UPLC-Q-TOF-MS/MS Combined with Network Pharmacology, Molecular Docking, and Animal Verification Reveals the Mechanism of Insomnia Treatment by Shen Qi Wu Wei Zi Capsules


Cite item

Full Text

Abstract

Background:Shen Qi Wu Wei Zi capsules (SQWWZ) are often used to treat insomnia; however, the potential therapeutic mechanism is still unclear.

Objective:This study aimed to investigate the mechanism underlying the therapeutic effects of the Shen Qi Wu Wei Zi capsules on insomnia.

Methods:The components of SQWWZ were identified using the UPLC-Q-TOF-MS/MS technique in conjunction with relevant literature. Insomnia-related targets were searched in the GeneCards and DisGeNET databases, and the intersection targets were obtained using a Venn diagram. A component-target-insomnia network diagram was constructed using Cytoscape 3.7.2 software. Core targets underwent GO and KEGG enrichment analyses. Molecular docking techniques were employed to verify the key proteins involved in the pathway and their corresponding compounds. Insomnia was induced in SD rats through the intraperitoneal injection of pchlorophenylalanine (DL-4-chlorophenylalanine, PCPA). The rats were treated orally with SQWWZ, and the serum levels of 5-HT and GABA in each group were determined using ELISA. Histological analysis of hippocampal tissue sections from the rats was performed using HE staining.

Results:Using UPLC-Q-TOF-MS/MS and reviewing relevant literature, we identified 49 components of SQWWZ. Additionally, we obtained 1,043 drug targets and 367 insomnia-related targets. Among these, 82 targets were found to be common to both drug and insomnia targets. Following drug administration, rats in the treatment group exhibited a significant increase in the serum levels of 5-HT and GABA. Moreover, histological analysis using HE staining revealed neatly arranged hippocampal neuronal cells in the treated rats.

Conclusion:The active components of SQWWZ had good inhibition of insomnia. This study provides a reference and guidance for the in-depth study of SQWWZ for the treatment of insomnia.

About the authors

Fengyun Bai

, Shaanxi Dongtai Pharmaceutical Company

Email: info@benthamscience.net

Jie Wang

Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Ning Xia

Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine,

Email: info@benthamscience.net

Ying Sun

, Shaanxi Dongtai Pharmaceutical Company

Email: info@benthamscience.net

Yundong Xie

Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Chongbo Zhao

Key Laboratory of Basic and New Drug Research of Traditional Chinese MedicineChinese Medicine,Xianyang, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Jing Sun

Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Xiaofei Zhang

Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

References

  1. Bastien, C.H. Insomnia: Neurophysiological and neuropsychologicalApproaches. Neuropsychol. Rev., 2011, 21(1), 22-40. doi: 10.1007/s11065-011-9160-3 PMID: 21249453
  2. Morin, C.; Leblanc, M.; Daley, M.; Gregoire, J.; Mérette, C. Epidemiology of insomnia: Prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med., 2006, 7(2), 123-130. doi: 10.1016/j.sleep.2005.08.008 PMID: 16459140
  3. Moul, D.E.; Nofzinger, E.A.; Pilkonis, P.A.; Houck, P.R.; Miewald, J.M.; Buysse, D.J. Symptom reports in severe chronic insomnia. Sleep, 2002, 25(5), 548-558. doi: 10.1093/sleep/25.5.548 PMID: 12150322
  4. Chen, J.; Jakshanbai, S. Advances in the treatment of insomnia. Xinjiang Chinese Medicine, 2023, 41(01), 96-99.
  5. Hui, C.; Jisheng, C.; Jianchun, M. Sebuah studi tentang mekanisme kerja senyawa obat herbal Cina untuk insomnia berdasarkan penggalian data dan farmakologi jaringan. Farmasi Hari Ini, 2022, 32(01), 30-34.
  6. Zammit, G.K. Subjective ratings of the characteristics and sequelae of good and poor sleep in normals. J. Clin. Psychol., 1988, 44(2), 123-130. doi: 10.1002/1097-4679(198803)44:23.0.CO;2-D PMID: 3360924
  7. Fortier-Brochu, É.; Beaulieu-Bonneau, S.; Ivers, H.; Morin, C.M. Insomnia and daytime cognitive performance: A meta-analysis. Sleep Med. Rev., 2012, 16(1), 83-94. doi: 10.1016/j.smrv.2011.03.008 PMID: 21636297
  8. Morin, C.M.; Jarrin, D.C. Epidemiology of insomnia. Sleep Med. Clin., 2022, 17(2), 173-191. doi: 10.1016/j.jsmc.2022.03.003 PMID: 35659072
  9. Anna Karin, H.; Hössjer, O.; Bellocco, R.; Ye, W.; Trolle, L.Y.; Åkerstedt, T. Insomnia in the context of short sleep increases suicide risk. Sleep, 2021, 44(4), zsaa245. doi: 10.1093/sleep/zsaa245 PMID: 33216134
  10. Wilson, S.J.; Nutt, D.J.; Alford, C.; Argyropoulos, S.V.; Baldwin, D.S.; Bateson, A.N.; Britton, T.C.; Crowe, C.; Dijk, D-J.; Espie, C.A.; Gringras, P.; Hajak, G.; Idzikowski, C.; Krystal, A.D.; Nash, J.R.; Selsick, H.; Sharpley, A.L.; Wade, A.G. British association for psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J. Psychopharmacol., 2010, 24(11), 1577-1601. doi: 10.1177/0269881110379307 PMID: 20813762
  11. Wilson, S.; Anderson, K.; Baldwin, D.; Dijk, D.J.; Espie, A.; Espie, C.; Gringras, P.; Krystal, A.; Nutt, D.; Selsick, H.; Sharpley, A. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: An update. J. Psychopharmacol., 2019, 33(8), 923-947. doi: 10.1177/0269881119855343 PMID: 31271339
  12. Otmani, S.; Metzger, D.; Guichard, N.; Danjou, P.; Nir, T.; Zisapel, N.; Katz, A. Effects of prolonged‐release melatonin and zolpidem on postural stability in older adults. Hum. Psychopharmacol., 2012, 27(3), 270-276. doi: 10.1002/hup.2219 PMID: 22350925
  13. Wang, W.; Wang, Y.; Guo, Q.; Li, H.; Wang, Z.; Li, J.; Li, T.; Tang, T.; Wang, Y.; Jia, Y.; Wang, Y.; Zou, J.; Shi, Y.; Guo, D.; Yang, M.; Zhang, X.; Sun, J. Valerian essential oil for treating insomnia via the serotonergic synapse pathway. Front. Nutr., 2022, 9, 927434. doi: 10.3389/fnut.2022.927434 PMID: 35990355
  14. Singh, A.; Zhao, K. Treatment of insomnia with traditional chinese herbal medicine. Int. Rev. Neurobiol., 2017, 135, 97-115. doi: 10.1016/bs.irn.2017.02.006 PMID: 28807167
  15. Bian, Z.; Zhang, W.; Tang, J.; Fei, Q.; Hu, M.; Chen, X.; Su, L.; Fei, C.; Ji, D.; Mao, C.; Tong, H.; Yuan, X.; Lu, T. Mechanisms underlying the action of Ziziphi Spinosae semen in the treatment of insomnia: A study involving network pharmacology and experimental validation. Front. Pharmacol., 2021, 12, 752211. doi: 10.3389/fphar.2021.752211 PMID: 35002696
  16. Hu, J.; Teng, J.; Wang, W.; Yang, N.; Tian, H.; Zhang, W.; Peng, X.; Zhang, J. Clinical efficacy and safety of traditional Chinese medicine Xiao Yao San in insomnia combined with anxiety. Medicine, 2021, 100(43), e27608. doi: 10.1097/MD.0000000000027608 PMID: 34713840
  17. Liu, H. Drug metabolism and pharmacokinetics of the main active ingredients of Schisandra chinensis; Fujian Medical University, 2019.
  18. Li, L. Progress of research on the chemical composition and pharmacological effects of Radix Codonopsis pilosulae. J. Chin. Med., 2023, 51(03), 112-115.
  19. Zhen, W.; Cao, L.; Du, X. Progress in the study of the common pair-combining mechanism of Astragalus. J. Liaoning Univ. Chin. Med., 2023, 29(1), 89-95.
  20. Huang, N. Radix et Rhizoma Ginseng HPLC fingerprinting was combined with several chemical pattern recognition studies. Farmasi Terapan Modern di Tiongkok, 2022, 39(16), 2103-2111.
  21. Wag, Z. Research progress on the pharmacological effects and quality control of the active ingredient Astragalus membranaceus. Drug Eval. Stud., 2023, 46(04), 917-924.
  22. Wang, C. Integrating metabolomics and intestinal flora to explore the characteristics of the mechanism of action of raw and fried tamarind dates in improving sleep quality. J. Pharm. Sci., 2023, 13, 1184786.
  23. Yang, C. A study on the spectrum effect relationship between the sedative and hypnotic effects of fried jujube seeds based on grayscale correlation analysis. Chin. Herb. Med., 2021, 52(17), 5267-5274.
  24. Li, X. Progress of research on sedative and hypnotic active ingredients as well as the pharmacological effects of tamarind dates. Chin. J. Trad. Chin. Med., 2022, 40(02), 23-31.
  25. Xie, C.; Gu, Y.; Wang, W.W.; Lu, L.; Fu, D.; Liu, A.; Li, H.; Li, J.; Lin, Y.; Tang, W.; Zheng, G. Efficacy and safety of Suanzaoren decoction for primary insomnia: A systematic review of randomized controlled trials. BMC Complement. Altern. Med., 2013, 13(1), 18. doi: 10.1186/1472-6882-13-18 PMID: 23336848
  26. Liu, q. she N seven W U seat capsule int and treatment of insomnia 30 cases Z and ginger. J. Tradit. Chin. Med., 2009, 44(03), 201.
  27. Fan, Y.; Sun, X. Clinical efficacy observation on the treatment of insomnia with medicinal tea combined with shenqi wuweizi capsule Chinese community physicians, 2017, 33(15), 88-90.
  28. Yan, Q. The efficacy of Ginseng and Astragalus Wu Wei Zi tablets in treating 46 cases of insomnia. Hainan Medicine, 2012, 23(11), 43-44.
  29. Zhao, L.; Zhang, H.; Li, N.; Chen, J.; Xu, H.; Wang, Y.; Liang, Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J. Ethnopharmacol., 2023, 309, 116306. doi: 10.1016/j.jep.2023.116306 PMID: 36858276
  30. Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional Chinese Medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123. doi: 10.3389/fphar.2019.00123 PMID: 30846939
  31. Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690. doi: 10.1038/nchembio.118 PMID: 18936753
  32. Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
  33. Wang, Y.; He, S.; Cheng, X.; Lu, Y.; Zou, Y.; Zhang, Q. UPLC–Q-TOF-MS/MS fingerprinting of Traditional Chinese formula SiJunZiTang. J. Pharm. Biomed. Anal., 2013, 80, 24-33. doi: 10.1016/j.jpba.2013.02.021 PMID: 23511229
  34. Zhang, J.; Jin, Y.; Dong, J.; Xiao, Y.; Feng, J.; Xue, X.; Zhang, X.; Liang, X. Systematic screening and characterization of tertiary and quaternary alkaloids from corydalis yanhusuo W.T. Wang using ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry. Talanta, 2009, 78(2), 513-522. doi: 10.1016/j.talanta.2008.12.002 PMID: 19203617
  35. Zeng, X. Effect of Song Yu’s Calm Formula on the sleep phase of PCPA-induced insomnia rats. Jurnal Kedokteran Tidur Dunia, 2021, 8(01), 7-10.
  36. Guo, H. Changes in activity of cortical NG2 cells caused by PCPA and coexistence of NG2 with sleep-wake related neurons and the intervention effect of sour date soup. World J. Sleep Med., 2022, 8(01), 7-10.
  37. Wu, J. Changes in cortical prefrontal ATP levels at different times in PCPA insomnia rats and the intervention effect of sour date palm soup. Chongqing Medicine, 2017, 46(04), 439-441.
  38. Liu, J. Serum metabolomic study on PCPA-induced insomnia in rats with the classical formula sour date palm soup. Chin. J. Trad. Chin. Med., 2022, 47(06), 1632-1641.
  39. Liu, H. Study on the therapeutic mechanism of sour date palm soup on chlorophenylalanine-induced insomnia rat model. Shandong Science, 2021, 34(06), 32-40.
  40. Nenadic Sviglin, K.; Nedic, G.; Nikolac, M.; Mustapic, M.; Muck-Seler, D.; Borovecki, F.; Pivac, N. Insomnia, platelet serotonin and platelet monoamine oxidase in chronic alcoholism. Neurosci. Lett., 2011, 500(3), 172-176. doi: 10.1016/j.neulet.2011.06.026 PMID: 21722708
  41. Lu, Y. Sleep intervention study of γ-aminobutyric acid in mice with circadian rhythm disorders. J. Nutr., , 1-9.
  42. Wu, D. Effects of Ginseng and Wu Wei Zi tablets on brainstem 5-hydroxytryptamine in insomniac rats. J. Chin. Med., 2010, 51(05), 411.
  43. He, Y. To explore the mechanism of Shenqi Wuweizi tablets in the treatment of insomnia based on network pharmacology. World Trad. Chin. Medi., 2022, 17(18), 2541-2547+2555.
  44. Vgontzas, A.N.; Bixler, E.O.; Lin, H.M.; Prolo, P.; Trakada, G.; Chrousos, G.P. IL-6 and its circadian secretion in humans. Neuroimmunomodulation, 2005, 12(3), 131-140. doi: 10.1159/000084844 PMID: 15905620
  45. Vgontzas, A.N.; Zoumakis, M.; Bixler, E.O.; Lin, H.M.; Prolo, P.; Vela-Bueno, A.; Kales, A.; Chrousos, G.P. Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: Physiologic and therapeutic implications. J. Clin. Endocrinol. Metab., 2003, 88(5), 2087-2095. doi: 10.1210/jc.2002-021176 PMID: 12727959
  46. Lyytinen, J.; Kaakkola, S.; Gordin, A.; Kultalahti, E.R.; Teräväinen, H. Entacapone and selegiline with l-dopa in patients with Parkinson’s disease: An interaction study. Parkinsonism Relat. Disord., 2000, 6(4), 215-222. doi: 10.1016/S1353-8020(00)00012-2 PMID: 10900396
  47. Gay, C.L.; Zak, R.S.; Lerdal, A.; Pullinger, C.R.; Aouizerat, B.E.; Lee, K.A. Cytokine polymorphisms and plasma levels are associated with sleep onset insomnia in adults living with HIV/AIDS. Brain Behav. Immun., 2015, 47, 58-65. doi: 10.1016/j.bbi.2014.11.018 PMID: 25535857
  48. de la Roza, C.; Reinoso-suárez, F. Ultrastructural characterization of relationship between serotonergic and GABAergic structures in the ventral part of the oral pontine reticular nucleus. Neuroscience, 2009, 164(3), 1180-1190. doi: 10.1016/j.neuroscience.2009.08.050 PMID: 19723566
  49. Singh, D.; Singh, P.; Srivastava, P.; Kakkar, D.; Pathak, M.; Tiwari, A.K. Development and challenges in the discovery of 5-HT1A and 5-HT7 receptor ligands. Bioorg. Chem., 2023, 131, 106254. doi: 10.1016/j.bioorg.2022.106254 PMID: 36528920
  50. Oh, D.R.; Kim, Y.; Jo, A.; Choi, E.J.; Oh, K.N.; Kim, J.; Kang, H.; Kim, Y.R.; Choi, C. Sedative and hypnotic effects of Vaccinium bracteatum Thunb. through the regulation of serotonegic and GABAA-ergic systems: Involvement of 5-HT1A receptor agonistic activity. Biomed. Pharmacother., 2019, 109, 2218-2227. doi: 10.1016/j.biopha.2018.10.003 PMID: 30551479
  51. Zhang, H.; Kong, Q.; Wang, J.; Jiang, Y.; Hua, H. Complex roles of cAMP–PKA–CREB signaling in cancer. Exp. Hematol. Oncol., 2020, 9(1), 32. doi: 10.1186/s40164-020-00191-1 PMID: 33292604
  52. Wang, J. Progress on the pharmacological effects of lignocaine. Life Sci., 2013, 25(06), 560-565.
  53. Liu, J.; Zhai, W.M.; Yang, Y.X.; Shi, J.L.; Liu, Q.T.; Liu, G.L.; Fang, N.; Li, J.; Guo, J.Y. GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol. Biochem. Behav., 2015, 128, 41-49. doi: 10.1016/j.pbb.2014.11.003 PMID: 25449359
  54. Wang, L.E.; Bai, Y.J.; Shi, X.R.; Cui, X.Y.; Cui, S.Y.; Zhang, F.; Zhang, Q.Y.; Zhao, Y.Y.; Zhang, Y.H. Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system. Pharmacol. Biochem. Behav., 2008, 90(3), 399-403. doi: 10.1016/j.pbb.2008.03.022 PMID: 18466960
  55. Tabassum, S.; Misrani, A.; Tang, B.; Chen, J.; Yang, L.; Long, C. Jujuboside A prevents sleep loss-induced disturbance of hippocampal neuronal excitability and memory impairment in young APP/PS1 mice. Sci. Rep., 2019, 9(1), 4512. doi: 10.1038/s41598-019-41114-3 PMID: 30872728
  56. You, Z.; Xia, Q.; Liang, F.; Tang, Y.; Xu, C.; Huang, J.; Zhao, L.; Zhang, W.; He, J. Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons. J. Ethnopharmacol., 2010, 128(2), 419-423. doi: 10.1016/j.jep.2010.01.034 PMID: 20083184
  57. Li, L.; Huang, J. Advances in the pharmacological effects of mullein isoflavone glucoside. Journal of Hainan Medical College, 2020, 26(02), 156-160.
  58. Yan, X. Trichothecene isoflavone glycosides modulate SIRT1 signaling pathway to alleviate hippocampal neuronal cell injury. New Chin. Med. Clin. Pharmacol., 2021, 32(06), 758-764.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers