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파킨슨유발제인 이산화망간으로 손상된 배양 대뇌 신경아교세포에 대한 노박덩굴 추출물의 보호

Protective Effect of Celastrus orbiculatus Thunb Extract on Cultured Neuroglial Cells Damaged by Manganese Dioxide, a Parkinsonism Inducer

  • Seo, Young-Mi (Department of Nursing, Wonkwang Health Science University)
  • 투고 : 2020.04.29
  • 심사 : 2020.05.21
  • 발행 : 2020.06.30

초록

본 연구는 이산화망간(MnO2)의 신경독성과 이에 대한 노박 덩굴 추출물의 보호 효과를 C6 glioma 세포를 배양하여 조사하였다. 본 연구를 위하여 세포생존율을 비롯하여 지질산화(LP) 억제능 및 XO 저해능과 같은 항산화 분석을 시행하였다. 그 결과 MnO2는 배양 세포에 처리한 농도에 비례하여 세포생존율을 유의하게 감소시켰으며, 이 과정에서 XTT50값은 146.7 μM로 나타나 Borenfreund and Puerner의 독성판정기준에 따라 중간독성(mid-cytotoxic)인 것으로 나타났다. 또한, 항산화제의 일종인 kaempferol (KAE)은 MnO2의 독성에 의해 손상받은 세포의 생존율을 유의하게 증가시킴으로써 MnO2의 독성을 방어하였다. 한편, MnO2 독성에 대한 노박덩굴(CO) 추출물의 영향 조사에 있어서, CO 추출물은 배양 세포에 MnO2만을 처리한 것에 비하여 세포생존율을 유의하게 증가시킴으로써 MnO2의 독성을 효과적으로 방어하였다. 이와 동시에 높은 LP 억제능과 XO 저해능과 같은 항산화 효과를 보여주었다. 이상의 결과에서 MnO2의 독성에 산화적 손상이 관여하고 있음을 알 수 있었으며, CO 추출물은 LP 억제능과 XO 저해능과 같은 항산화능에 의하여 MnO2의 독성을 효과적으로 방어한 것을 확인였다. 따라서, CO 추출물과 같은 천연소재는 파킨슨병 유발제인 MnO2와 같이 산화적 손상과 관련된 질환적 중금속 독성을 경감 내지는 개선할 수 있는 유용한 물질이라 생각된다.

The protective effects of a Celastrus orbiculatus Thunb (CO) extract against manganese dioxide (MnO2)-induced cytotoxicity in cultured C6 glioma cells were examined. This study assessed the antioxidative effects, including the suppressive ability of lipid peroxidation (LP), the inhibitory ability of xanthine oxidase (XO), and the cell viability. MnO2 decreased the cell viability remarkably in a dose-dependent manner. The XTT50 value was determined to be 146.7 μM in these cultures. The cytotoxicity of MnO2 was calculated to be mid-toxic using Borenfreund and Puerner's toxic criteria. Kaempferol (KAE) increased the cell viability damaged by MnO2-induced cytotoxicity significantly. Regarding the protective effects of the CO extract on MnO2-induced cytotoxicity, the CO extract increased cell viability significantly compared to the MnO2-treated group. The CO extract also had inhibitory abilities against lipid peroxidation (LP) and xanthine oxidase (XO). From these findings, oxidative stress is involved in the cytotoxicity of MnO2. The CO extract effectively blocked the cytotoxicity induced by MnO2 via its antioxidative effects. Conclusively, natural resources, such as the CO extract, might be a useful agent for the diminution or improvement of the heavy metal cytotoxicity correlated with disease through oxidative stress, such as MnO2, a Parkinsonism inducer.

키워드

참고문헌

  1. Rosen D, Siddique T, Patterson D, Fiqlewiez D, Sapp P, Hentati A, et al. Mutation in Cu/Zn superoxidedismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59-62. https://doi.org/10.1038/362059a0
  2. Ra JS, Lee JH, Kim KT. Application of toxicity identification evaluation procedures for toxic effluents from the aluminum rolling industry. J Environ Health Sci. 2015;41:305-313. https://doi.org/10.5668/JEHS.2015.41.5.305
  3. Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003;348:1356-1364. http://dx.doi.org/10.1056/NEJM2003ra020003
  4. Jung IJ. The effect of NMDA/glycine receptor antagonist, 7-chlorokynurenic acid on cultured astrocytes damaged by ischemia- like condition. J Exp Biomed Sci. 2009;15:355-362.
  5. Cho KS. Occupational health. 2 ed. Seoul: Sumoonsa Publishing; 1991. p315-319.
  6. Choi JH, Jang BK, Lee JW, Hong EJ, Lee MJ, Ji DH. Cerebral activity by motor task in welders exposed to manganese through fMRI. J Environ Health Sci. 2011;37:102-112. http://dx.doi.org/10.5668/JEHS.2011.37.2.102
  7. Lee SH, Jung IJ, Jang HS. The antioxidative effect of Eclipta prostrata L. extract on cultured NIH3T3 fibroblsts injured by manganese- induced cytotoxicity. Biomed Sci Lett. 2018;24:357-364. https://doi.org/10.15616/BSL.2018.24.4.357
  8. Lee SH, Seo YM. Alleviating effects of Euphorbiae humifusae L. extract on the neurotoxicity induced by lead. Korean J Clin Lab Sci. 2018;50:501-510. https://doi.org/10.15324/kjcls.2018.50.4.501
  9. Ma J, Luo XD, Protiva P, Yang H, Ma C, Basile MJ, et al. Bioactive novel polyphenols from the fruit of Manikara zapota (Sapodoilla). J Nat Prod. 2003;66:983-986. https://doi.org/10.1021/np020576x
  10. Kwak JS, Seong HG. East medicinal thesaurus herb encyclopedia. Gyeonggi-do: Purnhaengbok Publishing; 2018. p303-306.
  11. Benarroch EE. Neuron-astrocyte interactions partnership for normal function and disease in the central nervous system. Mayo Clin Proc. 2005;80:1326-1338. https://doi.org/10.4065/80.10.1326
  12. Fang G, Li G, Pang C, Li W, Wang D, Liu C. Utrasound-assisted extraction of pristimerin from Celastrus orbiculatus using response surface methodology. Biol Pharmaceut Bull. 2016;b15-00664.
  13. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth. 1983;65:55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  14. AOAC. Official methods of analysis. 18th ed. Washington DC: Association of Official Analytical Chemists; 2005. Vol 45, p21-22.
  15. Nieva Moreno MI, Isla MI, Sampietro AR, Vattuone MA. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J Ethnopharmacol. 2000;71: 109-114. https://doi.org/10.1016/S0378-8741(99)00189-0
  16. Kikuzaki H, Nakatani N. Antioxidant effect of some ginger constituents. J Food Sci. 1993;58:1407-1410. https://doi/epdf/10.1111/j.1365-2621.1993.tb06194.x
  17. Stirpe F, Corte ED. The regulation of rat liver xanthine oxidase conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem. 1969;244:3855-3861. https://doi.org/10.1016/S0021-9258(17)36428-1
  18. De-Lau LML, Breteler MM. Epidemiology of Parkinson’s disease. Lan Neurol. 2006; 5:525-535. https://doi.org/10.1016/S1474-4422(06)70471-9
  19. Borenfreund E, Puerner JA. A simple quantitative procedure using monolayer culture for cytotoxicity assay (HTD/NR-90). J Tiss Cult Meth. 1985;9:7-9. https://doi.org/10.1007/BF01666038
  20. Tsou TC, Lai HJ, Yang JL. Effects of mannitol or catalase on the generation of reactive oxygen species leading to DNA damaged by chromium (VI) reduction with ascorbate. Chem Res Toxicol. 1999;12:1002-1009. https://doi.org/10.1021/tx9802264
  21. Chung JH, Rim YS, Seo YM. Protective effect of Albizzia julibrissin leaf extract on the cytotoxicity induced by cupric acetate metallic mordant. J Environ Health Sci. 2019;45:520-528. https://doi.org/10.5668/JEHS.2019.45.5.520
  22. Graefe EU, Witting J, Mueller S, Riethling AK, Uehleke B, Drewelow B, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol. 2001;41:492-499. https://doi.org/10.1177/00912700122010366
  23. Chung JH, Lee GW, Seo YM. Protective effect of Aster tataricus L. extract on the dermal cytotoxicity induced by sodium bromate, oxidant of hair dye. Biomed Sci Lett. 2019;25:348-356. https://doi.org/10.15616/BSL.2019.25.4.348