Effects of tenuifolin on rest/wake behaviour in zebrafish

Chen,Zi‑Wen; Peng,Chao‑Bao; Pei,Zhong; Zhang,Meng‑Ruo; Yun,Tian‑Chan; Yang,Zhi‑Min; Xu,Fu‑Ping

doi:10.3892/etm.2020.8476

Effects of tenuifolin on rest/wake behaviour in zebrafish

Authors:
- Zi‑Wen Chen
- Chao‑Bao Peng
- Zhong Pei
- Meng‑Ruo Zhang
- Tian‑Chan Yun
- Zhi‑Min Yang
- Fu‑Ping Xu
View Affiliations

Affiliations: Health Construction Administration Center, The Second Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Traditional Chinese Medicine, Zhaoqing Hospital of Traditional Chinese Medicine, Zhaoqing, Guangdong 526020, P.R. China, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Health Construction Administration Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
Published online on: January 28, 2020 https://doi.org/10.3892/etm.2020.8476
Pages: 2326-2334
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Insomnia is a common sleep disorder with a high prevalence and substantial adverse consequences. There is growing interest in identifying novel therapeutics from herbal medicine. Tenuifolin is a major constituent of the well‑known anti‑insomnia herb Radix Polygala. The present study investigated the neural activity in response to tenuifolin during rest/wake behaviour in zebrafish and identified the potential biological signalling pathways involved. An automatic video tracking system was used to monitor the behavioural response of zebrafish larvae for 24 h after treatment with tenuifolin. In total, six rest/wake parameters were measured and visualized with a behavioural fingerprint. Time series analysis was conducted by averaging the total rest and waking activity in 10 min intervals. A correlation analysis was performed between tenuifolin and well‑known compounds to analyse the underlying biological signalling pathways. Reverse transcription‑quantitative PCR was also performed to detect the effects of tenuifolin on the transcription of interesting genes associated with the signalling pathways that were potentially involved. The present results suggested tenuifolin significantly increased the total rest time during the dark phase, with a slight effect on the waking activity in zebrafish larvae. This behavioural phenotype induced by tenuifolin is similar to that of selective serotonin reuptake inhibitors and gamma‑aminobutyric acid (GABA) agonists. Furthermore, the expression levels of GABA transporter 1 were significantly increased after tenuifolin treatment. No significant difference was determined in other associated genes in untreated control and tenuifolin‑treated larvae. The present results suggested that tenuifolin caused sleep‑promoting activity in zebrafish and that these effects may be mediated by the serotoninergic systems and the GABAergic systems.

View Figures

View References

1	Roth T: Insomnia: Definition, prevalence, etiology, and consequences. J Clin Sleep Med. 3 (Suppl 5):S7–S10. 2007. View Article : Google Scholar : PubMed/NCBI
2	Léger D, Morin CM, Uchiyama M, Hakimi Z, Cure S and Walsh JK: Chronic insomnia, quality-of-life, and utility scores: Comparison with good sleepers in a cross-sectional international survey. Sleep Med. 13:43–51. 2012. View Article : Google Scholar : PubMed/NCBI
3	Asnis GM, Thomas M and Henderson MA: Pharmacotherapy treatment options for insomnia: A primer for clinicians. Int J Mol Sci. 17:E502015. View Article : Google Scholar : PubMed/NCBI
4	Swinney DC: The contribution of mechanistic understanding to phenotypic screening for first-in-class medicines. J Biomol Screen. 18:1186–1192. 2013. View Article : Google Scholar : PubMed/NCBI
5	Ek F, Malo M, Åberg Andersson M, Wedding C, Kronborg J, Svensson P, Waters S, Petersson P and Olsson R: Behavioral analysis of dopaminergic activation in zebrafish and rats reveals similar phenotypes. ACS Chem Neurosci. 7:633–646. 2016. View Article : Google Scholar : PubMed/NCBI
6	Ellis LD and Soanes KH: A larval zebrafish model of bipolar disorder as a screening platform for neuro-therapeutics. Behav Brain Res. 233:450–457. 2012. View Article : Google Scholar : PubMed/NCBI
7	Levitas-Djerbi T and Appelbaum L: Modeling sleep and neuropsychiatric disorders in zebrafish. Curr Opin Neurobiol. 44:89–93. 2017. View Article : Google Scholar : PubMed/NCBI
8	Zhdanova IV, Wang SY, Leclair OU and Danilova NP: Melatonin promotes sleep-like state in zebrafish. Brain Res. 903:263–268. 2001. View Article : Google Scholar : PubMed/NCBI
9	Blank M, Guerim LD, Cordeiro RF and Vianna MR: A one-trial inhibitory avoidance task to zebrafish: Rapid acquisition of an NMDA-dependent long-term memory. Neurobiol Learn Mem. 92:529–534. 2009. View Article : Google Scholar : PubMed/NCBI
10	Pather S and Gerlai R: Shuttle box learning in zebrafish (Danio rerio). Behav Brain Res. 196:323–327. 2009. View Article : Google Scholar : PubMed/NCBI
11	Egan RJ, Bergner CL, Hart PC, Cachat JM, Canavello PR, Elegante MF, Elkhayat SI, Bartels BK, Tien AK, Tien DH, et al: Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish. Behav Brain Res. 205:38–44. 2009. View Article : Google Scholar : PubMed/NCBI
12	Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT and Schier AF: Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science. 327:348–351. 2010. View Article : Google Scholar : PubMed/NCBI
13	Sánchez-Ortuño MM, Bélanger L, Ivers H, LeBlanc M and Morin CM: The use of natural products for sleep: A common practice? Sleep Med. 10:982–987. 2009. View Article : Google Scholar : PubMed/NCBI
14	Wing YK: Herbal treatment of insomnia. Hong Kong Med J. 7:392–402. 2001.PubMed/NCBI
15	Cao Q, Jiang Y, Cui SY, Tu PF, Chen YM, Ma XL, Cui XY, Huang YL, Ding H, Song JZ, et al: Tenuifolin, a saponin derived from Radix Polygalae, exhibits sleep-enhancing effects in mice. Phytomedicine. 23:1797–1805. 2016. View Article : Google Scholar : PubMed/NCBI
16	Ling Y, Li Z, Chen M, Sun Z, Fan M and Huang C: Analysis and detection of the chemical constituents of Radix Polygalae and their metabolites in rats after oral administration by ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. J Pharm Biomed Anal. 85:1–13. 2013. View Article : Google Scholar : PubMed/NCBI
17	Cheng MC, Li CY, Ko HC, Ko FN, Lin YL and Wu TS: Antidepressant principles of the roots of Polygala tenuifolia. J Nat Prod. 69:1305–1309. 2006. View Article : Google Scholar : PubMed/NCBI
18	Shin EJ, Oh KW, Kim KW, Kwon YS, Jhoo JH, Jhoo WK, Cha JY, Lim YK, Kim IS and Kim HC: Attenuation of cocaine-induced conditioned place preference by Polygala tenuifolia root extract. Life Sci. 75:2751–2764. 2004. View Article : Google Scholar : PubMed/NCBI
19	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
20	Lee CI, Han JY, Hong JT and Oh KW: 3,4,5-Trimethoxycinnamic acid (TMCA), one of the constituents of Polygalae Radix enhances pentobarbital-induced sleeping behaviors via GABAAergic systems in mice. Arch Pharm Res. 36:1244–1251. 2013. View Article : Google Scholar : PubMed/NCBI
21	Ma B, Li X, Li J, Zhang Q, Liu Y, Yang X, Sun J, Yao D, Liu L, Liu X and Ying H: Quantitative analysis of tenuifolin concentrations in rat plasma and tissue using LC-MS/MS: application to pharmacokinetic and tissue distribution study. J Pharm Biomed Anal. 88:191–200. 2014. View Article : Google Scholar : PubMed/NCBI
22	Wallace CK, Bright LA, Marx JO, Andersen RP, Mullins MC and Carty AJ: Effectiveness of rapid cooling as a method of euthanasia for young zebrafish (Danio rerio). J Am Assoc Lab Anim Sci. 57:58–63. 2018.PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Wang YN, Hou YY, Sun MZ, Zhang CY, Bai G, Zhao X and Feng XZ: Behavioural screening of zebrafish using neuroactive traditional Chinese medicine prescriptions and biological targets. Sci Rep. 4:53112014. View Article : Google Scholar : PubMed/NCBI
25	Melancon MO, Lorrain D and Dionne IJ: Exercise and sleep in aging: Emphasis on serotonin. Pathol Biol (Paris). 62:276–283. 2014. 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	Heym J, Steinfels GF and Jacobs BL: Activity of serotonin-containing neurons in the nucleus raphe pallidus of freely moving cats. Brain Res. 251:259–276. 1982. View Article : Google Scholar : PubMed/NCBI
28	Pastel RH and Fernstrom JD: Short-term effects of fluoxetine and trifluoromethylphenylpiperazine on electroencephalographic sleep in the rat. Brain Res. 436:92–102. 1987. View Article : Google Scholar : PubMed/NCBI
29	Sommerfelt L and Ursin R: Behavioral, sleep-waking and EEG power spectral effects following the two specific 5-HT uptake inhibitors zimeldine and alaproclate in cats. Behav Brain Res. 45:105–115. 1991. View Article : Google Scholar : PubMed/NCBI
30	Weber M, Talmon S, Schulze I, Boeddinghaus C, Gross G, Schoemaker H and Wicke KM: Running wheel activity is sensitive to acute treatment with selective inhibitors for either serotonin or norepinephrine reuptake. Psychopharmacology (Berl). 203:753–762. 2009. View Article : Google Scholar : PubMed/NCBI
31	Airhart MJ, Lee DH, Wilson TD, Miller BE, Miller MN and Skalko RG: Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC). Neurotoxicol Teratol. 29:652–664. 2007. View Article : Google Scholar : PubMed/NCBI
32	Jones BE: Neurobiology of waking and sleeping. Handb Clin Neurol. 98:131–149. 2011. View Article : Google Scholar : PubMed/NCBI
33	Holst SC and Landolt HP: Sleep-Wake Neurochemistry. Sleep Med Clin. 13:137–146. 2018. View Article : Google Scholar : PubMed/NCBI
34	Richey SM and Krystal AD: Pharmacological advances in the treatment of insomnia. Curr Pharm Des. 17:1471–1475. 2011. View Article : Google Scholar : PubMed/NCBI
35	Martin DL and Rimvall K: Regulation of gamma-aminobutyric acid synthesis in the brain. J Neurochem. 60:395–407. 1993. View Article : Google Scholar : PubMed/NCBI
36	Soghomonian JJ and Martin DL: Two isoforms of glutamate decarboxylase: Why? Trends Pharmacol Sci. 19:500–505. 1998. View Article : Google Scholar : PubMed/NCBI
37	Hortopan GA, Dinday MT and Baraban SC: Spontaneous seizures and altered gene expression in GABA signaling pathways in a mind bomb mutant zebrafish. The J Neurosci. 30:13718–13728. 2010. View Article : Google Scholar : PubMed/NCBI
38	Kang TC, Kim HS, Seo MO, Park SK, Kwon HY, Kang JH and Won MH: The changes in the expressions of gamma-aminobutyric acid transporters in the gerbil hippocampal complex following spontaneous seizure. Neurosci Lett. 310:29–32. 2001. View Article : Google Scholar : PubMed/NCBI
39	Meldrum BS and Rogawski MA: Molecular targets for antiepileptic drug development. Neurotherapeutics. 4:18–61. 2007. View Article : Google Scholar : PubMed/NCBI
40	Chen NH, Reith ME and Quick MW: Synaptic uptake and beyond: The sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch. 447:519–531. 2004. View Article : Google Scholar : PubMed/NCBI