Shuyu capsules relieve liver‑qi depression by regulating ERK‑CREB‑BDNF signal pathway in central nervous system of rat

Wang,Hongyan; Zhang,Yingquan; Li,Helou; Zeng,Wei; Qiao,Mingqi

doi:10.3892/etm.2017.5125

Shuyu capsules relieve liver‑qi depression by regulating ERK‑CREB‑BDNF signal pathway in central nervous system of rat

Authors:
- Hongyan Wang
- Yingquan Zhang
- Helou Li
- Wei Zeng
- Mingqi Qiao
View Affiliations

Affiliations: Department of Traditional Chinese Medicine, Taishan Medical University, Tai'an, Shandong 271000, P.R. China, Department of Internal Medicine, The Hospital of Traditional Chinese Medicine of Tai'an, Tai'an, Shandong 271000, P.R. China, Department of Laboratory, Taishan Medical University, Tai'an, Shandong 271000, P.R. China, Department of Cardiology, Taishan Medical University, Tai'an, Shandong 271000, P.R. China, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/etm.2017.5125
Pages: 4831-4838
Copyright: © Wang 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

The purpose of this study was to investigate the possible therapeutic mechanism of Shuyu capsules in liver‑qi depression. Liver‑qi depression rats were prepared based on chronic unpredictable mild stress (CUMS) and delayed constraint. Rats were gavaged with Shuyu capsule, fluoxetine, Radix Bupleuri and Radix Paeoniae Alba to constrct rat models. Body weight test, sucrose preference test and open‑field test were applied to test rat models. Western blot analysis and quantitative real‑time PCR was applied to determine the relative expression of extracellular signal‑regulated protein kinase (ERK), cyclic AMP response element binding protein (CREB) and brain‑derived neurotrophic factor (BDNF) in hippocampus and frontal lobe tissues. ELISA was used to detect the content of BDNF in serum. Body weight, sugar intake and total distance were significantly decreased in depression group compared with control. The four drugs significantly increased levels of these factors. Compared with control group, ERK, CREB and BDNF expression were significantly decreased in depression group in both hippocampus and frontal lobe tissues at both mRNA and protein level. Shuyu capsule and fluoxetine group showed a significant increase in the expression of ERK, CREB and BDNF at mRNA, p‑ERK and p‑BDNF at protein level. Compared with Radix Paeoniae Alba, Radix Bupleuri were better in the rescue of ERK, CREB and BDNF expression. In conclusion, the pathogenesis of liver‑qi depression associated with lower expression of ERK, CREB and BDNF in hippocampus and frontal. Shuyu capsule and main constitution alleviated the depressive‑like behaviors and reversed the disruptions of the p‑ERK, p‑CREB and BDNF in stressed rats.

View Figures

View References

1	Zandio M, Ferrín M and Cuesta MJ: Neurobiology of depression. An Sist Sanit Navar. 25 Suppl 3:43–62. 2002.(In Spanish). PubMed/NCBI
2	Bremner JD, Vythilingam M, Vermetten E, Vaccarino V and Charney DS: Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. Am J Psychiatry. 161:637–645. 2004. View Article : Google Scholar : PubMed/NCBI
3	Marsden WN: Synaptic plasticity in depression: Molecular, cellular and functional correlates. Prog Neuropsychopharmacol Biol Psychiatry. 43:168–184. 2013. View Article : Google Scholar : PubMed/NCBI
4	Kratz AL, Ehde DM and Bombardier CH: Affective mediators of a physical activity intervention for depression in multiple sclerosis. Rehabil Psychol. 59:57–67. 2014. View Article : Google Scholar : PubMed/NCBI
5	Qi X, Lin W, Li J, Li H, Wang W, Wang D and Sun M: Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol Dis. 31:278–285. 2008. View Article : Google Scholar : PubMed/NCBI
6	Alboni S, Benatti C, Capone G, Corsini D, Caggia F, Tascedda F, Mendlewicz J and Brunello N: Time-dependent effects of escitalopram on brain derived neurotrophic factor (BDNF) and neuroplasticity related targets in the central nervous system of rats. Eur J Pharmacol. 643:180–187. 2010. View Article : Google Scholar : PubMed/NCBI
7	Kumamaru E, Numakawa T, Adachi N, Yagasaki Y, Izumi A, Niyaz M, Kudo M and Kunugi H: Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase. Mol Endocrinol. 22:546–558. 2008. View Article : Google Scholar : PubMed/NCBI
8	Xu H, Richardson Steven J and Li XM: Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus. Neuropsychopharmacology. 28:53–62. 2003. View Article : Google Scholar : PubMed/NCBI
9	Bilecki W, Wawrzczak-Bargiela A and Przewlocki R: Activation of AP-1 and CRE-dependent gene expression via mu-opioid receptor. J Neurochem. 90:874–882. 2004. View Article : Google Scholar : PubMed/NCBI
10	Walters CL, Cleck JN, Kuo YC and Blendy JA: Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron. 46:933–943. 2005. View Article : Google Scholar : PubMed/NCBI
11	Ligeza A, Wawrzczak-Bargiela A, Kaminska D, Korostynski M and Przewlocki R: Regulation of ERK1/2 phosphorylation by acute and chronic morphine - implications for the role of cAMP-responsive element binding factor (CREB)-dependent and Ets-like protein-1 (Elk-1)-dependent transcription; small interfering RNA-based strategy. FEBS J. 275:3836–3849. 2008. View Article : Google Scholar : PubMed/NCBI
12	Tiraboschi E, Tardito D, Kasahara J, Moraschi S, Pruneri P, Gennarelli M, Racagni G and Popoli M: Selective phosphorylation of nuclear CREB by fluoxetine is linked to activation of CaM kinase IV and MAP kinase cascades. Neuropsychopharmacology. 29:1831–1840. 2004. View Article : Google Scholar : PubMed/NCBI
13	Enjeti AK, D'Crus A, Melville K, Verrills NM and Rowlings P: A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia. Anticancer Drugs. 27:560–568. 2016. View Article : Google Scholar : PubMed/NCBI
14	Li F, Feng J, Gao D, Wang J, Song C, Wei S and Qiao M: Shuyu capsules relieve premenstrual syndrome depression by reducing 5-HT3AR and 5-HT3BR expression in the rat brain. Neural Plast. 2016:79507812016. View Article : Google Scholar : PubMed/NCBI
15	Moriyama Y, Takagi N and Tanonaka K: Intravenous injection of neural progenitor cells improved depression-like behavior after cerebral ischemia. Transl Psychiatry. 1:e292011. View Article : Google Scholar : PubMed/NCBI
16	Zhu X, Li T, Peng S, Ma X, Chen X and Zhang X: Maternal deprivation-caused behavioral abnormalities in adult rats relate to a non-methylation-regulated D2 receptor levels in the nucleus accumbens. Behav Brain Res. 209:281–288. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhang L, Luo J, Zhang M, Yao W, Ma X and Yu SY: Effects of curcumin on chronic, unpredictable, mild, stress-induced depressive-like behaviour and structural plasticity in the lateral amygdala of rats. Int J Neuropsychopharmacol. 17:793–806. 2014. View Article : Google Scholar : PubMed/NCBI
18	Wang SS, Wang YG, Chen HY, Wu ZP and Xie HG: Expression of genes encoding cytokines and corticotropin releasing factor are altered by citalopram in the hypothalamus of post-stroke depression rats. Neuro Endocrinol Lett. 34:773–779. 2013.PubMed/NCBI
19	Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR and Duman RS: Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry. 62:496–504. 2007. View Article : Google Scholar : PubMed/NCBI
20	Taksande BG, Faldu DS, Dixit MP, Sakaria JN, Aglawe MM, Umekar MJ and Kotagale NR: Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice. Eur J Pharmacol. 720:115–120. 2013. View Article : Google Scholar : PubMed/NCBI
21	Tsunoda M, Sugaya C, Sugiura Y, Nagai Y and Sakanishi K: Safety evaluation of self-assembling peptide gel after intracranial administration to rats using the open field test. Biol Pharm Bull. 39:1419–1423. 2016. View Article : Google Scholar : PubMed/NCBI
22	Szasz BK, Mike A, Karoly R, Gerevich Z, Illes P, Vizi ES and Kiss JP: Direct inhibitory effect of fluoxetine on N-methyl-D-aspartate receptors in the central nervous system. Biol Psychiatry. 62:1303–1309. 2007. View Article : Google Scholar : PubMed/NCBI
23	Wang HN, Wang L, Zhang RG, Chen YC, Liu L, Gao F, Nie H, Hou WG, Peng ZW and Tan Q: Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: The role of the endocannabinoid system. J Psychiatr Res. 51:79–87. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wu HF, Zhu CH and Guo JY: Effect of ginsenoside Rg1 on behaviors and hippocampal amino acids in depressive-like rats. Zhongguo Zhong Yao Za Zhi. 37:3117–3121. 2012.(In Chinese). PubMed/NCBI
25	McEwen BS: Stress and hippocampal plasticity. Annu Rev Neurosci. 22:105–122. 1999. View Article : Google Scholar : PubMed/NCBI
26	Fu AK, Hung KW, Huang H, Gu S, Shen Y, Cheng EY, Ip FC, Huang X, Fu WY and Ip NY: Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease. Proc Natl Acad Sci USA. 111:9959–9964. 2014. View Article : Google Scholar : PubMed/NCBI
27	Dudkin KN, Chueva IV and Makarov FN: The role of the prefrontal and parietal cortex in learning and memory in monkeys. Ross Fiziol Zh Im I M Sechenova. 86:1458–1470. 2000.(In Russian). PubMed/NCBI
28	Drevets WC: Functional neuroimaging studies of depression: The anatomy of melancholia. Annu Rev Med. 49:341–361. 1998. View Article : Google Scholar : PubMed/NCBI
29	McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, et al: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 1773:1263–1284. 2007. View Article : Google Scholar : PubMed/NCBI
30	Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA and McCubrey JA: Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: Potential targeting for therapeutic intervention. Leukemia. 17:1263–1293. 2003. View Article : Google Scholar : PubMed/NCBI
31	Mantamadiotis T, Lemberger T, Bleckmann SC, Kern H, Kretz O, Villalba Martin A, Tronche F, Kellendonk C, Gau D, Kapfhammer J, et al: Disruption of CREB function in brain leads to neurodegeneration. Nat Genet. 31:47–54. 2002. View Article : Google Scholar : PubMed/NCBI
32	Lonze BE and Ginty DD: Function and regulation of CREB family transcription factors in the nervous system. Neuron. 35:605–623. 2002. View Article : Google Scholar : PubMed/NCBI
33	Yiu AP, Mercaldo V, Yan C, Richards B, Rashid AJ, Hsiang HL, Pressey J, Mahadevan V, Tran MM, Kushner SA, et al: Neurons are recruited to a memory trace based on relative neuronal excitability immediately before training. Neuron. 83:722–735. 2014. View Article : Google Scholar : PubMed/NCBI
34	Hetman M and Gozdz A: Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. Eur J Biochem. 271:2050–2055. 2004. View Article : Google Scholar : PubMed/NCBI
35	Sun ZG, Huang QZ, Xu CY and Chen LP: Effects of shuyu ningxln recipe on the praxiology and the expressions of hippocampal BDNF and trkB of model rats with chronic stress-induced depression. Zhongguo Zhong Xi Yi Jie He Za Zhi. 33:370–375. 2013.(In Chinese). PubMed/NCBI