Advertisement

Neurotoxicity Research

, Volume 36, Issue 4, pp 756–763 | Cite as

Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro

  • Hongyan LongEmail author
  • Jie Ruan
  • Mengjiao Zhang
  • Chunyan Wang
  • Yaruo Huang
Original Article
  • 68 Downloads

Abstract

Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated.

The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats.

TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-κB pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured.

Data indicated that RH significantly decreased IL-6, IL-1β, and TNF-α in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-κBp65, P-IκBα, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum.

Our results shown that the regulation of BDNF/NF-κB pathway might be involved in the effects of RH on TS model.

Keywords

Rhynchophylline Tourette syndrome BDNF/NF-κB 

Notes

Funding Source

This work was financially supported by the National Natural Science Foundation of China (81774364, 81603661) and supported by the Nanjing Medical Science and technique Development Foundation (QRX17192).

Authors’ Contributions

Long Hongyan and Ruan Jie designed the experiments and wrote articles, Zhang Mengjiao and Wang Chunyan performed the experiments, and Huang Yaruo analyzed and processed data.

Compliance with Ethical Guidelines

All of the experiments were performed in full compliance with the guidelines of the Principles of Laboratory Animal Care and the Guide for the Care and Use of Laboratory Animals approved by the National Institutes of Health (NIH Publication No. 85-23, revised 1996). Animal care and experimental protocols were approved by the Nanjing University of Chinese Medicine Committee.

References

  1. Bellinghausen I, König B, Böttcher I, Knop J, Saloga J (2005) Regulatory activity of human CD4 + CD25 + T cells depends on allergen concentration, type of allergen and atopy status of the donor. Immunology 116:103–111CrossRefGoogle Scholar
  2. Ben-Shlomo Y, Scharf JM, Miller LL, Mathews CA (2016) Parental mood during pregnancy and post-natally is associated with offspring risk of Tourette syndrome or chronic tics: prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Eur Child Adolesc Psychiatry 25:1–9CrossRefGoogle Scholar
  3. Chang JW, Choi JY, Lee BW, Kang UJ, Chung SS (2002) Unilateral globus pallidus internus stimulation improves delayed onset post-traumatic cervical dystonia with an ipsilateral focal basal ganglia lesion. J Neurol Neurosurg Psychiatry 73:588–590CrossRefGoogle Scholar
  4. Fan X, Zhu JY, Sun Y, Luo L, Yan J, Yang X, Yu J, Tang WQ, Ma W, Liang HP (2017) Evodiamine inhibits zymosan-induced inflammation in vitro and in vivo: inactivation of NF-κB by inhibiting IκBα phosphorylation. Inflammation 40:1012–1027CrossRefGoogle Scholar
  5. Fründt O, Woods D, Ganos C (2017) Behavioral therapy for Tourette syndrome and chronic tic disorders. Neurol Clin Pract 7:148–156CrossRefGoogle Scholar
  6. Guo L, Ren L, Zhang C (2018) Relationship between depression and inflammatory factors and brain-derived neurotrophic factorin patients with perimenopause syndrome. Exp Ther Med 15:4436–4440PubMedPubMedCentralGoogle Scholar
  7. Hawksley J, Cavanna AE, Nagai Y (2015) The role of the autonomic nervous system in Tourette syndrome. Front Neurosci 9:117CrossRefGoogle Scholar
  8. Ho YC, Lee SS, Yang ML, Huang-Liu R, Lee CY, Li YC, Kuan YH (2017) Zerumbone reduced the inflammatory response of acute lung injury in endotoxin-treated mice via Akt-NFκB pathway. Chem Biol Interact 27:9–14CrossRefGoogle Scholar
  9. Long H, Chunyan W, Yue’e Y (2017a) LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats. Metab Brain Dis 32:1619–1625CrossRefGoogle Scholar
  10. Long H, Zhenyang S, Chunyan W, Qingqing P (2017b) Lipopolysaccharide aggravated DOI-induced Tourette syndrome: elaboration for recurrence of Tourette syndrome. Metab Brain Dis 32:1929–1934CrossRefGoogle Scholar
  11. Lu Z, Li Y, Wang J, Che Y, Sun S, Huang J, Chen Z, He J (2017) Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/snail pathway. J Exp Clin Cancer Res 36:54CrossRefGoogle Scholar
  12. Ma T, Wang Z, Zhang YM, Luo JG, Kong LY (2017) Bioassay-guided isolation of anti-inflammatory components from the bulbs of Lilium brownii var. viridulum and identifying the underlying mechanism through acting on the NF-κB/MAPKs pathway. Molecules.  https://doi.org/10.3390/molecules22040506 CrossRefGoogle Scholar
  13. Sakakibara I (1994) Discrimination of nine species of Uncaria (Rubiaceae), original plants of Chinese natural medicine, Diao-Teng-gou, based on stem anatomy and HPLC analysis. Journal of Japanese Botany 74:42–52Google Scholar
  14. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV (2016) Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife.  https://doi.org/10.7554/eLife.15092
  15. Tizabi Y, Russell LT, Johnson M, Darmani NA (2001) Nicotine attenuates DOI-induced head-twitch response in mice: implications for tourette syndrome. Prog Neuro-Psychopharmacol Biol Psychiatry 25:1445–1457CrossRefGoogle Scholar
  16. Worbe Y, Marrakchi-Kacem L, Lecomte S, Valabregue R, Poupon F, Guevara P, Tucholka A, Mangin JF, Vidailhet M, Lehericy S, Hartmann A, Poupon C (2015) Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome. Brain 138:472–482CrossRefGoogle Scholar
  17. Xu D, Lian D, Wu J, Liu Y, Zhu M, Sun J, He D, Li L (2017) Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis. Neuroinflammation 14:156CrossRefGoogle Scholar
  18. Zhang W, Wei L, Yu W, Cui X, Liu X, Wang Q, Wang S (2016) Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome. Neuropsychiatr Dis Treat 12:1233–1242CrossRefGoogle Scholar
  19. Zhang F and Sun AS (2010) Effects of isorhynchophylline on angiotensinII-induced proliferation in rat vascular smooth muscle cells. Selected and awarded essays on outstanding academic papers of natural science in Guizhou provinceGoogle Scholar
  20. Zinna S, Kyriakopoulos M (2016) Clinical correlates of comorbid chronic tics and Tourette syndrome in a National Inpatient Children’s Unit. Eur Psychiatry 33:S137–S137CrossRefGoogle Scholar
  21. Zhou JY, Zhou SW (2010) Antihypertensive and neuroprotective activities of rhynchophylline: the role of rhynchophylline in neurotransmission and ion channel activity. J Ethnopharmacol 132:15–27CrossRefGoogle Scholar
  22. Zhou JY, Zhou SW (2012) Isorhynchophylline: a plant alkaloid with therapeutic potential for cardiovascular and central nervous system diseases. Fitoterapia 83:617–626CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hongyan Long
    • 1
    Email author
  • Jie Ruan
    • 1
  • Mengjiao Zhang
    • 2
  • Chunyan Wang
    • 2
  • Yaruo Huang
    • 2
  1. 1.Central Laboratory, Nanjing Hospital of Chinese MedicineThe Third Affiliated Hospital of Nanjing University of Chinese MedicineNanjingChina
  2. 2.Nanjing University of Chinese MedicineNanjingChina

Personalised recommendations