Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

Cognitive improvement effects of Momordica charantia in amyloid beta-induced Alzheimer's disease mouse model

여주의 amyloid beta 유도 알츠하이머질환 동물 모델에서 인지능력 개선 효과

  • Sin, Seung Mi (Anti-Aging Research Group, Gyeongnam Oriental Anti-Aging Institute) ;
  • Kim, Ji Hyun (Department of Food Science, Gyeongsang National University) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Hyun Young (Department of Food Science, Gyeongsang National University)
  • Received : 2021.07.14
  • Accepted : 2021.08.24
  • Published : 2021.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ25-35-induced cognitive impairment.

뇌 내 amyloid beta (Aβ) 축적으로 인한 신경독성은 산화적 스트레스를 야기하여 알츠하이머 질환(Alzheimer's disease, AD)을 유도하는 것으로 알려져 있다. 본 연구는 여주(Momordica charantia L.)의 활성분획물인 butanol (BuOH) 분획물의 Aβ25-35 유도 AD 동물모델에서 인지능 개선 효과에 대해 연구하였다. T-미로 실험 및 물체인지실험을 통해서 여주 BuOH 분획물 100 및 200 mg/kg/day 농도 투여군은 AD를 유도한 control군에 비해 유의적으로 새로운 경로와 물체를 탐색하는 비율이 감소되어 공간인지 및 물체인지능력 개선 효과를 확인하였다. 수중미로실험을 통해 학습·기억력에 미치는 효과를 측정한 결과, 여주 BuOH 분획물 투여군은 훈련을 반복할수록 숨겨진 도피대를 찾아가는 시간이 감소함을 통해 학습·기억력 개선 효과를 나타내었다. 여주 BuOH 분획물이 산화적 스트레스 개선 효과에 미치는 효과를 확인하기 위해 뇌, 간, 신장 조직에서 지질과 산화 함량 및 nitric oxideNO 생성량을 측정하였다. 여주 BuOH 분획물을 처리한 군은 Aβ25-35를 주입한 control군에 비해 유의적으로 뇌, 간, 신장 조직에서 지질과산화 함량 및 NO 생성량이 감소되어 산화적 스트레스 개선 효과를 확인하였다. 따라서 본 연구는 여주 BuOH 분획물이 Aβ25-35 유도 AD 동물모델에서 산화적 스트레스 개선을 통해 인지능력 개선 효과를 나타냄을 확인하였으며, 이에 따라 여주는 AD 예방 및 개선용 소재로써의 가능성이 있는 것으로 사료된다.

Keywords

Acknowledgement

이 논문은 2020~2021년도 경상국립대학교 대학회계 연구비 지원에 의하여 연구되었음.

References

  1. Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M (2019) Alzheimer's disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine 14: 5541-5554. doi: 10.2147/IJN.S200490
  2. Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM (2016) Alzheimer's disease. Lancet 388: 505-517. doi: 10.1016/S0140-6736(15)01124-1
  3. A Armstrong R (2019) Risk factors for Alzheimer's disease. Folia Neuropathol 57: 87-105. doi: 10.5114/fn.2019.85929
  4. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE (2017) Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 38: 1205-1235. doi: 10.1038/aps.2017.28
  5. 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 Biol 14: 450-464. doi: 10.1016/j.redox.2017.10.014
  6. Chen Z, Zhong C (2014) Oxidative stress in Alzheimer's disease. Neurosci Bull 30: 271-281. doi: 10.1007/s12264-013-1423-y
  7. Kim GH, Kim JE, Rhie SJ, Yoon S (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 24: 325-340. doi: 10.5607/en.2015.24.4.325
  8. Long JM, Holtzman DM (2019) Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell 179: 312-339. doi: 10.1016/j.cell.2019.09.001
  9. Ishiura S, Yoshida T (2019) Plant-based vaccines for Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci 95: 290-294. doi: 10.2183/pjab.95.020
  10. Gurbuz I, Akyuz C, Yesilada E, Sener B (2000) Anti-ulcerogenic effect of Momordica charantia L. fruits on various ulcer models in rats. J Ethnopharm 71: 77-82. doi: 0.1016/s0378-8741(99)00178-6 https://doi.org/10.1016/s0378-8741(99)00178-6
  11. Oyedapo OO, Araba BG (2001) Stimulation of protein biosynthesis in rat hepatocytes by extracts of Momordica charantia. Phytother Res 15: 95-98. doi: 10.1002/ptr.682
  12. Grover JK, Yadav SP (2004) Pharmacological actions and potential uses of Momordica charantia: a review. J. Ethnopharm 93: 123-132. doi: 10.1016/j.jep.2004.03.035
  13. Jia S, Shen M, Zhang F, Xie J (2017) Recent advances in Momordica charantia: functional components and biological activities. Int J Mol Sci 18: 2555. doi: 10.3390/ijms18122555
  14. Dandawate PR, Subramaniam D, Padhye SB, Anant S (2016) Bitter melon: a panacea for inflammation and cancer. Chin J Nat Med 14: 81-100. doi: 10.1016/S1875-5364(16)60002-X
  15. Kim KB, Lee S, Heo JH, Kim J (2017) Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells. J Nutr Health 50: 415-425. doi: 10.4163/jnh.2017.50.5.415
  16. Joshi A, Soni P, Malviya S, Kharia A (2017) Memory enhancing activity of Momordica charantia by scopolamine induced amnesia in rats. IJCAP 2: 11-18
  17. Sin SM, Mok SY, Lee S, Cho KM, Cho EJ, Kim HY (2011) Protective effect of bitter melon (Momordica charantia) against oxidative stress. Cancer Prev Res 16: 86-92
  18. Sin SM, Mok S-Y, Lee S, Cho KM, Cho EJ, Kim HY (2012) Antiinflammatory effect of bitter melon (Momordica charantia) in RAW 264.7 cell. Cancer Prev Res 17: 56-61
  19. Laursen SE, Belknap JK (1986) Intracerebroventricular injections in mice. Some methodological refinements. J Pharmacol Methods 16: 355-357. doi: 10.1016/0160-5402(86)90038-0
  20. Montgomery KC (1952) A test of two explanations of spontaneous alternation. J Comp Physiol Psychol 45: 287-293. doi: 10.1037/h0058118
  21. Bevins RA, Besheer J (2006) Object recognition in rats and mice: a onetrial non-matching-to-sample learning task to study 'recognition memory'. Nat Protoc 1: 1306-1311. doi: 10.1038/nprot.2006.205
  22. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47-60. doi: 10.1016/0165-0270(84)90007-4
  23. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358. doi: 10.1016/0003-2697(79)90738-3
  24. Schmidt HH, Warner TD, Nakane M, Forstermann U, Murad F (1992) Regulation and subcellular location of nitrogen oxide synthases in RAW264.7 macrophages. Mol Pharmacol 41: 615-624
  25. Lee AY, Hwang BR, Lee MH, Lee S, Cho EJ (2016) Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β25-35 induced impairment of cognition and memory function. Nutr Res Pract 10: 274-281. doi: 10.4162/nrp.2016.10.3.274
  26. Choi JR, Kim JH, Lee S, Cho EJ, Kim HY (2020) Protective effects of protocatechuic acid against cognitive impairment in an amyloid beta-induced Alzheimer's disease mouse model. Food Chem Toxicol 144: 111571. doi: 10.1016/j.fct.2020.111571
  27. Butterfield DA, Boyd-Kimball D (2018) Oxidative stress, amyloid-β peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer's disease. J Alzheimers Dis 62: 1345-1367. doi: 10.3233/JAD-170543.
  28. Butterfield DA, Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32: 1050-1060. doi: 10.1016/s0891-5849(02)00794-3
  29. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39: 73-82. doi: 10.1080/01616412.2016.1251711
  30. Malik ZA, Singh M, Sharma PL (2011) Neuroprotective effect of Momordica charantia in global cerebral ischemia and reperfusion induced neuronal damage in diabetic mice. J Ethnopharmacol 133: 729-734. doi: 10.1016/j.jep.2010.10.061
  31. Kim KB, Lee S, Kang I, Kim JH (2018) Momordica charantia ethanol extract attenuates H2O2-induced cell death by its antioxidant and antiapoptotic properties in human neuroblastoma SK-N-MC cells. Nutrients 10: 1368. doi: 10.3390/nu10101368
  32. Nerurkar PV, Johns LM, Buesa LM, Kipyakwai G, Volper E, Sato R, Shah P, Feher D, Williams PG, Nerurkar VR (2011) Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. J Neuroinflammation 8: 64. doi: 10.1186/1742-2094-8-64
  33. Rosselli M, Keller PJ, Dubey RK (1998) Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 4: 3-24. doi: 10.1093/humupd/4.1.3
  34. Picon-Pages P, Garcia-Buendia J, Munoz FJ (2019) Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis 1865: 1949-1967. doi: 10.1016/j.bbadis.2018.11.007
  35. Kim J-H, Choi JR, Cho EJ, Kim HY (2020) Protective effect of protocatechuic acid, phenolic compound of Momordica charantia, against oxidative stress and neuroinflammation in C6 glial cell. J Korean Med Obes Res 20: 10-19. doi: 10.15429/jkomor.2020.20.1
  36. Gong J, Sun F, Li Y, Zhou X, Duan Z, Duan F, Zhao L, Chen H, Qi S, Shen J (2015) Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway. Neuro-pharmacology 91: 123-134. doi: 10.1016/j.neuropharm.2014.11.020