DOI QR코드

DOI QR Code

Effect of Red Ginseng on Radiation-induced Learning and Memory Impairment in Mouse

방사선 조사 마우스에서 학습기억 장애에 대한 홍삼의 효과

  • Lee, Hae-June (Korea Institute of Radiological & Medical Science) ;
  • Kim, Joong-Sun (Korea Institute of Radiological & Medical Science) ;
  • Moon, Chang-Jong (College of Veterinary Medicine, Chonnam National University, Animal Medical Center, Chonnam National University) ;
  • Kim, Jong-Choon (College of Veterinary Medicine, Chonnam National University, Animal Medical Center, Chonnam National University) ;
  • Jo, Sung-Kee (Advanced Radiation Technology Institute, KAERI) ;
  • Jang, Jong-Sik (Department of Animal Science, Kyungpook National University) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Chonnam National University, Animal Medical Center, Chonnam National University)
  • 이해준 (한국원자력의학원) ;
  • 김중선 (한국원자력의학원) ;
  • 문창종 (전남대학교 수의과대학, 전남대학교 동물의학연구소) ;
  • 김종춘 (전남대학교 수의과대학, 전남대학교 동물의학연구소) ;
  • 조성기 (한국원자력연구원 정읍 방사선과학연구소) ;
  • 장종식 (경북대학교 축산학과) ;
  • 김성호 (전남대학교 수의과대학, 전남대학교 동물의학연구소)
  • Published : 2009.06.30

Abstract

Previous studies suggest that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. In this study, whether red ginseng (RG) could attenuate memory impairment was investigated through a passive-avoidance and object recognition memory test, as well as the suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) in adult mice treated with a relatively low-dose exposure to gamma radiation (0.5 or 2.0 Gy). RG was administered intraperitonially at a dosage of 50 mg/kg of body weight, at 36 and 12 h pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg! kg of body weight/day for seven days before autopsy. In the passive-avoidance and object recognition memory test, the mice that were trained for one day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells was significantly decreased. RG treatment prior to irradiation attenuated the memory defect and blocked apoptotic death as well as a decrease in the Ki-67- and DCX-positive cells. RG may attenuate memory defect in a relatively low-dose exposure to radiation in adult mice, possibly by inhibiting the detrimental effect of irradiation on hippocampal neurogenesis.

Keywords

References

  1. Crossen JR, Garwood D, Glatstein E, Neuwelt EA. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol. 12: 627-642 (1994) https://doi.org/10.1200/JCO.1994.12.3.627
  2. Monje ML, Palmer T. Radiation injury and neurogenesis. Curr Opin Neurol. 16: 129-134 (2003) https://doi.org/10.1097/00019052-200304000-00002
  3. Strother DR, Pollack IF, Fisher PG, Hunter JV, Woo S Pomeroy SL, Rorke LB. Tumors of the central nervous system. p. 751-824. In: Pizzo PA, Pollack IF. (ed), Principles and practice of pediatric oncology. Lippincott Williams and Wilkins, Philadelphia (2002)
  4. Tada E, Parent JM, Lowenstein DH, Fike JR. X-irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats. Neuroscience 99: 33-41 (2000) https://doi.org/10.1016/S0306-4522(00)00151-2
  5. Raber J, Rola R, LeFevour A, Morhardt D, Curley J, Mizumatsu S, VandenBerg SR, Fike JR. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res. 162: 39-47 (2004) https://doi.org/10.1667/RR3206
  6. Kim JS, Lee HJ, Kim JC, Kang SS, Bae CS, Shin T, Jin JK, Kim SH, Wang H, Moon C. Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis. J Radiat Res. 49: 517-526 (2008) https://doi.org/10.1269/jrr.08020
  7. Kempermann G, Kuhn HG, Gage FH. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci USA 94: 10409-10414 (1997) https://doi.org/10.1073/pnas.94.19.10409
  8. Kim JS, Jung J, Lee HJ, Kim JC, Wang H, Kim SH, Shin T, Moon C. Differences in immunoreactivities of Ki-67 and doublecortin in the adult hippocampus in three strains of mice. Acta Histochem. 111: 150-156 (2009) https://doi.org/10.1016/j.acthis.2008.05.002
  9. Sonnenborn U, Propert Y. Ginseng (Panax ginseng C. A. Meyer). Br J Phytother. 2: 3-14 (1991)
  10. Tang W, Eisenbrand G. Panax ginseng C. A. Meyer. p.711-737. In: Chinese Drugs of Plant Origin. Springer, London (1992)
  11. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents andmultiple actions. Biochem Pharmacol. 58: 1685-1693 (1999) https://doi.org/10.1016/S0006-2952(99)00212-9
  12. Gillis CN. Panax ginseng pharmacology: a nitric oxide link. Biochem Pharmacol. 54: 1-8 (1997) https://doi.org/10.1016/S0006-2952(97)00193-7
  13. Lee HJ, Kim SR, Kim JC, Kang CM, Lee YS, Jo SK, Kim TH, Jang JS, Nah SY, Kim SH. In vivo radioprotective effect of Panax ginseng C.A. Meyer and identification of active ginsenosides. Phytother Res. 20: 392-395 (2006) https://doi.org/10.1002/ptr.1867
  14. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 11: 565-576 (2000) https://doi.org/10.1023/A:1008980200583
  15. Lee TK, Johnke RM, Allison RR, O'Brien KF, Dobbs LJ Jr. Radioprotective potential of ginseng. Mutagenesis 20: 237-243 (2005) https://doi.org/10.1093/mutage/gei041
  16. Park JD. Recent studies on the chemical constituents of Korean ginseng (Panax ginseng C. A. Meyer). Kor J Ginseng Sci. 20: 389-415 (1996)
  17. Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, PengH, Aburaya J, Ishihara K, Sakanaka M. Protection of ischemic hippocampal neurons byginsenoside Rb1, a main ingredient of ginseng root. Neurosci Res. 28: 191-200 (1997) https://doi.org/10.1016/S0168-0102(97)00041-2
  18. Jeong TC, Kim HJ, Park JI, Ha CS, Park JD, Kim SI, Roh JK. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Med. 63: 136-140 (1997) https://doi.org/10.1055/s-2006-957630
  19. Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res. 7: 181-186 (1995)
  20. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tonooka S, Samukawa K, Azuma I. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull. 18: 1197-1202 (1995) https://doi.org/10.1248/bpb.18.1197
  21. Ding DZ, Shen TK, Cui YZ. Effects of red ginseng on the congestive heart failure and its mechanism. Zhongguo Zhong Xi Yi Jie He Za Zhi 15: 325-327 (1995)
  22. Yun TK, Choi Sy' Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 4: 401-408 (1995)
  23. Samukawa K, Yamashita H, Matsuda H, Kubo M. Simultaneous analysis of ginsenosides of various ginseng radix by HPLC. Yakugaku Zasshi 115: 241-249 (1995) https://doi.org/10.1248/yakushi1947.115.3_241
  24. Li X, Guo R, Li1. Pharmacological variations of Panax ginseng C.A. Meyer during processing. Zhongguo Zhong Yao Za Zhi 16: 3-7 (1991)
  25. Kim SH, Jeong KS, Ryu SY, Kim TH. Panax ginseng prevents apoptosis in hair follicles and accelerates recovery of hair medullary cells in irradiated mice. In Vivo 12: 219-222 (1998)
  26. Kim SH, Cho CK, Yoo SY, Koh KH, Yun HG, Kim TH. In vivo radioprotective activity of Panax ginseng and diethyldithiocarbamate. In Vivo 7: 467-470 (1993)
  27. Kim TH, Lee YS, Cho CK, Park S, Choi SY, Yool SY. Protective effect of ginseng on radiation induced DNA double strand breaks and repair in murine lymphocytes. Cancer Biother Radiopharm. 11: 267-272 (1996) https://doi.org/10.1089/cbr.1996.11.267
  28. Kumar M, Sharma MK, Saxena PS, Kumar A. Radioprotective effect of Panax ginseng on the phosphatases and lipid peroxidation level in testis of swiss albino mice. Biol Pharm Bull. 26: 308-312 (2003) https://doi.org/10.1248/bpb.26.308
  29. Lee EH, Cho SY, Kim SJ, Shin ES, Chang HK, Kim CD, Yeom MH, Woe KS, Lee JS, Sim YC, Lee TR. Ginsenoside F1 protects human HaCaT keratocytes from ultraviolet-Binduced apoptosis by maintaining constant levels of Bcl-2. J Invest Dermatol. 121: 607-613 (2003) https://doi.org/10.1046/j.1523-1747.2003.12425.x
  30. Lee HJ, Kim JS, Song MS, Seo HS, Moon C, Kim JC, Jo SK, Jang JS, Kim SH. Photoprotective effect of red ginseng against ultraviolet radiation-induced chronic skindamage in the hairless mouse. Phytother Res. 23: 399-403 (2009) https://doi.org/10.1002/ptr.2640
  31. Lee HJ, Kim SR, Kim JS, Moon C, Kim JC, BaeCS, Jang JS, Jo SK, Kim SH. The effect of red ginseng on epidermal melanocytes in ultraviolet B-irradiated mice. J Ginseng Res. 30: 188-193 (2006) https://doi.org/10.5142/JGR.2006.30.4.188
  32. Lee HJ, Kim SR, Kim JS, Moon C, Kim JC, Bae CS, Jang JS, Jo SK, Kim SH. The effect of red ginseng on ultraviolet Binduced skin damages inmouse. J Ginseng Res. 30: 194-198 (2006) https://doi.org/10.5142/JGR.2006.30.4.194
  33. Zhao W, Robbins ME. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem. 16: 130-143 (2009) https://doi.org/10.2174/092986709787002790
  34. Kitts DD, Hu C. Efficacy and safety of ginseng. Pub Health Nut. 4: 473-485 (2000)
  35. Kim YK, Guo Q, Packer L. Free radical scavenging activity of red ginseng aqueous extracts. Toxicology 172: 149-156 (2002) https://doi.org/10.1016/S0300-483X(01)00585-6
  36. Kumar M, Sharma MK, Saxena PS, Kumar A. Radioprotective effect of Panax ginseng on the phosphatases and lipid peroxidation level in testes of Swiss albino mice. Biol Pharm Bull. 26: 308-312 (2003) https://doi.org/10.1248/bpb.26.308
  37. Zhang D,Yasuda T, Yu Y, Zheng P, Kawabata T, Ma Y, Okada S. Ginseng extract scavenges hydroxyl radical andprotects unsaturated fatty acids from decomposition caused by ironmediated lipid peroxidation. Free Radic BioI Med. 20: 145-150 (1996) https://doi.org/10.1016/0891-5849(95)02020-9
  38. Matsuda H, Samukawa K, Kubo M. Anti-inflammatory activity of ginsenoside Ro. Planta Med. 56: 19-23 (1990) https://doi.org/10.1055/s-2006-960875
  39. Park JS, Park EM, Kim DH, Jung K, Jung JS, Lee EJ, Hyun JW. Kang JL, Kim HS. Anti-inflammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol. 209: 40-49 (2009) https://doi.org/10.1016/j.jneuroim.2009.01.020