202313010225710.1016/j.jchemneu.2023.102257 36918074
    [Google Scholar]
  53. DeyamaS. BangE. WohlebE.S. LiX.Y. KatoT. GerhardD.M. DutheilS. DwyerJ.M. TaylorS.R. PicciottoM.R. DumanR.S. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine.Am. J. Psychiatry2019176538840010.1176/appi.ajp.2018.17121368 30606046
    [Google Scholar]
  54. LiG. ZhaoM. ChengX. ZhaoT. FengZ. ZhaoY. FanM. ZhuL. FG-4592 Improves Depressive-Like Behaviors through HIF-1-Mediated Neurogenesis and Synapse Plasticity in Rats.Neurotherapeutics202017266467510.1007/s13311‑019‑00807‑3 31820273
    [Google Scholar]
/content/journals/lddd/10.2174/0115701808269296231019055844
Loading
/content/journals/lddd/10.2174/0115701808269296231019055844
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test