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Accelerative effects of carbazole-type alkaloids from Murraya koenigii on neurite outgrowth and their derivative’s in vivo study for spatial memory

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Abstract

Murraya koenigii is a medicinal plant that contains several carbazole-type alkaloids as its characteristic constituents. Blood–brain barrier permeable constituents of M. koenigii accelerated neurite outgrowth in PC-12 cells. Nine compounds were isolated from M. koenigii and their effects on neurite outgrowth were examined. Murrayamine-E (8) at 10 μM showed significant effect. Focusing on the carbazole skeleton, we synthesized derivatives to attenuate cytotoxicity. 9-Benzyl-9H-carbazol-4-ol (15) exhibited strong neurite outgrowth accelerative effect. In addition, the novel object recognition test and the Morris water maze test were performed to evaluate memory improvement of 15 in APdE9 mice. Compound 15 tended to improve spatial memory in the Morris water maze test. These results suggest that carbazole derivative 15 would be a seed compound for Alzheimer’s disease drug.

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References

  1. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317

    Article  CAS  Google Scholar 

  2. Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N, Ávila J, Llorens-Martín M (2019) Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med 25:554–560

    Article  CAS  Google Scholar 

  3. Winner B, Winkler J (2015) Adult neurogenesis in neurodegenerative diseases. Cold Spring Harb Perspect Biol 7:a021287

    Article  CAS  Google Scholar 

  4. Yano M, Nakashima S, Oda Y, Nakamura S, Matsuda H (2020) BBB-permeable aporphine-type alkaloids in Nelumbo nucifera flowers with accelerative effects on neurite outgrowth in PC-12 cells. J Nat Med 74:212–218

    Article  Google Scholar 

  5. Utaipan T, Athipornchai A, Suksamrarn A, Jirachotikoon C, Yuan X, Lertcanawanichakul M, Chunglok W (2017) Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells. J Nat Med 71:158–169

    Article  CAS  Google Scholar 

  6. Nalli Y, Khajuria V, Gupta S, Arora P, Riyaz-Ul-Hassan S, Ahmed Z, Ali A (2016) Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities. Org Biomol Chem 14:3322–3332

    Article  CAS  Google Scholar 

  7. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F (2018) Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 14:450–464

    Article  CAS  Google Scholar 

  8. Bachurin SO, Shevtsova EF, Makhaeva GF, Grigoriev VV, Boltneva NP, Kovaleva NV, Lushchekina SV, Shevtsov PN, Neganova ME, Redkozubova OM, Bovina EV, Gabrelyan AV, Fisenko VP, Sokolov VB, Aksinenko AY, Echeverria V, Barreto GE, Aliev G (2017) Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment. Sci Rep 7:45627

    Article  CAS  Google Scholar 

  9. Huang JY, Ma YZ, Yuan YH, Zuo W, Chu SF, Liu H, Du GH, Zhang DM, Chen NH (2016) Claulansine F promoted the neuronal differentiation of neural stem and progenitor cells through Akt/GSK-3β/β-catenin pathway. Eur J Pharmacol 786:72–84

    Article  CAS  Google Scholar 

  10. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, Becker GL, Huntington P, Goldman SE, Shen CH, Capota M, Britt JK, Kotti T, Ure K, Brat DJ, Williams NS, MacMillan KS, Naidoo J, Melito L, Hsieh J, De Brabander J, Ready JM, McKnight SL (2010) Discovery of a proneurogenic, neuroprotective chemical. Cell 142:39–51

    Article  CAS  Google Scholar 

  11. Furukawa Y, Sawamoto A, Yamaoka M, Nakaya M, Hieda Y, Choshi T, Hatae N, Okuyama S, Nakajima M, Hibino S (2019) Effects of carbazole derivatives on neurite outgrowth and hydrogen peroxide-induced cytotoxicity in Neuro2a Cells. Molecules 24:1366

    Article  CAS  Google Scholar 

  12. Rao LJM, Ramalakshmi K, Borse BB, Raghavan B (2007) Antioxidant and radical-scavenging carbazole alkaloids from the oleoresin of curry leaf (Murraya koenigii Spreng.). Food Chem 100:742–747

    Article  CAS  Google Scholar 

  13. Rahman MM, Gray AI (2005) A benzoisofuranone derivative and carbazole alkaloids from Murraya koenigii and their antimicrobial activity. Phytochem 66:1601–1606

    Article  CAS  Google Scholar 

  14. Russel RS, Muraleedharan NG, Gale SM, David DWL, John NL (1999) Biologically active carbazole alkaloids from Murraya koenigii. J Agric Food Chem 47:444–447

    Article  Google Scholar 

  15. Ma QG, Wang YG, Liu WM, Wei RR, Yang JB, Wang AG, Ji TF, Tian J, Su YL (2014) Hepatoprotective sesquiterpenes and rutinosides from Murraya koenigii (L.) Spreng. J Agric Food Chem 7:4145–4151

    Article  CAS  Google Scholar 

  16. Nakamura S, Nakashima S, Oda Y, Yokota N, Fujimoto K, Matsumoto T, Ohta T, Ogawa K, Maeda S, Nishida S, Matsuda H, Yoshikawa M (2013) Alkaloids from Sri Lankan curry-leaf (Murraya koenigii) display melanogenesis inhibitory activity: structures of karapinchamines A and B. Bioorg Med Chem 21:1043–1049

    Article  CAS  Google Scholar 

  17. Kitawaki T, Hayashi Y, Ueno A, Chida N (2006) One-step construction of carbazoles by way of the palladium-catalyzed double N-arylation reaction and its application to the total synthesis of murrastifoline-A. Tetrahedron 62:6792–6801

    Article  CAS  Google Scholar 

  18. Sissouma D, Maingot L, Collet S, Guingant A (2006) Concise and efficient synthesis of calothrixin B. J Org Chem 71:8384–8389

    Article  CAS  Google Scholar 

  19. Oda Y, Nakashima S, Nakamura S, Yano M, Akiyama M, Imai K, Kimura T, Nakata A, Tani M, Matsuda H (2016) New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition. J Nat Med 70:384–390

    Article  CAS  Google Scholar 

  20. Bai D, Jin G, Zhang D, Zhao L, Wang M, Zhu Q, Zhu L, Sun Y, Liu X, Chen X, Zhang L, Li W, Cui Y (2019) Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice. J Physiol Sci 69:643–652

    Article  CAS  Google Scholar 

  21. Takata K, Amamiya T, Mizoguchi H, Kawanishi S, Kuroda E, Kitamura R, Ito A, Saito Y, Tawa M, Nagasawa T, Okamoto H, Sugino Y, Takegami S, Kitade T, Toda Y, Kem WR, Kitamura Y, Shimohama S, Ashihara E (2018) Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates Aβ accumulation through suppression of neuronal γ-secretase activity and promotion of microglial amyloid-β phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer’s disease. Neurobiol Aging 62:197–209

    Article  CAS  Google Scholar 

  22. Miura H, Takano K, Kitao Y, Hibino S, Choshi T, Murakami R, Suzuki H, Yamada M, Ogawa S, Hori O (2008) A carbazole derivative protects cells against endoplasmic reticulum (ER) stress and glutathione depletion. J Pharmacol Sci 108:164–171

    Article  CAS  Google Scholar 

  23. Kollmer M, Close W, Funk L, Rasmussen J, Bsoul A, Schierhorn A, Schmidt M, Sigurdson CJ, Jucker M, Fändrich M (2019) Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue. Nat Comm 10:4760

    Article  CAS  Google Scholar 

  24. Salado IG, Zaldivar-Diez J, Sebastián-Pérez V, Li L, Geiger L, González S, Campillo NE, Gil C, Morales AV, Perez DI, Martinez A (2017) Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold: potential pro-neurogenic agents. Eur J Med Chem 138:328–342

    Article  CAS  Google Scholar 

  25. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17:157–165

    Article  CAS  Google Scholar 

  26. Gong Y, Chen J, Jin Y, Wang C, Zheng M, He L (2020) GW9508 ameliorates cognitive impairment via the cAMP-CREB and JNK pathways in APPswe/PS1dE9 mouse model of Alzheimer’s disease. Neuropharmacology 164:107899

    Article  CAS  Google Scholar 

  27. Myskiw JC, Rossato JI, Bevilaqua LRM, Medina JH, Izquierdo I, Cammarota M (2008) On the participation of mTOR in recognition memory. Neurobiol Learn Mem 89:338–351

    Article  CAS  Google Scholar 

  28. Nagakura A, Shitaka Y, Yarimizu J, Matsuoka N (2013) Characterization of cognitive deficits in a transgenic mouse model of Alzheimer’s disease and effects of donepezil and memantine. Eur J Pharmacol 703:53–61

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacognosy, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan

    Mamiko Yano, Souichi Nakashima, Shiori Kasa, Seikou Nakamura, Yoshimi Oda & Hisashi Matsuda

  2. Division of Integrated Pharmaceutical Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan

    Kaneyasu Nishimura & Kazuyuki Takata

  3. N.T.H Co., Ltd., 1-8-11 4F Sky-ebisu Bldg., Ebisu, Shibuya-ku, Tokyo, 150-0013, Japan

    Yoshimi Oda

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  1. Mamiko Yano
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  2. Souichi Nakashima
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Correspondence to Hisashi Matsuda.

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Yano, M., Nakashima, S., Kasa, S. et al. Accelerative effects of carbazole-type alkaloids from Murraya koenigii on neurite outgrowth and their derivative’s in vivo study for spatial memory. J Nat Med 74, 448–455 (2020). https://doi.org/10.1007/s11418-020-01388-8

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  • DOI: https://doi.org/10.1007/s11418-020-01388-8

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