Korean Journal of Agricultural Science (농업과학연구)

Institute of Agricultural Science, CNU (충남대학교 농업과학연구소)
권호 표지
DOI QR코드

DOI QR Code

Protective effects of Cirsium japonicum var. maackii against amyloid beta-induced neurotoxicity in C6 glial cells

  • Kim, Ji Hyun (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Kim, Min Jeong (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Choi, Ji Myung (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University) ;
  • Lee, Sanghyun (Department of Plant Science and Technology, Chung-Ang University) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University)
  • Received : 2019.05.05
  • Accepted : 2019.05.28
  • Published : 2019.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with age, and amyloid beta ($A{\beta}$) is known to cause Alzheimer's disease. In the present study, we investigated the protective effects of Cirsium japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells. The cells treated with $A{\beta}_{25-35}$ showed a decrease in cell viability and an increase in reactive oxygen species (ROS) production compared with the non-treated cells. However, the cells treated with the C. japonicum var. maackii extract and its fractions increased the cell viability and inhibited the $A{\beta}$-induced ROS production. These results demonstrate the neuroprotective effects of C. japonicum var. maackii against $A{\beta}$. To further examine the protective mechanism, we measured inflammation and apoptosis related protein expressions. The cells treated with extract and fractions from C. japonicum var. maackii down-regulated inflammatory related proteins such as cyclooxygenase-2, interleukin $(IL)-1{\beta}$, and IL-6, and attenuated apoptosis related proteins including B-cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio. In particular, the ethanol and ethylacetate fraction exhibited higher inhibitory effect against ROS production and apoptosis-related protein expressions among the extract and the other fractions. Therefore, this study demonstrated the protective effects of C. japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells through the regulation of oxidative stress, inflammation, and apoptosis, suggesting that it might have potential as a therapeutic for AD.

Keywords

CNNSA3_2019_v46n2_369_f0001.png 이미지

Fig. 1. Effect of Cirsium japonicum var. maackii extract (ext.) and fractions (fr.) on cell viability in Aβ25-35-treated C6 glial cells. Values are means ± SD (n = 3). a - c: Means with the different letters are significantly different (p < 0.05) by Duncan's multiple range test among extract- and fractions-treated groups. *p < 0.05 compared with the control group by Student’s t-test.

CNNSA3_2019_v46n2_369_f0002.png 이미지

Fig. 2. Effect of Cirsium japonicum var. maackii extract (ext.) and fractions (fr.) on reactive oxygen species (ROS) production in Aβ25-35-treated C6 glial cells. Time course of change in intensity of ROS fluorescence during 1 h (A) and production of ROS at 1 h (B). Values are means ± SD (n = 3). NS, non-significance. a, b: Means with the different letters are significantly different (p < 0.05) by Duncan's multiple range test among extract- and fractions-treated groups. *p < 0.05 compared with the control group by Student's t-test.

CNNSA3_2019_v46n2_369_f0003.png 이미지

Fig. 3. Effect of Cirsium japonicum var. maackii extract (ext.) and fractions (fr.) on inflammation-related protein expressions in Aβ25-35-treated C6 glial cells. Protein bands intensity of COX-2, IL-1β, and IL-6 (A) and quantitative analysis of COX-2 (B), IL-1β (C), and IL-6 (D). Values are means ± SD (n = 3). a - g: Means with the different letters are significantly different (p < 0.05) by Duncan's multiple range test.

CNNSA3_2019_v46n2_369_f0004.png 이미지

Fig. 4. Effect of Cirsium japonicum var. maackii extract (ext.) and fractions (fr.) on apoptosis-related protein expressions in Aβ25-35-treated C6 glial cells. Values are means ± SD (n = 3). a - g: Means with the different letters are significantly different (p < 0.05) by Duncan's multiple range test.

References

  1. Ali T, Kim MJ, Rehman SU, Ahmad A, Kim MO. 2017. Anthocyanin-loaded PEG-gold nanoparticles enhanced the neuroprotection of anthocyanins in an $A{\beta}1$-42 mouse model of Alzheimer's disease. Molecular Neurobiology 54:6490-6506. https://doi.org/10.1007/s12035-016-0136-4
  2. Apelt J, Schliebs R. 2001. Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Research 894:21-30. https://doi.org/10.1016/S0006-8993(00)03176-0
  3. Block ML, Hong JS. 2005. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Progress Neurobiology 76:77-98. https://doi.org/10.1016/j.pneurobio.2005.06.004
  4. Butterfield DA, Swomley AM, Sultana R. 2013. Amyloid $\beta$-peptide (1-42)-induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression. Antioxidants & Redox Signaling 19:823-835. https://doi.org/10.1089/ars.2012.5027
  5. Canevari L, Abramov AY, Duchen MR. 2004. Toxicity of amyloid beta peptide: Tales of calcium, mitochondria, and oxidative stress. Neurochemical Research 29:637-650. https://doi.org/10.1023/B:NERE.0000014834.06405.af
  6. 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 Biology 14:450-464. https://doi.org/10.1016/j.redox.2017.10.014
  7. Cheng HY, Hsieh MT, Tsai FS, Wu CR, Chiu CS, Lee MM, Xu HX, Zhao ZZ, Peng WH. 2010. Neuroprotective effect of luteolin on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons. Phytotherapy Research 24:102-108. https://doi.org/10.1002/ptr.2940
  8. Fang F, Liu GT. 2006. Protective effects of compound FLZ on beta-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment. Acta Pharmacol ogica Sinica 27:651-658. https://doi.org/10.1111/j.1745-7254.2006.00347.x
  9. Farfara D, Lifshitz V, Frenkel D. 2008. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. Journal of Cellular and Molecular Medicine 12:762-780. https://doi.org/10.1111/j.1582-4934.2008.00314.x
  10. Ferreiro E, Eufrasio A, Pereira C, Oliveira CR, Rego AC. 2007. Bcl-2 overexpression protects against amyloid-beta and prion toxicity in GT1-7 neural cells. Journal of Alzheimer's Disease 12:223-228. https://doi.org/10.3233/JAD-2007-12303
  11. Halliday G, Robinson SR, Shepherd C, Kril J. 2000. Alzheimer's disease and inflammation: A review of cellular and therapeutic mechanisms. Clinical and Experimental Pharmacology and Physiology 27:1-8. https://doi.org/10.1046/j.1440-1681.2000.03200.x
  12. Han JY, Ahn SY, Kim CS, Yoo SK, Kim SK, Kim HC, Hong JT, Oh KW. 2012. Protection of apigenin against kainate-induced excitotoxicity by anti-oxidative effects. Biological and Pharmaceutical Bulletin 35:1440-1446. https://doi.org/10.1248/bpb.b110686
  13. Han XJ, Hu YY, Yang ZJ, Jiang LP, Shi SL, Li YR, Guo MY, Wu HL, Wan YY. 2017. Amyloid $\beta$-42 induces neuronal apoptosis by targeting mitochondria. Molecular Medicine Reports 16:4521-4528. https://doi.org/10.3892/mmr.2017.7203
  14. Huang L, Huang K, Ning H. 2018. Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats. Biomedicine & Pharmacotherapy 97:412-422. https://doi.org/10.1016/j.biopha.2017.10.142
  15. Jung HA, Kim YS, Choi JS. 2009. Quantitative HPLC analysis of two key flavonoids and inhibitory activities against aldose reductase from different parts of the Korean thistle, Cirsium maackii. Food Chemical Toxicology 47:2790-2797. https://doi.org/10.1016/j.fct.2009.08.014
  16. Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, Zaheer S, Iyer SS, Zaheer A. 2016. Neuroinflammation induces neurodegeneration. Journal of Neurology Neurosurgery and Spine 1:1003.
  17. Kim SJ, Kim GH. 2003. Identification for flavones in different parts of Cirsium japonicum. Journal of Food Science and Nutrition 8:330-353.
  18. Kim JH, Wang Q, Choi JM, Lee S, Cho EJ. 2015. Protective role of caffeic acid in an $A{\beta}$ 25-35-induced Alzheimer's disease model. Nutrition Research and Practice 9:480-488. https://doi.org/10.4162/nrp.2015.9.5.480
  19. Kitamura Y, Shimohama S, Kamoshima W, Ota T, Matsuoka Y, Nomura Y, Smith MA, Perry G, Whitehouse PJ, Taniguchi T. 1998. Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease. Brain Research 780:260-269. https://doi.org/10.1016/S0006-8993(97)01202-X
  20. Lau TL, Gehman JD, Wade JD, Perez K, Masters CL, Barnham KJ, Separovic F. 2007. Membrane interactions and the effect of metal ions of the amyloidogenic fragment Abeta (25-35) in comparison to Abeta (1-42). Biochimica et Biophysica Acta 1768:2400-2408. https://doi.org/10.1016/j.bbamem.2007.05.004
  21. Lee AY, Kim MJ, Lee S, Cho EJ. 2018. Protective effect of Cirsium japonicum var. maackii against oxidative stress in C6 glial cells. Korean Journal of Agricultural Science 45:509-519. [in Korean] https://doi.org/10.7744/kjoas.20180031
  22. Lee J, Rodriguez JP, Lee KH, Park JY, Kang KS, Hahm DH, Huh CK, Lee SC, Lee S. 2017. Determination of flavonoids from Cirsium japonicum var. maackii and their inhibitory activities against aldose reductase. Applied Biological Chemistry 60:487-496. https://doi.org/10.1007/s13765-017-0302-z
  23. Liao Z, Chen X, Wu M. 2010. Antidiabetic effect of flavones from Cirsium japonicum DC in diabetic rats. Archives Pharmacal Research 33:353-362. https://doi.org/10.1007/s12272-010-0302-6
  24. Liu Y, Tian X, Gou L, Sun L, Ling X, Yin X. 2013. Luteolin attenuates diabetes-associated cognitive decline in rats. Brain Research Bulletin 94:23-29. https://doi.org/10.1016/j.brainresbull.2013.02.001
  25. Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima T. 2009. Silibinin attenuates amyloid beta (25-35) peptide-induced memory impairments: Implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. Journal of Pharmacology and Experimental Therapeutics 331:319-326. https://doi.org/10.1124/jpet.109.155069
  26. Ma Y, Ma B, Shang Y, Yin Q, Hong Y, Xu S, Shen C, Hou X, Liu X. 2018. Flavonoid-rich ethanol extract from the leaves of Diospyros kaki attenuates cognitive deficits, amyloid-beta production, oxidative stress, and neuroinflammation in APP/PS1 transgenic mice. Brain Research 1678:85-93. https://doi.org/10.1016/j.brainres.2017.10.001
  27. Mattson MP, Begley JG, Mark RJ, Furukawa K. 1997. Abeta25-35 induces rapid lysis of red blood cells: Contrast with Abeta1-42 and examination of underlying mechanisms. Brain Research 771:147-153. https://doi.org/10.1016/S0006-8993(97)00824-X
  28. Mok JY, Kang HJ, Cho JK, Jeon IH, Kim HS, Park JM, Jeong SI, Shim JS, Jang SI. 2011. Antioxidative and anti-inflammatory effects of extracts from different organs of cirsium japonicum var. ussuriense. The Korea Journal of Herbology 26:39-47. [in Korean]
  29. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65:55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  30. Obulesu M, Lakshmi MJ. 2014. Apoptosis in Alzheimer's disease: An understanding of the physiology, pathology and therapeutic avenues. Neurochemical Research 39:2301-2312. https://doi.org/10.1007/s11064-014-1454-4
  31. Price JL, Morris JC. 1999. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Annals of Neurology 45:358-368. https://doi.org/10.1002/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X
  32. Rastogi RP, Singh SP, Hader DP, Sinha RP. 2010. Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochemical Biophysical Research Communications 397:603-607. https://doi.org/10.1016/j.bbrc.2010.06.006
  33. Sawikr Y, Yarla NS, Peluso I, Kamal MA, Aliev G, Bishayee A. 2017. Neuroinflammation in Alzheimer's disease: The preventive and therapeutic potential of polyphenolic nutraceuticals. Advances Protein Chemistry Structural Biology 108:33-57. https://doi.org/10.1016/bs.apcsb.2017.02.001
  34. Shin MS, Park JY, Lee J, Yoo HH, Hahm DH, Lee SC, Lee S, Hwang GS, Jung K, Kang KS. 2017. Anti-inflammatory effects and corresponding mechanisms of cirsimaritin extracted from Cirsium japonicum var. maackii Maxim. Bioorganic & Medicinal Chemistry Letters 27:3076-3080. https://doi.org/10.1016/j.bmcl.2017.05.051
  35. Tanaka J, Toku K, Zhang B, Ishihara K, Sakanaka M, Maeda N. 1999. Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species. Glia 28:85-96. https://doi.org/10.1002/(SICI)1098-1136(199911)28:2<85::AID-GLIA1>3.0.CO;2-Y
  36. Travis J. 1994. Glia: The brain's other cells. Science 266:970-972. https://doi.org/10.1126/science.7973679
  37. Wan Y, Liu LY, Hong ZF, Peng J. 2014. Ethanol extract of Cirsium japonicum attenuates hepatic lipid accumulation via AMPK activation in human HepG2 cells. Experimental and Therapeutic Medicine 8:79-84. https://doi.org/10.3892/etm.2014.1698
  38. Wang H, Joseph JA. 1999. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radical Biology & Medicine 27:612-616. https://doi.org/10.1016/S0891-5849(99)00107-0
  39. Yang DI, Yeh CH, Chen S, Xu J, Hsu CY. 2004. Neutral sphingomyelinase activation in endothelial and glial cell death induced by amyloid beta-peptide. Neurobiology of Disease 17:99-107. https://doi.org/10.1016/j.nbd.2004.06.001
  40. Yu TX, Zhang P, Guan Y, Wang M, Zhen MQ. 2015. Protective effects of luteolin against cognitive impairment induced by infusion of $A{\beta}$ peptide in rats. International Journal of Clinical Experimental Pathology 8:6740-6747.

Cited by

  1. Neuroprotective Effect of ent -Kaur-15-en-17-al-18-oic Acid on Amyloid Beta Peptide-Induced Oxidative Apoptosis in Alzheimer’s Disease vol.25, pp.1, 2019, https://doi.org/10.3390/molecules25010142
  2. Effect of Donganme (Sorghum bicolor L. Moench) against oxidative stress in vitro and in a cellular system in glial cells vol.47, pp.3, 2020, https://doi.org/10.7744/kjoas.20200039
  3. Amelioration effects ofCirsium japonicumvar.maackiiextract/fractions on amyloid beta25-35-induced neurotoxicity in SH-SY5Y cells and identification of the main bioactive compound vol.11, pp.11, 2020, https://doi.org/10.1039/d0fo01041c