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Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system

  • Yujie Sun
  • Na Zhang
  • Yuxia Qu
  • Yijia Cao
  • Jianhao Li
  • Yuwei Yang
  • Tiange Yang
  • Yikun SunEmail author
Original Article
  • 38 Downloads

Abstract

As a Traditional Chinese Medicine (TCM), Shuangxia Decoction (SXD) has been used to treat insomnia in oriental countries for more than thousands of years and it presents remarkable clinical effects. However, its active pharmacological fraction and the mechanism of sedative-hypnotic effects have not been explored. In this paper, we investigated active pharmacological fraction and revealed the detailed mechanisms underlying the sedative-hypnotic effects of SXD. It showed that SXD water extract compared to ethanol extract possessed better sedative effects on locomotion activity in normal mice and increased sleep duration in subhypnotic dose of sodium pentobarbital-treated mice. SXD alleviated p-chlorophenylalanine (PCPA) -induced insomnia by increasing the content of 5-HT in cortex [F (4, 55) = 12.67], decreasing the content of dopamine (DA) and norepinephrine (NE). Furthermore, SXD enhanced the expression of 5-HT1A and 5-HT2A receptors in hypothalamic and reduced serum levels of IL-1,TNF-α [F (5, 36) = 15.58]. In conclusion, these results indicated that SXD produced beneficial sedative and hypnotic bioactivities mediated by regulating the serotonergic and immune system.

Keywords

Shuangxia decoction PCPA Insomnia Sedative-hypnotic effects Serotonergic system 

Notes

Acknowledgments

We acknowledge financial supports from the National Natural Science Foundation of China (81173521).

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

References

  1. Assefa SZ, Diaz-Abad M, Wickwire EM, Scharf SM (2015) The functions of sleep. Neuroscience 2(3):155–171.  https://doi.org/10.3934/Neuroscience.2015.3.155 CrossRefGoogle Scholar
  2. Atkin T, Comai S, Gobbi G (2018) Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharma Rev 70(2):197.  https://doi.org/10.1124/pr.117.014381 CrossRefGoogle Scholar
  3. Barros HM, Tannhauser MA, Tannhauser SL, Tannhauser M (1991) Enhanced detection of hyperactivity after drug withdrawal with a simple modification of the open-field apparatus. J Pharmacol Methods 26(4):269–275.  https://doi.org/10.1016/0160-5402(91)90037-6 CrossRefPubMedGoogle Scholar
  4. Cespuglio R (2018) Serotonin: its place today in sleep preparation, triggering or maintenance. Sleep Med 41:31–39.  https://doi.org/10.1016/j.sleep.2018.05.034 CrossRefGoogle Scholar
  5. Chen YH, Liu L, Guo QS, Zhu ZB, Zhang LX (2016) Effects of different water management options and fertilizer supply on photosynthesis, fluorescence parameters and water use efficiency of Prunella vulgaris seedlings. Biol Res 49:12.  https://doi.org/10.1186/s40659-016-0069-4 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Hu Y, Wang YN, Zhang GQ, Dong XZ, Liu WW, Liu P (2016) Gan-Dan-Liang-Yi-Tang alleviates p-chlorophenylalanine-induced insomnia through modification of the serotonergic and immune system. Exp Therap Med 12(5):3087.  https://doi.org/10.3892/etm.2016.3737 CrossRefGoogle Scholar
  7. Jeon SJ, Park HJ, Gao Q, Pena IJ, Park SJ, Lee HE, Woo H, Kim HJ, Cheong JH, Hong E, Ryu JH (2015) Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice. Eur J Pharma 762:443–448.  https://doi.org/10.1016/j.ejphar.2015.06.037 CrossRefGoogle Scholar
  8. Jouvet M (1999) Sleep and serotonin: an unfinished story. Neuropsychopharmacology 21:24S–27S.  https://doi.org/10.1016/S0893-133X(99)00009-3 CrossRefPubMedGoogle Scholar
  9. Kim J-W, Han J-Y, Hong JT, Li R, Eun JS, Oh K-W (2011) Ethanol Extract of the Flower Augments Pentobarbital-Induced Sleep Behaviors: Involvement of Cl Channel Activation. Evidence-Based Complementary and Alternative Medicine :1–7.  https://doi.org/10.1155/2011/109164 Google Scholar
  10. Krueger JM (2008) The role of cytokines in sleep regulation. Curr Pharm Design 14(32):3408–3416.  https://doi.org/10.2174/138161208786549281 CrossRefGoogle Scholar
  11. Kuo TH, Pike DH, Beizaeipour Z, Williams JA (2010) Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFκB relish. BMC Neurosci 11(1):17.  https://doi.org/10.1186/1471-2202-11-17 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Liu L, Liu C, Wang Y, Wang P, Li Y, Li B (2015) Herbal medicine for anxiety, depression and insomnia. Curr Neuropharmacol 13(4):481.  https://doi.org/10.2174/1570159X1304150831122734 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Meng F (2003) Self-made Shuangxia decoction for treatment of 56 cases on insomnia. Clin J Tradit Chin Med Anhui 15(5):397 (In Chinese)Google Scholar
  14. Morin CM, Leblanc M, Daley M et al (2006) Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med 7(2):123–130.  https://doi.org/10.1016/j.sleep.2005.08.008 CrossRefPubMedGoogle Scholar
  15. Mouret J, Bobillier P, Jouvet M (1968) Insomnia following parachlorophenylalanin in the rat. Eur J Pharma 5(1):17.  https://doi.org/10.1016/0014-2999(68)90151-9 CrossRefGoogle Scholar
  16. Nishino S (2013) Neurotransmitters and Neuropharmacology of Sleep/Wake Regulations. Encyclop Sleep 395–406.  https://doi.org/10.1016/B978-0-12-378610-4.00087-5 CrossRefGoogle Scholar
  17. Pakalnis A, Splaingard M, Splaingard D, Kring D, Colvin A (2009) Serotonin effects on sleep and emotional disorders in adolescent migraine. Headache 49(10):1486–1492.  https://doi.org/10.1111/j.1526-4610.2009.01392.x CrossRefPubMedPubMedCentralGoogle Scholar
  18. Park SJ, Kim DH, Lee IK, Jung WY, Park DH, Kim JM, Lee KR, Lee KT, Shin CY, Cheong JH, Ko KH, Ryu JH (2010) The ameliorating effect of the extract of the flower of lilacina on drug-induced memory impairments in mice. Food Chem Toxicol 48(6):1671–1676.  https://doi.org/10.1016/j.fct.2010.03.042 CrossRefPubMedGoogle Scholar
  19. Perveen T, Haider S, Zuberi NA, Saleem S, Sadaf S, Batool Z (2014) Increased 5-HT levels following repeated administration of Nigella sativa L. (black seed) oil produce antidepressant effects in rats. Scientia Pharmaceutica 82(1):161–170.  https://doi.org/10.3797/scipharm.1304-19 CrossRefGoogle Scholar
  20. Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep–wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60(1):13–35.  https://doi.org/10.1016/S0301-0082(98)00097-5 CrossRefPubMedGoogle Scholar
  21. Putnins SI, Griffin ML, Fitzmaurice GM, Dodd DR, Weiss RD (2012) Poor sleep at baseline predicts worse mood outcomes in patients with co-occurring bipolar disorder and substance dependence. J Clin Psychiatry 73:703–708.  https://doi.org/10.4088/JCP.11m07007 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H, Gao W (2016) Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat. Physiol Behav 154:114–125.  https://doi.org/10.1016/j.physbeh.2015.11.016 CrossRefPubMedGoogle Scholar
  23. Ryu SY, Oak MH, Yoon SK, Cho DI, Yoo GS, Kim TS, Kim KM (2000) Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris. Planta Med 66:358–360.  https://doi.org/10.1093/carcin/bgr030 CrossRefPubMedGoogle Scholar
  24. Shi Y, Dong JW, Zhao JH, Tang LN, Zhang JJ (2014) Herbal insomnia medications that target GABAergic systems: a review of the psychopharmacological evidence. Curr Neuropharmacol 12:289–302.  https://doi.org/10.2174/1570159X11666131227001243 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Speed T.J., Finan P.H. (2016) Depression, Sleep Disorders, and DA. In: Monti J., Pandi-Perumal S., Chokroverty S. (eds) Dopamine Sleep 191–211.  https://doi.org/10.1007/978-3-319-46437-4_9 CrossRefGoogle Scholar
  26. Uzun S, Kozumplik O, Jakovljević M, Sedić B (2010) Side effects of treatment with benzodiazepines. Psychiatr Danub 22:90–93 https://www.researchgate.net/publication/42372554 PubMedGoogle Scholar
  27. Wu XY, Yang LQ, Li YJ, Wang WW, Zou YM (2009) Study on the sedative and hypnotic effects of Spica prunellae. Lishizhen Med Mate Med Res 20(02):443–444 (In Chinese)Google Scholar
  28. Wu XY, Zhao JL, Zhang M, Li F, Zhao T, Yang LQ (2011) Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum. J Ethnopharmacol 135(2):325–329.  https://doi.org/10.1016/j.jep.2011.03.016 CrossRefPubMedGoogle Scholar
  29. Zeng X, Huang J, Zhou C, Wang X, Zhang Y, Zhang YF (2018) Effect of Songyu Anshen fang on expression of hypothalamic GABA and GABA(B) receptor proteins in insomniac rats induced by Para-chlorophenylalanine. Trop J Pharma Res 17(1):17–22.  https://doi.org/10.4314/tjpr.v17i1.3 CrossRefGoogle Scholar
  30. Zhang C, Mao X, Zhao X, Liu Z, Liu B, Li H, Bi KS, Jia Y (2014) Gomisin N isolated from Schisandra chinensis, augments pentobarbital-induced sleep behaviors through the modification of the serotonergic and GABAergic system. Fitoterapia 96:123–130.  https://doi.org/10.1016/j.fitote.2014.04.017 CrossRefPubMedGoogle Scholar
  31. Zhang ZQ, De G, Geng D, Zhang Q, Tian Y, Xi Y, Wang WQ, Tang HQ, Xu B, Lin HY, Sun YK (2016) Pharmacodynamic study on insomnia-curing effects of Shuangxia decoction in Drosophila melanogaster. Chin J Nat Med 14(9):653–660.  https://doi.org/10.1016/S1875-5364(16)30077-2 CrossRefPubMedGoogle Scholar
  32. Zhang XT, Li L, Chen T, Sun ZY , Tang WW, Wang S, Wang TQ, Wang Y, Zhang H (2018) Research progress in the effect of traditional chinese medicine for invigoration on neurotransmitter related diseases. Evid-Based Compl Alt Med 1–14.  https://doi.org/10.1155/2018/4642018 Google Scholar
  33. Zhao JL (2011) Study on Sedative and Hypnotic Activity of Different Extracts of Pinellia. J Anhui Agric Sci. (In Chinese)Google Scholar
  34. Zhao X, Cui XY, Chen BQ, Chu QP, Yao HY, Ku BS, Zhang YH (2004) Tetrandrine, a bisbenzylisoquinoline alkaloid from Chinese herb Radix, augmented the hypnotic effect of pentobarbital through serotonergic system. Eur J Pharma 506(2):101–105.  https://doi.org/10.1016/j.ejphar.2004.10.046 CrossRefGoogle Scholar
  35. Zhao JL, Wu X, Yang L, Li Y, Wang W, Zou Y (2009) Study on the Sedative and Hypnotic Effects of Spica prunellae. Lishizhen Med Mater Med Res. (In Chinese)Google Scholar
  36. Zhu M, Bowery NG, Greengrass PM, Phillipson JD (1996) Application of radioligand receptor binding assays in the search for CNS active principles from Chinese medicinal plants. J Ethnopharmacol 54(2–3):153–164.  https://doi.org/10.1016/S0378-8741(96)01454-7 CrossRefPubMedGoogle Scholar

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

Authors and Affiliations

  1. 1.School of Chinese Material MedicaBeijing University of Chinese MedicineBeijingChina

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