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Journal of Traditional Chinese Medicine >

2022 , Vol. 42 >Issue 6: 956 - 964

DOI: https://doi.org/10.19852/j.cnki.jtcm.20220902.001

Research Articles

Compound Gaoziban tablet (复方高滋斑片) alleviates depression via toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway

  • Xinshuang ZOU ,
  • Lei SHI ,
  • Hailong YIN ,
  • Haiping LI ,
  • Mengheng WANG ,
  • Wanci SONG ,
  • Laichun LUO ,
  • Hezhen WU ,
  • Yanfang YANG ,
  • Junfeng ZAN ,
  • Yanwen LIU ,
  • Hanxiong DAN ,
  • Qiang YIN ,
  • Pengtao YOU
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  • 1 Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Hubei 430065, China
    2 Xinjiang Uygur Pharmaceutical Co., Ltd., Urumqi 830001, China
YOU Pengtao, Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Hubei 430065, China, tptyou@hbtcm.edu.cn,Telephone: +86-27-88920834
YIN Qiang, Xinjiang Uygur Pharmaceutical Co., Ltd., Urumqi 830001, China, yinqiang@renfu.com.cn;

Received date: 2021-10-14

  Accepted date: 2022-01-11

  Online published: 2022-09-02

Supported by

Scientific Research Project of Education Department of Hubei Province: Synthesis and Anti-hepatocellular Carcinoma Effect of Novel NMT1 Inhibitors(D20192003)

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Abstract

OBJECTIVE: To evaluate the effect of compound Gaoziban tablet (复方高滋斑片, CGZBT) on depression, and to investigate the underlying mechanism.

METHODS: The components of CGZBT were analysed by high-performance liquid chromatography. Then, we assessed the effects of varying doses of CGZBT on an established chronic unpredictable mild stress (CUMS) model in rats. Whether animals were depressed was evaluated by sucrose preference test, open field test and forced swimming test. Neurotransmitters of hippocampus were detected by liquid chromatography-mass spec-trometry. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay. Expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phospho-nuclear factor-kappa B (p-NF-κB), cyclooxygenase-2 (COX-2), ionized calcium binding adapter molecule-1 (IBA-1) were assessed by immunohistochemical staining and western blotting.

RESULTS: Eight compounds were identified from CGZBT, moreover, our results showed that CGZBT effectively reversed the CUMS-induced decrease in sucrose preference, shortened the movement distance and prolonged immobility time. CGZBT significantly increased levels of 5-hydroxytryptamine, dopamine, norepinephrine, 5-hydroxyindoleacetic acid levels, and reduced the expression of TNF-α, IL-1β, IL-6, yet increased IL-4 and IL-10. Furthermore, the expressions of TLR4, MyD88, COX-2, p-NF-κB and IBA-1 in hippocampus were effectively reversed after treatment with CGZBT.

CONCLUSIONS: These results indicated that CGZBT could, at least in part, alleviate depression induced by CUMS via the TLR4/MyD88/NF-κB pathway, suggesting its potential as an antidepressant drug.

Key words： depression; toll-like receptor 4; myeloid differentiation factor 88; NF-kappa B; chronic unpredictable mild stress; compound Gaoziban tablet

Cite this article

Xinshuang ZOU , Lei SHI , Hailong YIN , Haiping LI , Mengheng WANG , Wanci SONG , Laichun LUO , Hezhen WU , Yanfang YANG , Junfeng ZAN , Yanwen LIU , Hanxiong DAN , Qiang YIN , Pengtao YOU . Compound Gaoziban tablet (复方高滋斑片) alleviates depression via toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway[J]. Journal of Traditional Chinese Medicine, 2022 , 42(6) : 956 -964 . DOI: 10.19852/j.cnki.jtcm.20220902.001

References

[1] Christensen GT, Maartensson S, Osler M. The association between depression and mortality - a comparison of survey- and register-based measures of depression. J Affect Disord 2017; 210: 111-4.
[2] Lee EH, Han PL. Reciprocal interactions across and within multiple levels of monoamine and cortico-limbic systems in stress-induced depression: a systematic review. Neurosci Biobehav Rev 2019; 101: 13-31.
[3] Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24-31.
[4] Yazir Y, Utkan T, Gacar N, Aricioglu F. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress. Physiol Behav 2015; 138: 297-304.
[5] Fang H, Wu Y, Huang X, et al. Toll-like receptor 4 (TLR4) is essential for Hsp70-like protein 1 (HSP70L1) to activate dendritic cells and induce Th1 response. J Biol Chem 2011; 138: 297-304.
[6] Zhao M, Zhou A, Xu L, Zhang X. The role of TLR4-mediated PTEN/PI3K/AKT/NF-kappaB signaling pathway in neuro-inflammation in hippocampal neurons. Neuroscience 2014; 269: 93-101.
[7] Hung YY, Kang HY, Huang KW, Huang TL. Association between toll-like receptors expression and major depressive disorder. Psychiatry Res 2014; 220: 283-6.
[8] Wang L, Chen J. Progress in studies on TLR4 signaling pathway and major depressive disorder. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017; 42: 725-9.
[9] Zhou J, Cai H, Duan Y, et al. Research progress on antidepressant effects of Sini San based on three progressive levels of "single herb, herb-pair, and complicated Chinese herbal formula". Zhong Guo Zhong Yao Za Zhi 2018; 43: 46-51.
[10] Zhang X, Tian JS, Liu H, Qin XM. Progress of new antidepressant drugs development. Zhong Guo Zhong Yao Za Zhi 2017; 42: 29-33.
[11] Pharmacopoeia Committee MoH, PRC. Drug standards of the Ministry of health of the people's Republic of China-Uyghur medicine volume. Urumqi: Xinjiang Science and Technology and Health Publishing House, 1998: 171-2.
[12] Wang WH, Wu XL, Xia P, Li H. Study on the content changes of 5 constituents in fructus periuae before and after stir-frying by HPLC. Zhong Guo Yao Shi 2020; 23: 1855-8.
[13] Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrie P. Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry 2004; 9: 278-86, 224.
[14] Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997; 134: 319-29.
[15] Wang C, He L, Yan M, Zheng GY, Liu XY. Effects of polyprenols from pine needles of Pinus massoniana on ameliorating cognitive impairment in a D-galactose-induced mouse model. Age (Dordr) 2014; 36: 9676.
[16] Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 1997; 8: 523-32.
[17] Mou XJ, Ming H, Xu LS, et al. Active substance fractions and effects of Shugan Hewei Tang on hippocampal meurotransmitters in rat model of chronic stress-induced depression. Zhong Guo Zhong Yao Za Zhi 2019; 44: 526-34.
[18] Lu P, Mamiya T, Lu L, et al. Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin induced by repeated methamphetamine treatment. Behav Brain Res 2010; 207: 387-93.
[19] Khan H, Perviz S, Sureda A, Nabavi SM, Tejada S. Current standing of plant derived flavonoids as an antidepressant. Food Chem Toxicol 2018; 119: 176-88.
[20] Surget A, Saxe M, Leman S, et al. Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol Psychiatry 2008; 64: 293-301.
[21] Liu Y, Zhao J, Guo W. Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders. Front Psychol 2018; 9: 2201.
[22] Cheng J, Dong S, Yi L, Geng D, Liu Q. Magnolol abrogates chronic mild stress-induced depressive-like behaviors by inhibiting neuroinflammation and oxidative stress in the prefrontal cortex of mice. Int Immunopharmacol 2018; 59: 61-7.
[23] Dowlati Y, Herrmann N, Swardfager W, et al. A Meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67: 446-57.
[24] Ma M, Ren Q, Yang C, et al. Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation. Psychopharmacology (Berl) 2017; 234: 525-33.
[25] Zhou XY, Zhang F, Hu XT, et al. Depression can be prevented by astaxanthin through inhibition of hippocampal inflammation in diabetic mice. Brain Res 2017; 1657: 262-8.
[26] Hung YY, Lin CC, Kang HY, Huang TL. TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder. Brain Behav Immun 2017; 59: 265-72.
[27] Carvalho AF, Macedo DS, Goulia P, Hyphantis TN. N-acetylcysteine augmentation to tranylcypromine in treatment-resistant major depression. J Clin Psychopharmacol 2013; 33: 719-20.
[28] Kang JW, Koh EJ, Lee SM. Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll-like receptor signaling pathway. J Pineal Res 2011; 50: 403-11.
[29] Hajebrahimi B, Bagheri M, Hassanshahi G, et al. The adapter proteins of TLRs, TRIF and MYD88, are upregulated in depressed individuals. Int J Psychiatry Clin Pract 2014; 18: 41-4.
[30] Qu H, Liu R, Chen J, Zheng L, Chen R. Aerobic exercise inhibits CUMS-depressed mice hippocampal inflammatory response via activating hippocampal miR-223/TLR4/MyD88-NF-kappa B pathway. Int J Environ Res Public Health 2020; 17: 2676.
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