DOI QR코드

DOI QR Code

화학적 저산소증이 유도하는 뇌신경세포 손상에 있어서 미성숙 진귤 과피 발효 추출물의 보호 효과

Anti-apoptotic effect of fermented Citrus sunki peel extract on chemical hypoxia-induced neuronal injury

  • 투고 : 2015.08.06
  • 심사 : 2015.09.03
  • 발행 : 2015.10.31

초록

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.

키워드

참고문헌

  1. World Health Organization (CH). The top 10 causes of death [Internet]. Geneva: World Health Organization; 2013 [updated 2014 May; cited 2015 Mar 11]. Available from: http://www.who.int/mediacentre/factsheets/fs310/en/.
  2. Statistics Korea. 2013 Cause of death statistics [Internet]. Daejeon: Statistics Korea; 2014 [cited 2014 Sep 23]. Available from: http://kostat.go.kr/portal/korea/kor_nw/2/6/2/index.board.
  3. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke 2009; 40(5): e331-e339. https://doi.org/10.1161/STROKEAHA.108.531632
  4. Fan X, Jiang Y, Yu Z, Yuan J, Sun X, Xiang S, Lo EH, Wang X. Combination approaches to attenuate hemorrhagic transformation after tPA thrombolytic therapy in patients with poststroke hyperglycemia/diabetes. Adv Pharmacol 2014; 71: 391-410. https://doi.org/10.1016/bs.apha.2014.06.007
  5. Ghosh N, Ghosh R, Bhat ZA, Mandal V, Bachar SC, Nima ND, Sunday OO, Mandal SC. Advances in herbal medicine for treatment of ischemic brain injury. Nat Prod Commun 2014; 9(7): 1045-1055.
  6. Lopez MS, Dempsey RJ, Vemuganti R. Resveratrol neuroprotection in stroke and traumatic CNS injury. Neurochem Int. Forthcoming 2015.
  7. Mikami Y, Yamazawa T. Chlorogenic acid, a polyphenol in coffee, protects neurons against glutamate neurotoxicity. Life Sci. Forthcoming 2015.
  8. Yasuda N, Ishii T, Oyama D, Fukuta T, Agato Y, Sato A, Shimizu K, Asai T, Asakawa T, Kan T, Yamada S, Ohizumi Y, Oku N. Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats. Brain Res 2014; 1559: 46-54. https://doi.org/10.1016/j.brainres.2014.02.007
  9. Yabuki Y, Ohizumi Y, Yokosuka A, Mimaki Y, Fukunaga K. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice. Neuroscience 2014; 259: 126-141. https://doi.org/10.1016/j.neuroscience.2013.11.051
  10. Onozuka H, Nakajima A, Matsuzaki K, Shin RW, Ogino K, Saigusa D, Tetsu N, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y. Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease. J Pharmacol Exp Ther 2008; 326(3): 739-744. https://doi.org/10.1124/jpet.108.140293
  11. Shin HS, Kang SI, Ko HC, Kim HM, Hong YS, Yoon SA, Kim SJ. Anti-inflammatory effect of the immature peel extract of Jinkyool (Citrus sunki Hort. ex Tanaka). Food Sci Biotechnol 2011; 20(5): 1235-1241. https://doi.org/10.1007/s10068-011-0170-y
  12. Kim YD, Senevirathne M, Koh KS, Jeon YJ, Kim SH. Reactive oxygen species scavenging activity of Jeju native citrus peel during maturation. J Korean Soc Food Sci Nutr 2009; 38(4): 462-469. https://doi.org/10.3746/jkfn.2009.38.4.462
  13. Moon SW, Kang SH, Jin YJ, Park JG, Lee YD, Lee YK, Park DB, Kim SJ. Fermentation of Citrus unshiu Marc. and functional characteristics of the fermented products. Korean J Food Sci Technol 2004; 36(4): 669-676.
  14. Kang SI, Shin HS, Kim HM, Hong YS, Yoon SA, Kang SW, Kim JH, Kim MH, Ko HC, Kim SJ. Immature Citrus sunki peel extract exhibits antiobesity effects by beta-oxidation and lipolysis in highfat diet-induced obese mice. Biol Pharm Bull 2012; 35(2): 223-230. https://doi.org/10.1248/bpb.35.223
  15. Cui ZG, Kim BY, Kang SH, Lee YJ, Lee DH, Lee YK, Park DB. Fermented peel of Citrus sunki Hort ex Tanaka promotes ethanol metabolism and suppresses body fat accumulation. Food Sci Biotechnol 2007; 16(2): 311-314.
  16. Lan A, Xu W, Zhang H, Hua X, Zheng D, Guo R, Shen N, Hu F, Feng J, Liu D. Inhibition of ROS-activated p38MAPK pathway is involved in the protective effect of H2S against chemical hypoxiainduced inflammation in PC12 cells. Neurochem Res 2013; 38(7): 1454-1466. https://doi.org/10.1007/s11064-013-1044-x
  17. Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondriadependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 2013; 87(7): 1157-1180. https://doi.org/10.1007/s00204-013-1034-4
  18. Ho SC, Kuo CT. Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel (Citri reticulatae pericarpium). Food Chem Toxicol 2014; 71: 176-182. https://doi.org/10.1016/j.fct.2014.06.014
  19. Jung JY, Mo HC, Yang KH, Jeong YJ, Yoo HG, Choi NK, Oh WM, Oh HK, Kim SH, Lee JH, Kim HJ, Kim WJ. Inhibition by epigallocatechin gallate of CoCl2-induced apoptosis in rat PC12 cells. Life Sci 2007; 80(15): 1355-1363. https://doi.org/10.1016/j.lfs.2006.11.033
  20. Jung JY, Roh KH, Jeong YJ, Kim SH, Lee EJ, Kim MS, Oh WM, Oh HK, Kim WJ. Estradiol protects PC12 cells against CoCl2-induced apoptosis. Brain Res Bull 2008; 76(6): 579-585. https://doi.org/10.1016/j.brainresbull.2008.04.006
  21. Zeng KW, Wang XM, Ko H, Yang HO. Neuroprotective effect of modified Wu-Zi-Yan-Zong granule, a traditional Chinese herbal medicine, on CoCl2-induced PC12 cells. J Ethnopharmacol 2010; 130(1): 13-18. https://doi.org/10.1016/j.jep.2010.03.018
  22. Cervellati F, Cervellati C, Romani A, Cremonini E, Sticozzi C, Belmonte G, Pessina F, Valacchi G. Hypoxia induces cell damage via oxidative stress in retinal epithelial cells. Free Radic Res 2014; 48(3): 303-312. https://doi.org/10.3109/10715762.2013.867484
  23. Wang LX, Zeng JP, Wei XB, Wang FW, Liu ZP, Zhang XM. Effects of scutellarin on apoptosis induced by cobalt chloride in PC12 cells. Chin J Physiol 2007; 50(6): 301-307.

피인용 문헌

  1. Optimization of Alcohol Metabolic Enzyme Activity of an Extract of Citrus sunki Hort. Tanaka Peel by Response Surface Methodology vol.50, pp.7, 2021, https://doi.org/10.3746/jkfn.2021.50.7.707