Skip to content
2000
Volume 28, Issue 3
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

As a Chinese medicinal formula, the Jianshen Lishui prescription has been clinically proven to be effective in treating intracerebral hemorrhage (ICH). Yet, the mechanisms involved are unknown.

Methods

: It involved the screening of active components in the Jianshen Lishui prescription, identification of potential targets for these components, and the screening of ICH-related targets. Common targets for both disease and drug were identified. Protein-protein interaction networks were constructed, followed by further screening of core targets. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on these core targets. Finally, molecular docking verification was carried out using the active components and core targets. : It was conducted using a rat model of intracerebral hemorrhage. This involved observing neurological deficit scores in the rats and measuring cerebral water content. The effects of Jianshen Lishui prescription on the neurological function, cerebral water content, and brain tissue core targets were observed through HE staining, Western blot and qPCR.

Results

(1) In this study, 29 common targets were obtained by intersecting 256 potential drug targets and 642 genes associated with ICH. 9 core targets were obtained by employing the protein-protein interaction (PPI) construction system to screen more specific targets. In addition, the findings revealed that the molecular mechanism of Jianshen Lishui prescription in treating ICH was mainly related to cancer signaling pathways and signal transduction pathways, based on the results of GO and KEGG enrichment analysis. Molecular docking results showed that the active constituent of Jianshen Lishui prescription mannitol has the highest binding activity with KRAS, luteolin, and Poria sterol with AR, INS1 and KRAS, cerebrosterol with GNB1, INS 1 and ESR1, and sitosterol with AR, INS1 and KRAS. (2) Animal experiments verified that Jianshen Lishui prescription significantly alleviated encephaledema and improved nerve functions of the rat model of ICH. And INS1 expression levels were upregulated and the expression levels of AR, KRAS, PTGS2, and ESR1 were down-regulated by the prescription.

Conclusion

Jianshen Lishui prescription protects the nerve function of ICH patients by inhibiting inflammation and reducing cerebral edema. This study provides more supportive evidences for the clinical use of traditional Chinese prescriptions in ICH treatment.

Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073256436231031100059
2024-01-11
2025-04-02
Loading full text...

Full text loading...

References

  1. GrossB.A. JankowitzB.T. FriedlanderRM. Cerebral Intraparenchymal Hemorrhage: A Review.JAMA2019321131295130310.1001/jama.2019.2413, 30938800
    [Google Scholar]
  2. JenniferR.M. ArvindB.B. ElizabethG.M. KristenB.S. ChristopherJ.F. AnjailZ.S. RitvijB. WamdaO.A. JonE.T. CharlesC.M. SteveW. BabarA.K. LouiseD.M. SeanI.S. FarhaanS.V. High in-hospital blood pressure variability and severe disability or death in primary intracerebral hemorrhage patients.Int. J. Stroke201914998799510.1177/1747493019827763, 30681042
    [Google Scholar]
  3. PetraS. RobertD.B. MiroslavZ. PavlaK. TomasB. TomášK. ViktorW. OndřejV. JosefB. RobertM. Incidence of Hospitalized Stroke in the Czech Republic: The National Registry of Hospitalized Patients.J. Stroke Cerebrovasc. Dis.201726597998610.1016/j.jstrokecerebrovasdis.2016.11.006,27955808
    [Google Scholar]
  4. Chinese Society of Neurology, Chinese Stroke Society. Guidelines for the diagnosis and treatment of cerebral hemorrhage in China (2019).Chinese Journal of. Neurology201952129941006
    [Google Scholar]
  5. WangW-J. LuJ-J. WangY-J. WangC-X. WangY-L. KolinH. YangZ-H. LiuL. WangA-X. ZhaoX-Q. China National Stroke Registry (CNSR). Clinical characteristics, management, and functional outcomes in Chinese patients within the first year after intracerebral hemorrhage: analysis from China National Stroke Registry.CNS Neurosci. Ther.201218977378010.1111/j.1755‑5949.2012.00367.x,22943144
    [Google Scholar]
  6. DuanT. LiL. YuY-J. LiT-T. HanR. SunX-Y. CuiY. LiuT. WangX-Y. WangY. FanX. LiuY. ZhangH. Traditional Chinese medicine use in the pathophysiological processes of intracerebral hemorrhage and comparison with conventional therapy.Pharmacol. Res.202217910620010.1016/j.phrs.2022.106200,35367344
    [Google Scholar]
  7. XuS-Y. PangQ-Y. LinZ-X. ZhangN. Effect of integrated traditional Chinese and Western medicine therapy for acute hypertensive intracerebral hemorrhage: a meta-analysis.Artif. Cells Nanomed. Biotechnol.20174561610.1080/21691401.2016.1215327,27570142
    [Google Scholar]
  8. LiX. HuangX. TangY-T. ZhaoF-L. CaoY-M. Yin,l.; Li,G-C. Assessing the Pharmacological and Therapeutic Efficacy of Traditional Chinese Medicine Liangxue Tongyu Prescription for Intracerebral Hemorrhagic Stroke in Neurological Disease Models.Front. Pharmacol.20189116910.3389/fphar.2018.01169,30459599
    [Google Scholar]
  9. WuM-H. WangX-Y. Internal Medicine of Traditional Chinese Medicine.Beijing:China Traditional Chinese Medicine Press.20127:288288
    [Google Scholar]
  10. LiuT. GaoY-G. WuL. HeQ-C. LiangN. ZhangQ-P. An overview of the changes in the etiology and pathogenesis of acute cerebral hemorrhage.Liaoning Journal of Traditional Chinese Medicine.20154261221122210.13192/j.issn.1000‑1719.2015.06.025
    [Google Scholar]
  11. LiuT. GaoY-G. HuangS-W. HeQ. HuangD-Q. ZhangY-K. HeQ-C. Effects of Jianshen Lishui Granules on the expression of caveolin-1 in rats with experimental intracerebral hemorrhag.Shizhen Traditional Chinese Medicine.201526112625262710.3969/j.issn.1008‑0805.2015.11.022
    [Google Scholar]
  12. ChenW. HuangS-W. GaoY-G. HeQ. HeQ-C. HuangD-Q. ZhangY-K. LiuT. Effects of Jianshen Lishui granules on neurological damage and neuronal apoptosis in rats with cerebral hemorrhage.Pharmaceutical Research201534949750010.13506/j.cnki.jpr.2015.09.001
    [Google Scholar]
  13. GaoY-G. HuangD-Q. LiuT. ZhangY-K. HeQ-C. LiuY-H. MoQ-Z. Effect of Jianshen Lishui prescription on C-reactive protein and procalcitonin in patients with acute cerebral hemorrhage.Journal of Hainan Medical College.2021271397898210.13210/j.cnki.jhmu.20210303.004
    [Google Scholar]
  14. HanL-W. ChenS-J. DongR. ZhangY-G. WangX-J. Application progress of network pharmacology in the study of complex mode of action of traditional Chinese medicine.Shandong Science.20213406223110.3976/j.issn.1002‑4026.2021.06.004
    [Google Scholar]
  15. ZhangG-B. LiQ-Y. ChenQ-L. SuS-B. Network pharmacology: a new approach for chinese herbal medicine research.Evid. Based Complement. Alternat. Med.2013201362142310.1155/2013/621423, 23762149
    [Google Scholar]
  16. BaptisteB. KarineA. PierreD. OlivierT. Network-based Approaches in Pharmacology.Mol. Inform.2017361011110.1002/minf.201700048, 28692140
    [Google Scholar]
  17. ZhaoL. ZhangH. LiN. ChenJ-M. XuH. WangY-J. LiangQ-Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.J. Ethnopharmacol.202330911630610.1016/j.jep.2023.116306,36858276
    [Google Scholar]
  18. XiaoY-G. WuH-B. ChenJ-S. LiX. QiuZ-K. Exploring the Potential Antidepressant Mechanisms of Pinellia by Using the Network Pharmacology and Molecular Docking.Metab. Brain Dis.20223741071109410.1007/s11011‑022‑00930‑9,35230627
    [Google Scholar]
  19. HuangM-W. YangH-J. ZhouX-C. GeF-C. J,S-G.; Tu, T-F.; Xie,Y-Y.; C,X-Y. Advances on network pharmacology in ethnomedicine research.Zhongguo Zhongyao Zazhi201944153187319410.19540/j.cnki.cjcmm.20190711.201
    [Google Scholar]
  20. XuX. ZhangC. LiP-D. ZhangF-L. GaoK. ChenJ-X. ShangH-C. Drug-symptom networking:Linking drug-likeness screening to drug discovery.Pharmacol. Res.201610310511310.1016/j.phrs.2015.11.015,26615785
    [Google Scholar]
  21. HuangL. XieD-L. YuY-R. LiuH-L. ShiY. ShiT-L. WenC-P. TCMID 2.0: a comprehensive resource for TCM.Nucleic Acids Res.201846D1D1117D112010.1093/nar/gkx1028, 29106634
    [Google Scholar]
  22. ShiP-Y. XieY-J. XieR-F. LinZ. YaoH. WuS. An Integrated Pharmacokinetic Study of an Acanthopanax senticosus Extract Preparation by Combination of Virtual Screening, Systems Pharmacology,and Multi-Component Pharmacokinetics in Rats.Front. Pharmacol.202011129510.3389/fphar.2020.01295,32922299
    [Google Scholar]
  23. RossanaZ. SandraO. UniProt, C. UniProt Tools: BLAST, Align, Peptide Search, and ID Mapping.Curr. Protoc.202333e69710.1002/cpz1.697,36943033
    [Google Scholar]
  24. GilS. InbarP. DanitO-L. AnnaA. TsviyaO. ShaharZ. MichalT. FridaB SimonF. RonN. YaronG-G. , Davi,d W.; Dvir, D.; Asher, K.; Yaron, M.; Sergey, K.; Tsippi, I-S.; Hagit, NB.; Noa, R.; Marilyn, S.; Doron, L.. VarElect: the phenotype-based variation prioritizer of the GeneCards Suite. BMC Genomics.,201617 Suppl 2Suppl 244410.1186/s12864‑016‑2722‑227357693
    [Google Scholar]
  25. WangX. WangQ. WangK. NiQ-B. Li, H.; Su, Z-Q.; Xu,Y-Z. Is Immune Suppression Involved in the Ischemic Stroke? A Study Based on Computational Biology.Front. Aging Neurosci.20221483049410.3389/fnagi.2022.830494,35250546
    [Google Scholar]
  26. JasmineL-B. VioletK. HaroldL. AdaH. JoannB. Is Bioinformatics for medical students: a 5-year experience using OMIM® in medical student education.Genet. Med.201921249349710.1038/s41436‑018‑0076‑7, 29930391
    [Google Scholar]
  27. CynthiaJ.G. AllanP.D. ThomasC.W. BenjaminL.K. JoleneA.W. DavidM.R. JaneA.H. CarolynJ.M. Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database.Environ. Health Perspect.2016124101592159910.1289/EHP174, 27170236
    [Google Scholar]
  28. K.E R.;, Kavishwar, B.W.; Liu,H-F. Towards pathway curation through literature mining-a case study using PharmGKB.Pac. Symp. Biocomput.201435236324297561
    [Google Scholar]
  29. XuX-Y. LuoH-Y. ChenQ. WangZ-K. ChenX-X. LiX-P. ChenH. WangM. XuY-Y. DaiM. WangJ-W. HuangX-K. WuB. LiY-P. Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking.Front. Pharmacol.202213104706110.3389/fphar.2022.1047061, 36532774
    [Google Scholar]
  30. NadezhdaT.D. JohnH.M. JanG. LarsJ.J. Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data.J. Proteome Res.201918262363210.1021/acs.jproteome.8b00702, 30450911
    [Google Scholar]
  31. LiX. WeiS-Z. NiuS-Q. MaX. LiH-T. JingM-Y. ZhaoYL. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis.Comput. Biol. Med.202214410538910.1016/j.compbiomed.2022.105389, 35303581
    [Google Scholar]
  32. DamianS. AnnikaL.G. DavidL. AlexanderJ. StefanW. JaimeH-C. MilanS. NadezhdaT.D. JohnH.M. PeerB. LarsJ.J. ChristianvM. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.Nucleic Acids Res.201947D1D607D61310.1093/nar/gky1131, 30476243
    [Google Scholar]
  33. HuangL. LiaoL. CathyH.W. Evolutionary analysis and interaction prediction for protein-protein interaction network in geometric space.PLoS One2017129e018349510.1371/journal.pone.0183495, 28886027
    [Google Scholar]
  34. LiZ-G. AndreiA.I. RinaS. ValentinaG-P. QiQ. LiuS-L. PhilipW. ElizabethM. LaurenR. CauP. ChenX-Q. MoX-L. BrianR. ZhouW. AdamM. SaharH. ChenX. MargaretA.J. MichaelA.W. CarlosM. LeeA.D.C. DuY-H. FadloR.K. HaianF. The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategies.Nat. Commun.201781435610.1038/ncomms14356, 28205554
    [Google Scholar]
  35. GuoH. ZhangY-J. HuZ-F. WangL. DuH-Y. Screening and identification of biomarkers associated with the immune infiltration of intracerebral hemorrhage.J. Clin. Lab. Anal.2022365e2436110.1002/jcla.24361, 35318719
    [Google Scholar]
  36. FlorenceC. ValentinL. YvesV. GO Enrichment Analysis for Differential Proteomics Using ProteoRE.Methods Mol. Biol.2021236117919610.1007/978‑1‑0716‑1641‑3_11, 34236662
    [Google Scholar]
  37. DuJ-L. LiM-L. YuanZ-F. GuoM-C. SongJ-Z. XieX-Z. ChenY-L. A decision analysis model for KEGG pathway analysis.BMC Bioinformatics201617140710.1186/s12859‑016‑1285‑1, 27716040
    [Google Scholar]
  38. AndreaB. MarcoF. JonathanS.M. StefanoM. Molecular docking methodologies.Methods Mol. Biol.201392433936010.1007/978‑1‑62703‑017‑5_13, 23034755
    [Google Scholar]
  39. RobbieP.J. TimA.H. ElmarK. MaartenL. HekkelmanR.W.W.H. ReinhardS. ChrisS. GertV. A series of PDB related databases for everyday needs.Nucleic Acids Res.201139Database issueD411D41910.1093/nar/gkq1105,21071423
    [Google Scholar]
  40. WendyW.T. ShirleyW.I.S. PyMOL mControl: Manipulating molecular visualization with mobile devices.Biochem. Mol. Biol. Educ.2017451768310.1002/bmb.20987, 27292587
    [Google Scholar]
  41. LakkyongH. In-YoungC. Sung-EunK. Il-GyuK. Mal-SoonS. Chang-JuK. Sang-HoonK. Jun-JangJ. Jun-YoungC. Jae-WooY. Dexmedetomidine ameliorates intracerebral hemorrhage- induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus.Int. J. Mol. Med.20133151047105610.3892/ijmm.2013.1301, 23503673
    [Google Scholar]
  42. YangL-Q. XuH-B. ChenY. MiaoC-Y. ZhaoY. XingY. ZhangQ. Melatonin: Multi-target mechanism against diminished ovarian reserve based on network pharmacology.Front. Endocrinol.202112663050463052110.3389/fendo.2021.630504, 33959095
    [Google Scholar]
  43. ZhangX-J. LiH-Y. HuS-C. ZhangL-Y. LiuC-Y. ZhuC-H. LiuR-C. LiC-Y. Brain edema after intracerebral hemorrhage in rats: the role of inflammation.Neurol. India200654440240710.4103/0028‑3886.28115,17114852
    [Google Scholar]
  44. WilkinsonD.A. PandeyA.S. ThompsonB.G. KeepR.F. HuaY. XiG-H. Injury mechanisms in acute intracerebral hemorrhage.Neuropharmacology., 2018134Pt B24024810.1016/j.neuropharm.2017.09.03328947377
    [Google Scholar]
  45. BenameurT. SoletiR. PorroC. The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases.Nutrients20211341318132410.1016/j.neuropharm.2017.09.033,28947377
    [Google Scholar]
  46. NitiS. MarioA.T. SeongS.A.A. Phytosterols:Potential Metabolic Modulators in Neurodegenerative Diseases.Int. J. Mol. Sci.20212222122551226010.3390/ijms222212255, 34830148
    [Google Scholar]
  47. LinX-X. PengQ-Z. ZhangJ-J. LiX. HuangJ-R. DuanS. ZhangW-S. Quercetin Prevents Lipopolysaccharide Induced Experimental Preterm Labor in Mice and Increases Offspring Survival Rate.Reprod. Sci.20202741047105710.1007/s43032‑019‑00034‑3, 32157554
    [Google Scholar]
  48. JasonH. TangY. MichaelJ.Z. TsonwinH. AruniB. SanjayS. MatthewS. Atf3 negatively regulates Ptgs2/Cox2 expression during acute inflammation.Prostaglandins Other Lipid Mediat.2015116-117495610.1016/j.prostaglandins.2015.01.001, 25619459
    [Google Scholar]
  49. WangF. BaiJ. LiF. LiuJ. WangY-L. LiN. WangY-Q. XuJ. LiuW-B. XuL. ChenL. Investigation of the mechanism of the anti-cancer effects of Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&P) on melanoma via network pharmacology and experimental verification.Front. Pharmacol.20221389573810.3389/fphar.2022.895738, 36034875
    [Google Scholar]
  50. WararutB. KanokpornS. SupapS. ChatchoteT. Uvaria rufa Blume attenuates benign prostatic hyperplasia via inhibiting 5α-reductase and enhancing antioxidant status.J. Ethnopharmacol.201619448349410.1016/j.jep.2016.10.036, 27732901
    [Google Scholar]
  51. WararutB. KanokpornS. SupapS. ChatchoteT. Dietary intake of plant sterols stably increases plant sterol levels in the murine brain.J. Lipid Res.201253472673510.1016/j.jep.2016.10.036, 27732901
    [Google Scholar]
  52. FengL. LiuT-T. HuoX-K. TianX-G. WangC. LvX. NingJ. ZhaoW-Y. ZhangB-J. SunC-P. MaX-C. Alisma genus: Phytochemical constituents, biosynthesis, and biological activities.Phytother. Res.20213541872188610.1002/ptr.6933, 33184919
    [Google Scholar]
  53. GabrielS.G-P. PaulR.S. MaxF. ChiaraG-P. TheoD. MeaghanS. CyndyD.S. CesarV. B. Mannitol-enhanced delivery of stem cells and their growth factors across the blood-brain barrier.Cell Transplant. 2014234- 553153910.3727/096368914X67833724480552
    [Google Scholar]
  54. ZhouY. WangY-C. WangJ. AnneS.R. YangQ-W. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation.Prog. Neurobiol.2014115254410.1016/j.pneurobio.2013.11.003, 24291544
    [Google Scholar]
  55. OliverD. AliH.B. Signaling pathways in cancer and embryonic stem cells.Stem Cell Rev.20073171710.1007/s12015‑007‑0004‑8,17873377
    [Google Scholar]
  56. LiuB-H. ZhouD. GuoY. ZhangS. GuoY-M. GuoT-T. ChenX-Y. GongY-N. TangH-L. XuZ-F. Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway.Chin. J. Integr. Med.202127429129910.1007/s11655‑021‑3326‑5,33515398
    [Google Scholar]
  57. SongD-P. JiY-B. HuangX-W. MaY-Z. FangC. QiuL-H. TanX-X. ChenY-M. WangS-N. ChangJ-L. GuoF-Y. Lithium attenuates blood-brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β-catenin signaling-dependent mechanism in mice.CNS Neurosci. Ther.202228686287210.1111/cns.13832,35343071
    [Google Scholar]
  58. GuoR-L. WangX. FangY-N. ChenX-J. ChenK. HuangW-T. ChenJ. HuJ. LiangF. DuJ-T. ConfidenceD. TianX-X. LinL. rhFGF20 promotes angiogenesis and vascular repair following traumatic brain injury by regulating Wnt/β-catenin pathway.Biomed. Pharmacother.202114311220010.1016/j.biopha.2021.112200,34649342
    [Google Scholar]
  59. JacquesA.S. SofíaD.M. AlejandraC.V. Retroactive signaling in short signaling pathways.PLoS One201277e4080610.1371/journal.pone.0040806,22848403
    [Google Scholar]
  60. ChenM-H. ChenX-X. HuX-Z. DaiJ-X. SunJ. Androgen receptor contributes to microglial/macrophage activation in rats with intracranial hemorrhage by mediating the JMJD3/Botch/Notch1 axis.Neurosci. Lett.202176513628310.1016/j.neulet.2021.136283,34624395
    [Google Scholar]
  61. ChenB. ChenZ-H. LiuM-J. GaoX-R. ChengY-J. WeiY-X. WuZ-B. CuiD-R. ShangH-B. Inhibition of neuronal ferroptosis in the acute phase of intracerebral hemorrhage shows long-term cerebroprotective effects.Brain Res. Bull.201915312213210.1016/j.brainresbull.2019.08.013,31442590
    [Google Scholar]
  62. JohnP. Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination.Mol. Cell. Endocrinol.200929918910010.1016/j.mce.2008.11.025,19103250
    [Google Scholar]
  63. CristinaC. SimonD.T-R. Brain Edema in Chronic Hepatic Encephalopathy.J. Clin. Exp. Hepatol.20199336238210.1016/j.jceh.2019.02.003,31360029
    [Google Scholar]
  64. FanL-W. KathleenC. AbhayB. PangY. Rapid transport of insulin to the brain following intranasal administration in rats.Neural Regen. Res.20191461046105110.4103/1673‑5374.250624,30762017
    [Google Scholar]
  65. MarjoM. EinariA.N. MinnaU.K. JormaJ.P. Crosstalk between androgen and pro-inflammatory signaling remodels androgen receptor and NF-κB cistrome to reprogram the prostate cancer cell transcriptome.Nucleic Acids Res.201745261963010.1093/nar/gkw855,27672034
    [Google Scholar]
  66. FrederickD.T. MathewS.L. MoZ. HelenC. OdisP. JamesJ.F. JessicaJ.G. AdrienneD.C. KevinM.H. MarkR.P. K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif.Proc. Natl. Acad. Sci. USA2015112377978410.1073/pnas.1412811112,25561545
    [Google Scholar]
  67. GaoS. JeffreyN. ShantelW. EthanA.W. CalebR. AdibA.A. NalinG. JosephT.S. DanielL.C. StevenW.H. TarikT. ChristopherP.H. NerissaK. BrianP.W. CharlesE.M. MichaelT.L. SuH. LudmilaP. HelenK. Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype.J. Neurosurg.2021136114815510.3171/2020.11.JNS202031,34214981
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073256436231031100059
Loading
/content/journals/cchts/10.2174/0113862073256436231031100059
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