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The extract based on the Kampo formula daikenchuto (Da Jian Zhong Tang) induces Bdnf expression and has neurotrophic effects in cultured cortical neurons

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Abstract

Reductions in brain-derived neurotrophic factor (BDNF) expression levels have been reported in the brains of patients with neurological disorders such as Alzheimer’s disease. Therefore, upregulating BDNF and preventing its decline in the diseased brain could help ameliorate neurological dysfunctions. Accordingly, we sought to discover agents that increase Bdnf expression in neurons. Here, we screened a library of 42 Kampo extracts to identify those with the ability to induce Bdnf expression in cultured cortical neurons. Among the active extracts identified in the screen, we focused on the extract based on the Kampo formula daikenchuto. The extract of daikenchuto in the library used in this study was prepared using the mixture of Zingiberis Rhizoma Processum (ZIN), Zanthoxyli Piperiti Pericarpium (ZAN), and Ginseng Radix (GIN) without Koi. In this study, we defined DKT as the mixture of ZIN, ZAN, and GIN without Koi (DKT extract means the extract prepared from the mixture of ZIN, ZAN, and GIN without Koi). DKT extract significantly increased endogenous Bdnf expression by mediated, at least in part, via Ca2+ signaling involving L-type voltage-dependent Ca2+ channels in cultured cortical neurons. Furthermore, DKT extract significantly improved the survival of cultured cortical neurons and increased neurite complexity in immature neurons. Taken together, our findings suggest that DKT extract induces Bdnf expression and has a neurotrophic effect in neurons. Because BDNF inducers are expected to have therapeutic potential for neurological disorders, re-positioning of Kampo formulations such as daikenchuto may lead to clinical application in diseases associated with reduced BDNF in the brain.

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References

  1. Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14:7–23. https://doi.org/10.1038/nrn3379

    Article  CAS  PubMed  Google Scholar 

  2. Miranda M, Morici JF, Zanoni MB, Bekinschtein P (2019) Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci 13:363. https://doi.org/10.3389/fncel.2019.00363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lima Giacobbo B, Doorduin J, Klein HC, Dierckx RAJO, Bromberg E, de Vries EFJ (2019) Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation. Mol Neurobiol 56:3295–3312. https://doi.org/10.1007/s12035-018-1283-6

    Article  CAS  PubMed  Google Scholar 

  4. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50:260–265. https://doi.org/10.1016/S0006-3223(01)01083-6

    Article  CAS  PubMed  Google Scholar 

  5. Molendijk ML, Bus BA, Spinhoven P, Penninx BW, Kenis G, Prickaerts J, Voshaar RC, Elzinga BM (2011) Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Mol Psychiatry 16:1088–1095. https://doi.org/10.1038/mp.2010.98

    Article  CAS  PubMed  Google Scholar 

  6. Buchman AS, Yu L, Boyle PA, Schneider JA, De Jager PL, Bennett DA (2016) Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology 86:735–741. https://doi.org/10.1212/WNL.0000000000002387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fukuchi M, Okuno Y, Nakayama H, Nakano A, Mori H, Mitazaki S, Nakano Y, Toume K, Jo M, Takasaki I, Watanabe K, Shibahara N, Komatsu K, Tabuchi A, Tsuda M (2019) Screening inducers of neuronal BDNF gene transcription using primary cortical cell cultures from BDNF-luciferase transgenic mice. Sci Rep 9:11833. https://doi.org/10.1038/s41598-019-48361-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fukuchi M (2020) Identifying inducers of BDNF gene expression from pharmacologically validated compounds; antipyretic drug dipyrone increases BDNF mRNA in neurons. Biochem Biophys Res Commun 524:957–962. https://doi.org/10.1016/j.bbrc.2020.02.019

    Article  CAS  PubMed  Google Scholar 

  9. Fukuchi M, Tabuchi A, Kuwana Y, Watanabe S, Inoue M, Takasaki I, Izumi H, Tanaka A, Inoue R, Mori H, Komatsu H, Takemori H, Okuno H, Bito H, Tsuda M (2015) Neuromodulatory effect of Gαs- or Gαq-coupled G-protein-coupled receptor on NMDA receptor selectively activates the NMDA receptor/Ca2+/calcineurin/cAMP response element-binding protein-regulated transcriptional coactivator 1 pathway to effectively induce brain-derived neurotrophic factor expression in neurons. J Neurosci 35:5606–5624. https://doi.org/10.1523/JNEUROSCI.3650-14.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fukuchi M, Izumi H, Mori H, Kiyama M, Otsuka S, Maki S, Maehata Y, Tabuchi A, Tsuda M (2017) Visualizing changes in brain-derived neurotrophic factor (BDNF) expression using bioluminescence imaging in living mice. Sci Rep 7:4949. https://doi.org/10.1038/s41598-017-05297-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119:203–210. https://doi.org/10.1016/0022-1759(89)90397-9

    Article  CAS  PubMed  Google Scholar 

  12. Ihara D, Fukuchi M, Honma D, Takasaki I, Ishikawa M, Tabuchi A, Tsuda M (2012) Deltamethrin, a type II pyrethroid insecticide, has neurotrophic effects on neurons with continuous activation of the Bdnf promoter. Neuropharmacology 62:1091–1098. https://doi.org/10.1016/j.neuropharm.2011.10.023

    Article  CAS  PubMed  Google Scholar 

  13. Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ishikawa M, Nishijima N, Shiota J, Sakagami H, Tsuchida K, Mizukoshi M, Fukuchi M, Tsuda M, Tabuchi A (2010) Involvement of the serum response factor coactivator megakaryoblastic leukemia (MKL) in the activin-regulated dendritic complexity of rat cortical neurons. J Biol Chem 285:32734–32743. https://doi.org/10.1074/jbc.M110.118745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ihara D, Fukuchi M, Katakai M, Shinoda Y, Katoh-Semba R, Furuichi T, Ishikawa M, Tabuchi A, Tsuda M (2017) Deltamethrin increases neurite outgrowth in cortical neurons through endogenous BDNF/TrkB pathways. Cell Struct Funct 42:141–148. https://doi.org/10.1247/csf.17015

    Article  CAS  PubMed  Google Scholar 

  16. Meichsner M, Doll T, Reddy D, Weisshaar B, Matus A (1993) The low molecular weight form of microtubule-associated protein 2 is transported into both axons and dendrites. Neuroscience 54:873–880. https://doi.org/10.1016/0306-4522(93)90581-Y

    Article  CAS  PubMed  Google Scholar 

  17. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA (2015) Protective effects of ginseng on neurological disorders. Front Aging Neurosci 7:129. https://doi.org/10.3389/fnagi.2015.00129

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kim HJ, Jung SW, Kim SY, Cho IH, Kim HC, Rhim H, Kim M, Nah SY (2018) Panax ginseng as an adjuvant treatment for Alzheimer’s disease. J Ginseng Res 42:401–411. https://doi.org/10.1016/j.jgr.2017.12.008

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jakaria M, Kim J, Karthivashan G, Park SY, Ganesan P, Choi DK (2019) Emerging signals modulating potential of ginseng and its active compounds focusing on neurodegenerative diseases. J Ginseng Res 43:163–171. https://doi.org/10.1016/j.jgr.2018.01.001

    Article  PubMed  Google Scholar 

  20. Jin Y, Cui R, Zhao L, Fan J, Li B (2019) Mechanisms of Panax ginseng action as an antidepressant. Cell Prolif 52:e12696. https://doi.org/10.1111/cpr.12696

    Article  PubMed  PubMed Central  Google Scholar 

  21. Finkbeiner S (2000) Calcium regulation of the brain-derived neurotrophic factor gene. Cell Mol Life Sci 57:394–401. https://doi.org/10.1007/PL00000701

    Article  CAS  PubMed  Google Scholar 

  22. West AE, Greenberg ME (2011) Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb Perspect Biol 3:a005744. https://doi.org/10.1101/cshperspect.a005744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sun AY, Cheng Y, Sun GY (1992) Kainic acid-induced excitotoxicity in neurons and glial cells. Prog Brain Res 94:271–280. https://doi.org/10.1016/S0079-6123(08)61757-4

    Article  CAS  PubMed  Google Scholar 

  24. Wang Q, Yu S, Simonyi A, Sun GY, Sun AY (2005) Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol 31:3–16. https://doi.org/10.1385/MN:31:1-3:003

    Article  CAS  PubMed  Google Scholar 

  25. Kiefer D, Pantuso T (2003) Panax ginseng. Am Fam Phys 68:1539–1542

    Google Scholar 

  26. Hwang SH, Shin TJ, Choi SH, Cho HJ, Lee BH, Pyo MK, Lee JH, Kang J, Kim HJ, Park CW, Shin HC, Nah SY (2012) Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity. Mol Cells 33:151–162. https://doi.org/10.1007/s10059-012-2216-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Jiang B, Xiong Z, Yang J, Wang W, Wang Y, Hu ZL, Wang F, Chen JG (2012) Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol 166:1872–1887. https://doi.org/10.1111/j.1476-5381.2012.01902.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li F, Wu X, Li J, Niu Q (2016) Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer’s disease model. Mol Med Rep 13:4904–4910. https://doi.org/10.3892/mmr.2016.5103

    Article  CAS  PubMed  Google Scholar 

  29. Hagenston AM, Bading H (2011) Calcium signaling in synapse-to-nucleus communication. Cold Spring Harb Perspect Biol 3:a004564. https://doi.org/10.1101/cshperspect.a004564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ch’ng TH, Uzgil B, Lin P, Avliyakulov NK, O’Dell TJ, Martin KC (2012) Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell 150:207–221. https://doi.org/10.1016/j.cell.2012.05.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nonaka M, Kim R, Fukushima H, Sasaki K, Suzuki K, Okamura M, Ishii Y, Kawashima T, Kamijo S, Takemoto-Kimura S, Okuno H, Kida S, Bito H (2014) Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory. Neuron 84:92–106. https://doi.org/10.1016/j.neuron.2014.08.049

    Article  CAS  PubMed  Google Scholar 

  32. Shieh PB, Hu SC, Bobb K, Timmusk T, Ghosh A (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20:727–740. https://doi.org/10.1016/s0896-6273(00)81011-9

    Article  CAS  PubMed  Google Scholar 

  33. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20:709–726. https://doi.org/10.1016/s0896-6273(00)81010-7

    Article  CAS  PubMed  Google Scholar 

  34. Tabuchi A, Sakaya H, Kisukeda T, Fushiki H, Tsuda M (2002) Involvement of an upstream stimulatory factor as well as cAMP-responsive element-binding protein in the activation of brain-derived neurotrophic factor gene promoter I. J Biol Chem 277:35920–35931. https://doi.org/10.1074/jbc.M204784200

    Article  CAS  PubMed  Google Scholar 

  35. Pruunsild P, Sepp M, Orav E, Koppel I, Timmusk T (2011) Identification of cis-elements and transcription factors regulating neuronal activity-dependent transcription of human BDNF gene. J Neurosci 31:3295–3308. https://doi.org/10.1523/JNEUROSCI.4540-10.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Walton MR, Dragunow I (2000) Is CREB a key to neuronal survival? Trends Neurosci 23:48–53. https://doi.org/10.1016/S0166-2236(99)01500-3

    Article  CAS  PubMed  Google Scholar 

  37. Redmond L, Kashani AH, Ghosh A (2002) Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron 34:999–1010. https://doi.org/10.1016/S0896-6273(02)00737-7

    Article  CAS  PubMed  Google Scholar 

  38. Sakamoto K, Karelina K, Obrietan K (2011) CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem 116:1–9. https://doi.org/10.1111/j.1471-4159.2010.07080.x

    Article  CAS  PubMed  Google Scholar 

  39. Fukuchi M, Kirikoshi Y, Mori A, Eda R, Ihara D, Takasaki I, Tabuchi A, Tsuda M (2014) Excitatory GABA induces BDNF transcription via CRTC1 and phosphorylated CREB-related pathways in immature cortical cells. J Neurochem 131:134–146. https://doi.org/10.1111/jnc.12801

    Article  CAS  PubMed  Google Scholar 

  40. Furukawa Y, Shiga Y, Hanyu N, Hashimoto Y, Mukai H, Nishikawa K, Aoki T (1995) Effect of Chinese herbal medicine on gastrointestinal motility and bowel obstruction. Jpn J Gastroenterol Surg 28:956–960. https://doi.org/10.5833/jjgs.28.956

    Article  Google Scholar 

  41. Kubota K, Mase A, Matsushima H, Fujitsuka N, Yamamoto M, Morine Y, Taketomi A, Kono T, Shimada M (2019) Daikenchuto, a traditional Japanese herbal medicine, promotes colonic transit by inducing a propulsive movement pattern. Neurogastroenterol Motil 31:e13689. https://doi.org/10.1111/nmo.13689

    Article  PubMed  PubMed Central  Google Scholar 

  42. Shi Z, Takeuchi T, Nakanishi Y, Kato T, Beck K, Nagata R, Kageyama T, Ito A, Ohno H, Satoh-Takayama N (2022) A Japanese herbal formula, Daikenchuto, alleviates experimental colitis by reshaping microbial profiles and enhancing group 3 innate lymphoid cells. Front Immunol 13:903459. https://doi.org/10.3389/fimmu.2022.903459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sonali S, Ray B, Ahmed Tousif H, Rathipriya AG, Sunanda T, Mahalakshmi AM, Rungratanawanich W, Essa MM, Qoronfleh MW, Chidambaram SB, Song BJ (2022) Mechanistic insights into the link between gut dysbiosis and major depression: an extensive review. Cells 11:1362. https://doi.org/10.3390/cells11081362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V, Tompkins T (2014) Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil 26:510–520. https://doi.org/10.1111/nmo.12295

    Article  CAS  PubMed  Google Scholar 

  45. Nakamura T, Komai N, Isogami I, Ueno K, Ikegami F, Ono K, Yano S (2006) Memory and learning-enhancing effect of Daikenchuto, a traditional Japanese herbal medicine, in mice. J Nat Med 60:64–67. https://doi.org/10.1007/s11418-005-0012-4

    Article  Google Scholar 

  46. Furukawa-Hibi Y, Nitta A, Ikeda T, Morishita K, Liu W, Ibi D, Alkam T, Nabeshima T, Yamada K (2011) The hydrophobic dipeptide Leu-Ile inhibits immobility induced by repeated forced swimming via the induction of BDNF. Behav Brain Res 220:271–280. https://doi.org/10.1016/j.bbr.2011.02.003

    Article  CAS  PubMed  Google Scholar 

  47. Sawamoto A, Okuyama S, Amakura Y, Yoshimura M, Yamada T, Yokogoshi H, Nakajima M, Furukawa Y (2017) 3,5,6,7,8,3’,4’-Heptamethoxyflavone ameliorates depressive-like behavior and hippocampal neurochemical changes in chronic unpredictable mild stressed mice by regulating the brain-derived neurotrophic factor: Requirement for ERK activation. Int J Mol Sci 18:2133. https://doi.org/10.3390/ijms18102133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fang W, Zhang J, Hong L, Huang W, Dai X, Ye Q, Chen X (2020) Metformin ameliorates stress-induced depression-like behaviors via enhancing the expression of BDNF by activating AMPK/CREB-mediated histone acetylation. J Affect Disord 260:302–313. https://doi.org/10.1016/j.jad.2019.09.013

    Article  CAS  PubMed  Google Scholar 

  49. Forlenza OV, Diniz BS, Teixeira AL, Radanovic M, Talib LL, Rocha NP, Gattaz WF (2015) Lower cerebrospinal fluid concentration of brain-derived neurotrophic factor predicts progression from mild cognitive impairment to Alzheimer’s disease. Neuromol Med 17:326–332. https://doi.org/10.1007/s12017-015-8361-y

    Article  CAS  Google Scholar 

  50. Gao L, Zhang Y, Sterling K, Song W (2022) Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Transl Neurodegener 11:4. https://doi.org/10.1186/s40035-022-00279-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Koike K, Ohno S, Takahashi N, Suzuki N, Nozaki N, Murakami K, Sugiura K, Yamada K, Inoue M (2004) Efficacy of the herbal medicine Unkei-to as an adjunctive treatment to hormone replacement therapy for postmenopausal women with depressive symptoms. Clin Neuropharmacol 27:157–162. https://doi.org/10.1097/01.wnf.0000138634.34498.05

    Article  PubMed  Google Scholar 

  52. Singh M, Meyer EM, Simpkins JW (1995) The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague-Dawley rats. Endocrinology 136:2320–2324. https://doi.org/10.1210/endo.136.5.7720680

    Article  CAS  PubMed  Google Scholar 

  53. Castrén E, Monteggia LM (2021) Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biol Psychiatry 90:128–136. https://doi.org/10.1016/j.biopsych.2021.05.008

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Nos. JP25870256 [Grant-in-Aid for Young Scientists (B) to M.F.], 16K12894 (Grant-in-Aid for Challenging Exploratory Research to M.F.), 16H05275 [Grant-in-Aid for Scientific Research (B) to M.F.], and 22K11859 [Grant-in-Aid for Scientific Research (C) to M.F.], the Takeda Science Foundation (to M.F.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to M.F.), a grant-in-aid for the Cooperative Research Project from the Institute of Natural Medicine at the University of Toyama in 2015 and 2016 (to M.F.), and the Discretionary Funds of the President of the University of Toyama [Project leader: Prof. Chihiro Tohda (Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama)]. We thank the Institute of Natural Medicine, University of Toyama for donating a library of Kampo extracts. We also appreciate the contribution of members of Prof. Shibahara’s laboratory (Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama) to the preparation of extracts. This work was performed using the Traditional Medical & Pharmaceutical Database, Institute of Natural Medicine, University of Toyama (https://dentomed.toyama-wakan.net/index/en). We thank Barry Patel, PhD, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript.

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Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan

    Hironori Nakayama, Daisuke Ihara, Mamoru Fukuchi, Chisato Yuri, Masaaki Tsuda & Akiko Tabuchi

  2. Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma, 370-0033, Japan

    Mamoru Fukuchi

  3. Department of Medicinal Resources Management, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Kazufumi Toume

  4. Kampo Education and Training Center, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Naotoshi Shibahara

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Nakayama, H., Ihara, D., Fukuchi, M. et al. The extract based on the Kampo formula daikenchuto (Da Jian Zhong Tang) induces Bdnf expression and has neurotrophic effects in cultured cortical neurons. J Nat Med 77, 584–595 (2023). https://doi.org/10.1007/s11418-023-01703-z

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