DOI QR코드

DOI QR Code

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models

  • Huh, Eugene (College of Korean Medicine, Kyung Hee University) ;
  • Kim, Hyo Geun (College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University) ;
  • Park, Hanbyeol (Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University) ;
  • Kang, Min Seo (College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University) ;
  • Lee, Bongyong (College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University) ;
  • Oh, Myung Sook (College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University)
  • Received : 2014.04.01
  • Accepted : 2014.04.15
  • Published : 2014.05.31

Abstract

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Keywords

References

  1. Ansari, M. A, Abdul, H. M., Joshi, G., Opii, W. O. and Butterfield, D. A. (2009) Protective effect of quercetin in primary neurons against A$\beta$(1-42): relevance to Alzheimer's disease. J. Nutr. Biochem. 20, 269-275. https://doi.org/10.1016/j.jnutbio.2008.03.002
  2. Arora, K., Alfulaij, N., Higa, J. K., Panee, J. and Nichols, R. A. (2013) Impact of sustained exposure to $\beta$-amyloid on calcium homeostasis and neuronal integrity in model nerve cell system expressing $\alpha$4$\beta$2 nicotinic acetylcholine receptors. J. Biol. Chem. 288, 11175-11190. https://doi.org/10.1074/jbc.M113.453746
  3. Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B. A. (1995) Betaamyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 14, 879-888. https://doi.org/10.1016/0896-6273(95)90232-5
  4. Chen, Y. Y., Liu, J. F., Chen, C. M., Chao, P. Y. and Chang, T. J. (2003) A study of the antioxidative and antimutagenic effects of Houttuynia cordata Thunb. using an oxidized frying oil-fed model. J. Nutr. Sci. Vitaminol. 49, 327-333. https://doi.org/10.3177/jnsv.49.327
  5. Collombet, J. M., Beracochea, D., Liscia, P., Pierard, C., Lallement, G. and Filliat, P. (2011) Long-term effects of cytokine treatment on cognitive behavioral recovery and neuronal regeneration in somanpoisoned mice. Behav. Brain Res. 221, 261-270. https://doi.org/10.1016/j.bbr.2011.03.006
  6. Conrad, C. D., Galea, L. A., Kuroda, Y. and McEwen, B. S. (1996) Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav. Neurosci. 110, 1321-1334. https://doi.org/10.1037/0735-7044.110.6.1321
  7. Das, A., Shanker, G., Nath, C., Pal, R., Singh, S. and Singh, H. K. (2002) A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol. Biochem. Behav. 73, 893-900. https://doi.org/10.1016/S0091-3057(02)00940-1
  8. Drachman, D. A. and Leavitt, J. (1974) Human memory and the cholinergic system. A relationship to againg? Arch. Neurol. 30, 113-121. https://doi.org/10.1001/archneur.1974.00490320001001
  9. Duan, D. X., Chai, G. S., Ni, Z. F., Hu, Y., Luo, Y., Cheng, X. S., Chen, N. N., Wang, J. Z. and Liu, G. P. (2013) Phosphorylation of tau by death-associated protein kinase 1 antagonizes the kinase-induced cell apoptosis. J. Alzheimers. Dis. 37, 795-808.
  10. Ellman, G. L., Courtney, K. D., Andres, V. Jr. and Feather-stone, R. M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  11. Farlow, M. R. and Cummings, J. (2008) A modern hypothesis: the distinct pathologies of dementia associated with Parkinson's disease versus Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 25, 301-308. https://doi.org/10.1159/000119104
  12. Grace, E. A., Rabiner, C. A. and Busciglio, J. (2002) Characterization of neuronal dystrophy induced by fibrillar amyloidb: implications for Alzheimer's disease. Neuroscience 114, 265-273. https://doi.org/10.1016/S0306-4522(02)00241-5
  13. Grayson, B., Idris, N. F. and Neill, J. C. (2007) Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat. Behav. Brain Res. 184, 31-38. https://doi.org/10.1016/j.bbr.2007.06.012
  14. Hartig, W., Stieler, J., Boerema, A. S., Wolf, J., Schmidt, U., Weissfuss, J., Bullmann, T., Strijkstra, A. M. and Arendt, T. (2007) Hibernation model of tau phosphorylation in hamsters: selective vulnerability of cholinergic basal forebrain neurons - implications for Alzheimer's disease. Eur. J. Neurosci. 25, 69-80. https://doi.org/10.1111/j.1460-9568.2006.05250.x
  15. Huang, S. M., Chuang, H. C., Wu, C. H. and Yen, G. C. (2008) Cytoprotective effects of phenolic acids on methylglyoxal-induced apoptosis in Neuro-2A cells. Mol. Nutr. Food Res. 52, 940-949. https://doi.org/10.1002/mnfr.200700360
  16. Jayapalan, S. and Natarajan, J. (2013) The role of CDK5 and GSK3B kinases in hyperphosphorylation of microtubule associated protein tau (MAPT) in Alzheimer's disease. Bioinformation 9, 1023-1030. https://doi.org/10.6026/97320630091023
  17. Joseph, J. A., Shukitt-Hale, B., Brewer, G. J., Weikel, K. A., Kalt, W. and Fisher, D. R. (2010) Differential protection among fractionated blueberry polyphenolic families against DA-, Ab(42)- and LPSinduced decrements in Ca(2+) buffering in primary hippocampal cells. J. Agric. Food Chem. 58, 8196-8204. https://doi.org/10.1021/jf100144y
  18. Karasawa, J., Hashimoto, K. and Chaki, S. (2008) D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats. Behav. Brain Res. 186, 78-83. https://doi.org/10.1016/j.bbr.2007.07.033
  19. Khan, M. M., Ahmad, A., Ishrat, T., Khuwaja, G., Srivastawa, P., Khan, M. B., Raza, S. S., Javed, H., Vaibhav, K., Khan, A. and Islam, F. (2009) Rutin protects the neural damage induced by transient focal ischemia in rats. Brain Res. 1292, 123-135. https://doi.org/10.1016/j.brainres.2009.07.026
  20. Kim, H. G., Moon, M., Choi, J. G., Park, G., Kim A. J., Hur, J., Lee, K. T. and Oh, M. S. (2014) Donepezil inhibits the amyloid-beta oligomer- induced microglial activation in vitro and in vivo. Neurotoxicology 40, 23-32. https://doi.org/10.1016/j.neuro.2013.10.004
  21. Kwon, S. H., Lee, H. K., Kim, J. A., Hong, S. I., Kim, H. C., Jo, T. H., Park, Y. I., Lee, C. K., Kim, Y. B., Lee, S. Y. and Jang, C. G. (2010) Neuroprotective effects of chlorogenic acid on scopolamineinduced amnesia via anti-acetylcholiesterase and anti-oxidative activities in mice. Eur. J. Pharmacol. 649, 210-217. https://doi.org/10.1016/j.ejphar.2010.09.001
  22. Leon, R. and Marco-Contelles, J. (2011) A step further towards multitarget drugs for Alzheimer and neuronal vascular diseases: targeting the cholinergic system, amyloid-$\beta$ aggregation and Ca(2+) dyshomeostasis. Curr. Med. Chem. 18, 552-576. https://doi.org/10.2174/092986711794480186
  23. Lee, M., Kwon, Y. T., Li, M., Peng, J., Friedlander, R. M. and Tsai, L. H. (2000) Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405, 360-364. https://doi.org/10.1038/35012636
  24. Mondragon-Rodriguez, S., Perry, G., Luna-Munoz, J., Acevedo-Aquino, M. C. and Williams, S. (2014) Phosphorylation of tau protein at sites Ser (396-404) is one of the earliest events in Alzheimer's disease and Down syndrome. Neuropathol. Appl. Neurobiol. 40, 121-135. https://doi.org/10.1111/nan.12084
  25. Nuengchamnong, N., Krittasilp, K. and Ingkaninan, K. (2009) Rapid screening and identification of antioxidants in aqueous extracts of Houttuynia cordata using LC-ESI-MS coupled with DPPH assay. Food Chem. 117, 750-756. https://doi.org/10.1016/j.foodchem.2009.04.071
  26. Oh, S. R., Kim, S. J., Kim, D. H., Ryu, J. H., Ahn, E. M. and Jung, J. W. (2013) Angelica keiskei ameliorates scopolamine-induced memory impairments in mice. Biol. Pharm. Bull. 36, 82-88.
  27. Park, H. and Oh, M. S. (2012) Houttuyniae Herba protects rat primary cortical cells from A$\beta$(25-35)-induced neurotoxicity via regulation of calcium influx and mitochondria-mediated apoptosis. Hum. Exp. Toxicol. 31, 698-709. https://doi.org/10.1177/0960327111433898
  28. Paxinos, G. and Franklin, K. B. J. (2001) The mouse brain in stereotaxic coordinates. 2nd ed. San Diego: Academic Press.
  29. Roozendaal, B. (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiol. Learn. Mem. 78, 578-595. https://doi.org/10.1006/nlme.2002.4080
  30. Schliebs, R. and Arendt, T. (2011) The cholinergic system in aging and neuronal degeneration. Behav. Brain Res. 221, 555-563. https://doi.org/10.1016/j.bbr.2010.11.058
  31. Shi, L., Dong, R. and Ji, J. (2004) Effect of Herba Houttuyniae injection on the ability of learning and memory of mice. J. Southeast University.
  32. Shin, S., Joo, S. S., Jeon, J. H., Park, D., Jang, M. J., Kim, T. O., Kim, H. K., Hwang, B. Y., Kim, K. Y. and Kim, Y. B. (2010) Antiinflammatory effects of a Houttuynia cordata supercritical extract. J. Vet. Sci. 11, 273-275. https://doi.org/10.4142/jvs.2010.11.3.273
  33. Shors, T. J., Miesegaes, G., Beylin, A., Zhao, M., Rydel, T. and Gould, E. (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372-376. https://doi.org/10.1038/35066584
  34. Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A. and Katzman, R. (1991) Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572-580. https://doi.org/10.1002/ana.410300410
  35. Tian, L., Zhao, Y., Guo, C. and Yang, X. (2011) A comparative study on the antioxidant activities of an acidic polysaccharide and various solvent extracts derived from herbal Houttuynia cordata. Carbohydr. Polym. 83, 537-544. https://doi.org/10.1016/j.carbpol.2010.08.023
  36. Toda, S. (2005) Antioxidative effects of polyphenols in leaves of Houttuynia cordata on protein fragmentation by copper-hydrogen peroxide in vitro. J. Med. Food 8, 266-268. https://doi.org/10.1089/jmf.2005.8.266
  37. Van der Zee, E. A. and Luiten, P. G. (1999) Muscarinic acetylcholine receptors in the hippocampus, neocortex and amygdala: a review of immunocytochemical localization in relation to learning and memory. Prog. Neurobiol. 58, 409-471. https://doi.org/10.1016/S0301-0082(98)00092-6
  38. Zhang, L., Zhang, W. P., Chen, K. D., Qian, X. D., Fang, S. H., Wei, E. Q. (2007) Caffeic acid attenuates neuronal damage, astrogliosis and glial scar formation in mouse brain with cryoinjury. Life Sci. 80, 530-537. https://doi.org/10.1016/j.lfs.2006.09.039
  39. Zhao, B. (2009) Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease. Neurochem. Res. 34, 630-638. https://doi.org/10.1007/s11064-008-9900-9
  40. Zheng, W. H., Bastianetto, S., Mennicken, F., Ma, W. and Kar, S. (2002) Amyloid $\beta$ peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. Neuroscience 115, 201-211. https://doi.org/10.1016/S0306-4522(02)00404-9
  41. Zussy, C., Brureau, A., Delair, B., Marchal, S., Keller, E., Ixart, G., Naert, G., Meunier, J., Chevallier, N., Maurice, T., Givalois L. (2011) Time-course and regional analyses of the physiopathological changes induced after cerebral injection of an amyloid $\beta$ fragment in rats. Am. J. Pathol. 179, 315-334. https://doi.org/10.1016/j.ajpath.2011.03.021

Cited by

  1. Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer’s disease vol.36, pp.11, 2015, https://doi.org/10.1007/s10072-015-2314-y
  2. Determination of dibutyl phthalate neurobehavioral toxicity in mice vol.94, 2016, https://doi.org/10.1016/j.fct.2016.05.006
  3. Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo vol.171, 2015, https://doi.org/10.1016/j.jep.2015.05.054
  4. Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus vol.791, 2016, https://doi.org/10.1016/j.ejphar.2016.08.003
  5. White Ginseng Protects Mouse Hippocampal Cells Against Amyloid-Beta Oligomer Toxicity vol.31, pp.3, 2017, https://doi.org/10.1002/ptr.5776
  6. Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling vol.30, pp.2, 2016, https://doi.org/10.1002/ptr.5511
  7. Chemical Composition and Allelopathic, Antibacterial, Antifungal, and Antiacetylcholinesterase Activity of Fish-mint (Houttuynia cordata Thunb .) from India 2017, https://doi.org/10.1002/cbdv.201700189
  8. Modulation of LOX and COX pathways via inhibition of amyloidogenesis contributes to mitoprotection against β-amyloid oligomer-induced toxicity in an animal model of Alzheimer's disease in rats vol.146-147, 2016, https://doi.org/10.1016/j.pbb.2016.04.002
  9. plaque injected mice vol.9, pp.1, 2018, https://doi.org/10.1039/C7FO01149K
  10. Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by upregulating hippocampal estrogen synthesis vol.17, pp.None, 2014, https://doi.org/10.1186/s12906-017-2015-6
  11. 어성초(魚腥草)의 항산화 효능 확인 및 모유두 세포의 5α-reductase 유전자 발현에 미치는 영향 vol.31, pp.6, 2014, https://doi.org/10.15188/kjopp.2017.12.31.6.356
  12. Norcepharadione B attenuates H2O2-induced neuronal injury by upregulating cellular antioxidants and inhibiting volume-sensitive Cl channel vol.244, pp.16, 2014, https://doi.org/10.1177/1535370219881358
  13. Herba houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade vol.12, pp.1, 2020, https://doi.org/10.3390/nu12010164
  14. The Interplay Between Beta-Amyloid 1–42 (Aβ 1–42 )-Induced Hippocampal Inflammatory Response, p-tau, Vascular Pathology, and Their Synergistic Contributions to Neuronal D vol.13, pp.None, 2014, https://doi.org/10.3389/fnmol.2020.552073
  15. The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo vol.12, pp.5, 2014, https://doi.org/10.3390/nu12051372
  16. Sodium Houttuyfonate Ameliorates β-amyloid1-42-Induced Memory Impairment and Neuroinflammation through Inhibiting the NLRP3/GSDMD Pathway in Alzheimer’s Disease vol.2021, pp.None, 2014, https://doi.org/10.1155/2021/8817698