Gan‑Dan‑Liang‑Yi‑Tang alleviates p‑chlorophenylalanine‑induced insomnia through modification of the serotonergic and immune system

Hu,Yuan; Wang,Yu‑Nin; Zhang,Gang‑Qiang; Dong,Xian‑Zhe; Liu,Wan‑Wan; Liu,Ping

doi:10.3892/etm.2016.3737

Gan‑Dan‑Liang‑Yi‑Tang alleviates p‑chlorophenylalanine‑induced insomnia through modification of the serotonergic and immune system

Authors:
- Yuan Hu
- Yu‑Nin Wang
- Gang‑Qiang Zhang
- Xian‑Zhe Dong
- Wan‑Wan Liu
- Ping Liu
View Affiliations

Affiliations: Department of Clinical Pharmacology and Pharmacy, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, P.R. China
Published online on: September 21, 2016 https://doi.org/10.3892/etm.2016.3737
Pages: 3087-3092

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gan‑Dan‑Liang‑Yi‑Tang (GDLYT) is a Traditional Chinese Medicine that has been historically used for the treatment of insomnia. However, investigations into its pharmacological ingredients and the mechanism underlying its sedative and hypnotic effects remain limited. The present study reported the detailed mechanisms underlying the sedative and hypnotic effects of GDLYT. Kunming mice were administered GDLYT at various sub-hypnotic doses, which underwent sodium pentobarbital treatment test, pentetrazole induced convulsant studies and p-chlorophenylalanine (PCPA) induced insomnia model. Potentiated hypnotic and sedative effects in mice was studied, and also the changes in related neurotransmitter and immune factors were evaluated. The results suggested that GDLYT possessed weak sedative effects on pentetrazole‑induced convulsive activity in normal mice at a dose of 1.3 mg/kg, with an increase in sleep onset in subhypnotic dose of sodium pentobarbital‑treated mice. GDLYT was also able to alleviate insomnia induced by PCPA in the rodent models, and increased 5‑hydroxytryptamine levels in the prefrontal cortex, hippocampus, hypothalamus and corpus striatum of PCPA‑treated rats. Furthermore, the hypnotic effects of GDLYT were modified, which allowed for PCPA‑induced immune system changes, including increased interleukin (IL)‑1β, tumor necrosis factor‑α and IL‑2 expression levels. The results of the present study indicated that GDLYT induced sedative and hypnotic bioactivity by regulating serotonergic activity in the central nervous system and immune system.

View Figures

View References

1	Gang-qiang HX Zhang, Dong Xian-Zhe and Liu Ping: Sedative and Hypnotic Activities of Gandan Liangyi Tang via the Elevation Effects on Amino Acids Neurotranmitters in Mice. Zhong Guo Shi Yan Fang Ji Xue Za Zhi. 19:226–229. 2013.(In Chinese).
2	Yao Y, Jia M, Wu JG, Zhang H, Sun LN, Chen WS and Rahman K: Anxiolytic and sedative-hypnotic activities of polygalasaponins from Polygala tenuifolia in mice. Pharm Biol. 48:801–807. 2010. View Article : Google Scholar : PubMed/NCBI
3	Lee CI, Lee MK and Oh KW: Ethanol extract of Polygalae radix augments pentobarbital-induced sleeping behaviors through GABA(A)ergic systems. Natural Product Sciences. 19:179–185. 2013.
4	Lee SM, Yoon MY and Park HR: Protective effects of Paeonia lactiflora pall on hydrogen peroxide-induced apoptosis in PC12 cells. Biosci Biotechnol Biochem. 72:1272–1277. 2008. View Article : Google Scholar : PubMed/NCBI
5	Mao QQ, Ip SP, Tsai SH and Che CT: Antidepressant-like effect of peony glycosides in mice. J Ethnopharmacol. 119:272–275. 2008. View Article : Google Scholar : PubMed/NCBI
6	Zhang MZ, Zhang QY and Cui GB: Clinical study of XiaoYao-San in the treatment of depressive neurosis. Shan Dong Zhong Yi Yao Da Xue Xue Bao. 22:34–37. 1998.(In Chinese).
7	Shen HX, Jiang ZL, Dong GS, Yang HQ, Jiang R, Li X, Yin P and Chen MM: Anti-motion sickness efficacy of the extracted mixture of Chinese medical herbs and its influence on the blood level of hormones. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 28:398–403. 2012.(In Chinese). PubMed/NCBI
8	TingLi WWSWL: The antidepression effect of ChaoZaiRen. Zhong Yi Yao Xue Bao. 42:13–15. 2014.(In Chinese).
9	Xing-li H: Peng's gouqizaoren decoction intractable insomnia treatment. Shi Yong Zhong Yi Nei Ke Za Zhi. 6:58–59. 2010.(In Chinese).
10	Shi Y, Dong JW, Zhao JH, Tang LN and Zhang JJ: Herbal insomnia medications that target GABAergic systems: A review of the psychopharmacological evidence. Curr Neuropharmacol. 12:289–302. 2014. View Article : Google Scholar : PubMed/NCBI
11	Cao JX, Zhang QY, Cui SY, Cui XY, Zhang J, Zhang YH, Bai YJ and Zhao YY: Hypnotic effect of jujubosides from Semen Ziziphi Spinosae. J Ethnopharmacol. 130:163–166. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhao X, Cui XY, Chen BQ, Chu QP, Yao HY, Ku BS and Zhang YH: Tetrandrine, a bisbenzylisoquinoline alkaloid from Chinese herb radix, augmented the hypnotic effect of pentobarbital through serotonergic system. Eur J Pharmacol. 506:101–105. 2004. View Article : Google Scholar : PubMed/NCBI
13	Chindo BA, Ya'u J, Danjuma NM, Okhale SE, Gamaniel KS and Becker A: Behavioral and anticonvulsant effects of the standardized extract of Ficus platyphylla stem bark. J Ethnopharmacol. 154:351–390. 2014. View Article : Google Scholar : PubMed/NCBI
14	Ngo Bum E, Taiwe GS, Moto FC, Ngoupaye GT, Nkantchoua GC, Pelanken MM, Rakotonirina SV and Rakotonirina A: Anticonvulsant, anxiolytic and sedative properties of the roots of Nauclea latifolia smith in mice. Epilepsy Behav. 15:434–440. 2009. View Article : Google Scholar : PubMed/NCBI
15	Malhi SM, Jawed H, Hanif F, Ashraf N, Zubair F, Siddiqui BS, Begum S, Kabir N and Simjee S: Modulation of c-Fos and BDNF protein expression in pentylenetetrazole-kindled mice following the treatment with novel antiepileptic compound HHL-6. Biomed Res Int. 2014:8767122014. View Article : Google Scholar : PubMed/NCBI
16	Hu Y, Liu P, Dai-Hong G, Rahman K, Wang DX, Chen ML and Xie TT: Behavioral and biochemical effects of Kaixin-San, a traditional Chinese medicinal empirical formula. Drug Dev Res. 69:267–271. 2008. View Article : Google Scholar
17	Putnins SI, Griffin ML, Fitzmaurice GM, Dodd DR and Weiss RD: Poor sleep at baseline predicts worse mood outcomes in patients with co-occurring bipolar disorder and substance dependence. J Clin Psychiatry. 73:703–708. 2012. View Article : Google Scholar : PubMed/NCBI
18	Uzun S, Kozumplik O, Jakovljević M and Sedić B: Side effects of treatment with benzodiazepines. Psychiatria Danubina. 22:90–93. 2010.PubMed/NCBI
19	Karmann AJ, Kundermann B and Lautenbacher S: Sleep deprivation and pain: A review of the newest literature. Schmerz. 28:141–146. 2014.(In German). View Article : Google Scholar : PubMed/NCBI
20	Monti JM, BaHammam AS, Pandi-Perumal SR, Bromundt V, Spence DW, Cardinali DP and Brown GM: Sleep and circadian rhythm dysregulation in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 43:209–216. 2013. View Article : Google Scholar : PubMed/NCBI
21	Roecker AJ, Mercer SP, Schreier JD, Cox CD, Fraley ME, Steen JT, Lemaire W, Bruno JG, Harrell CM, Garson SL, et al: Discovery of 5′-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2′:5′,3′-terpyridine-3′-carboxamide (MK-1064): A selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia. Chem Med Chem. 9:311–322. 2014. View Article : Google Scholar : PubMed/NCBI
22	van Swinderen B and Kottler B: Explaining general anesthesia: A two-step hypothesis linking sleep circuits and the synaptic release machinery. Bioessays. 36:372–381. 2014. View Article : Google Scholar : PubMed/NCBI
23	Salih MA and Mustafa AA: A substance in broad beans (Vicia faba) is protective against experimentally induced convulsions in mice. Epilepsy Behav. 12:25–29. 2008. View Article : Google Scholar : PubMed/NCBI
24	Borbély AA, Neuhaus HU and Tobler I: Effect of p-chlorophenylalanine and tryptophan on sleep, EEG and motor activity in the rat. Behav Brain Res. 2:1–22. 1981. View Article : Google Scholar : PubMed/NCBI
25	Gianotti M, Botta M, Brough S, Carletti R, Castiglioni E, Corti C, Dal-Cin M, Fratte S Delle, Korajac D, Lovric M, et al: Novel spirotetracyclic zwitterionic dual H-1/5-HT2A receptor antagonists for the treatment of sleep disorders. J Med Chem. 53:7778–7795. 2010. View Article : Google Scholar : PubMed/NCBI
26	Dugovic C: Role of serotonin in sleep mechanisms. Rev Neurol (Paris). 157:S16–S19. 2001.PubMed/NCBI
27	Ruiz FS, Andersen ML, Martins RC, Zager A, Lopes JD and Tufik S: Immune alterations after selective rapid eye movement or total sleep deprivation in healthy male volunteers. Innate Immunity. 18:44–54. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zhao Q, Peng C, Wu X, Chen Y, Wang C and You Z: Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats. Neurobiol Dis. 68:57–65. 2014. View Article : Google Scholar : PubMed/NCBI
29	Müller N: Role of the cytokine network in the CNS and psychic disorders. Nervenarzt. 68:11–20. 1997.(In German). PubMed/NCBI
30	Patterson ZR and Holahan MR: Understanding the neuroinflammatory response following concussion to develop treatment strategies. Front Cell Neurosci. 6:582012. View Article : Google Scholar : PubMed/NCBI
31	Torabi-Nami M, Nasehi M and Zarrindast M-R: Sleep loss and the brain vulnerability to neurodegeneration: Behavioral, biochemical and neuro-histopathological observations in a rat model. Excli Journal. 12:347–372. 2013.PubMed/NCBI