[논문]MPP+로 유도된 파킨슨병 세포 모델에서 Hepad S9-1의 신경세포 보호 효과

목서희; 박병준; 주인환; 박종민; 김동희

doi:10.15188/kjopp.2023.08.37.4.68

MPP+로 유도된 파킨슨병 세포 모델에서 Hepad S9-1의 신경세포 보호 효과
Neuroprotective Effect of Hepad S9-1 in MPP+-treated PC12 Cells 원문보기

동의생리병리학회지 = Journal of physiology & pathology in Korean Medicine, v.37 no.4, 2023년, pp.68 - 72

목서희 (대전대학교 한의과대학 병리학교실) , 박병준 (대전대학교 한의과대학 병리학교실) , 주인환 (대전대학교 한의과대학 병리학교실) , 박종민 (대전대학교 한의과대학 병리학교실) , 김동희 (대전대학교 한의과대학 병리학교실)

Abstract ▼ AI-Helper

Parkinson's disease is the second most common neurodegenerative disease. Levodopa has a good effect for a period of two to five years, but long-term use reduces the effectiveness of the drug and accompanies side effects. To date, there is no strategy that has been able of fundamental treatment of Parkinson's disease. We developed Hepad S9-1 composed of 5 herbal materials (Paeonia lactiflora Pallas, Uncaria sinensis Havil, Spatholobus suberectus Dunn, Panax ginseng C. A. Meyer, and Glycyrrhiza uralensis Fischer). This in vitro study was conducted to search a novel disease-modifying drug, observing the effect of Hepad S9-1, a plant derived compounds on the apoptotic process of PC12 cells which was induced by 1-methyl-4-phenylpyridinium (MPP+). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the effect of MMP+ or Hepad S9-1 on cell viability in PC12 cells. In addition, we examined cell protective effect of Hepad S9-1 in MPP+-induced PC12 cells. And gene and protein expression level of various factors that regulate apoptosis were confirmed by real-time PCR and western blot analysis. As a result of the study, Hepad S9-1 significantly inhibited MPP+-induced neuronal cell death. Also, Hepad S9-1 inhibited apoptosis-inducing Bcl-2 associated X (Bax) gene and protein expression, cytochrome C protein expression, caspase-9, caspase-7, caspase-3 and poly ADP-ribose polymerase (PARP) activation. In addition, the neuroprotective ability was objectively confirmed by up-regulating the genes and proteins expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) that defend at apoptosis. Therefore, it seems that Hepad S9-1 can be additionally applied to the treatment of Parkinson's disease to suppress the progression of dopaminergic neuronal cell death.

주제어

표/그림 (7)

표 Table 1. The prescription of Hepad S9-1
표 Table 2. Real-Time PCR Primer Sequences
표 Table 3. Primary Antibodies Used for Western Blotting
그림 Fig. 1. Cell viability of MPP+ or Hepad S9-1 in PC12 cells. The cells were treated by 100, 200, 500, and 600 μM of MPP+ or 50, 100, 200, and 400 μg/mL of Hepad S9-1 for 24 h. Treated cells were reacted by EZ-Cytox for 30 min and then absorbance were measured at 450 nm using micro plate reader. Cell viability were calculated as percentage relative to the control. The result were presented by the mean±standard error of mean from three independent experiments(Significance of results, * ; p<0.05, ** ; p<0.01, *** ; p<0.001 compared to control). (A); cell viability of MPP+, (B); cell viability of Hepad S9-1.
그림 Fig. 2. Protective effect of Hepad S9-1 in PC12 cells on MPP+ induced cytotoxicity. The cells were treated by 50, 100, 200 μg/mL of Hepad S9-1 for 1 h and were exposed to 500 μM of MPP+ for 24 h. Treated cells were reacted by EZ-Cytox for 30 min and then absorbance were measured at 450 nm using micro plate reader. Cell viability were calculated as percentage relative to the control. The result were presented by the mean±standard error of mean from three independent experiments(Significance of results, +++ : p<0.001 compared to control, ** ; p<0.01, *** ; p<0.001 compared to MPP+).
그림 Fig. 3. Effect of Hepad S9-1 on apoptosis-related gene expression level in MPP+ induced PC12 cells. The cells were treated by 50, 100, 200 μg/mL of Hepad S9-1 for 1 h and were exposed to 500 μM of MPP+ for 24 h. The mRNA expression level were measured using a real-time PCR. The result were presented by the mean±standard error of mean from three independent experiments(Significance of results, +++ : p<0.001 compared to control, * ; p<0.05, *** ; p<0.001 compared to MPP+).
그림 Fig. 4. Effect of Hepad S9-1 on apoptosis-related protein expression level in MPP+ induced PC12 cells. The cells were treated by 50, 100, 200 μg/mL of Hepad S9-1 for 1 h and were exposed to 500 μM of MPP+ for 24 h. The mRNA expression level were measured using a western blot assay. The result were presented by the mean±standard error of mean from three independent experiments(Significance of results, +++ : p <0.001 compared to control, * ; p<0.05, ** ; p<0.01, *** ; p<0.001 compared to MPP+). (A, C); protein expression level (B); graph image

참고문헌 (29)

Abbas MM, Xu Z, Tan LC. Epidemiology of Parkinson's？disease-East versus West. Movement disorders clinical？practice. 2018;5(1):14-28.

상세보기
Raza C, Anjum R. Parkinson's disease: Mechanisms,？translational models and management strategies. Life？sciences. 2019;226:77-90.
Tysnes O-B, Storstein A. Epidemiology of Parkinson's？disease. Journal of neural transmission. 2017;124:901-5.

상세보기
Radhakrishnan DM, Goyal V. Parkinson's disease: A？review. Neurology India. 2018;66(7):26.
Duwa R, Jeong J-H, Yook S. Development of？immunotherapy and nanoparticles-based strategies for？the treatment of Parkinson's disease. Journal of？Pharmaceutical Investigation. 2021;51:465-81.

상세보기
Li W-w. Botanical Therapeutics for Parkinson's Disease.？Chinese journal of integrative medicine. 2020;26(6):405-11.

상세보기
pments in the treatment of Parkinson's Disease.？F1000Research. 2020;9.
Kalia LV, Kalia SK, Lang AE. Disease-modifying？strategies for Parkinson's disease. Movement Disorders.？2015;30(11):1442-50.

상세보기
Park S-m, Lee S-h, Yin C-s, Kang M-k, Chang D-i,？Kang S-k, et al. Literature Review on Parkinson's？disease in Oriental medicine. Journal of Acupuncture？Research. 2004;21(1):202-10.
Lim SY, Kim HR, Choi YS, Lee I. Review of Current？Clinical Studies for Herbal Medicine of Parkinson's？Disease in Traditional Chinese Medicine. Journal of？Physiology & Pathology in Korean Medicine.？2016;30(5):327-37.
Zheng M, Liu C, Fan Y, Shi D, Jian W. Total glucosides？of paeony (TGP) extracted from Radix Paeoniae Alba exerts neuroprotective effects in MPTP-induced？experimental parkinsonism by regulating the？cAMP/PKA/CREB signaling pathway. Journal of？ethnopharmacology. 2019;245:112182.

상세보기
Shim JS, Kim HG, Ju MS, Choi JG, Jeong SY, Oh MS.？Effects of the hook of Uncaria rhynchophylla on？neurotoxicity in the 6-hydroxydopamine model of？Parkinson's disease. Journal of Ethnopharmacology.？2009;126(2):361-5.

상세보기
Park HR, Lee H, Lee J-J, Yim N-H, Gu M-J, Ma JY.？Protective effects of spatholobi caulis extract on？neuronal damage and focal ischemic stroke/reperfusion？injury. Molecular Neurobiology. 2018;55:4650-66.
Gonzalez-Burgos E, Fernandez-Moriano C,？Gomez-Serranillos MP. Potential neuroprotective activity？of Ginseng in Parkinson's disease: a review. Journal of？Neuroimmune Pharmacology. 2015;10:14-29.

상세보기
Park CH, Kim JH, Choi SH, Shin YS, Lee SW, Cho EJ.？Protective effects of Glycyrrhiza uralensis Radix extract？and its active compounds on H2O2-induced apoptosis？of C6 glial cells. Korean Journal of Medicinal Crop？Science. 2017;25(5):315-21.
De Lau LM, Breteler MM. Epidemiology of Parkinson's？disease. The Lancet Neurology. 2006;5(6):525-35.

상세보기
Davie CA. A review of Parkinson's disease. British？medical bulletin. 2008;86(1):109-27.

상세보기
Monzon-Sandoval J, Poggiolini I, Ilmer T, Wade-Martins？R, Webber C, Parkkinen L. Human-specific？transcriptome of ventral and dorsal midbrain dopamine？neurons. Annals of Neurology. 2020;87(6):853-68.

상세보기
Jazvinscak Jembrek M, Orsolic N, Mandic L, Sadzak A,？Segota S. Anti-oxidative, anti-inflammatory and？anti-apoptotic effects of flavonols: targeting Nrf2, NF-κB and p53 pathways in neurodegeneration. Antioxidants.？2021;10(10):1628.
Melamed E, Ziv I, Djaldetti R. Management of motor？complications in advanced Parkinson's disease.？Movement disorders: official journal of the Movement？Disorder Society. 2007;22(S17):S379-S84.
Thanvi B, Lo N, Robinson T. Levodopa-induced？dyskinesia in Parkinson's disease: clinical features,？pathogenesis, prevention and treatment. Postgraduate？medical journal. 2007;83(980):384-8.
Yuan J, Yankner BA. Apoptosis in the nervous system.？Nature. 2000;407(6805):802-9.

상세보기
Qiao C, Zhang L-X, Sun X-Y, Ding J-H, Lu M, Hu G.？Caspase-1 deficiency alleviates dopaminergic neuronal？death via inhibiting caspase-7/AIF pathway in MPTP/p？mouse model of Parkinson's disease. Molecular？Neurobiology. 2017;54:4292-302.

상세보기
Okouchi M, Ekshyyan O, Maracine M, Aw TY. Neuronal？apoptosis in neurodegeneration. Antioxidants & redox？signaling. 2007;9(8):1059-96.
Youle RJ, Strasser A. The BCL-2 protein family:？opposing activities that mediate cell death. Nature？reviews Molecular cell biology. 2008;9(1):47-59.

상세보기
Czabotar PE, Lessene G, Strasser A, Adams JM. Control？of apoptosis by the BCL-2 protein family: implications？for physiology and therapy. Nature reviews Molecular？cell biology. 2014;15(1):49-63.

상세보기
Kim T-H, Kim P-H, Jeon B-K, Yoon J-R, Woo W-H,？Mun Y-J, et al. Effect of Anemarrhenae Rhizoma？ethanol extract on apoptosis induction of HT-29 human？colon cancer cells. The Journal of Korean Medicine？Ophthalmology and Otolaryngology and Dermatology.？2011;24(1):16-24.
Erekat NS. Apoptosis and its Role in Parkinson's？Disease. Exon Publications. 2018:65-82.
Akbar AN, Borthwick NJ, Wickremasinghe RG,？Panayiotidis P, Pilling D, Bofill M, et al. Interleukin-2？receptor common γ-chain signaling cytokines regulate？activated T cell apoptosis in response to growth factor？withdrawal: Selective induction of anti-apoptotic (bcl-2,？bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene？expression. European journal of immunology.？1996;26(2):294-9.

저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증