MPP+로 유도된 파킨슨병 세포 모델에서 Hepad S9-1의 신경세포 보호 효과
Neuroprotective Effect of Hepad S9-1 in MPP+-treated PC12 Cells
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (29)
- Abbas MM, "Epidemiology of Parkinson's disease—East versus West", Movement disorders clinical practice, 5(1), pp.14~28 (2018)
- Raza C, "Parkinson's disease : Mechanisms, translational models and management strategies", Life sciences, 226, pp.77~90 (2019)
- Tysnes O-B, "Epidemiology of Parkinson’s disease", Journal of neural transmission, 124, pp.901~905 (2017)
- Radhakrishnan DM, "Parkinson's disease : A review", Neurology India, 66(7), pp.26~ (2018)
- Duwa Ramesh, "Development of immunotherapy and nanoparticles-based strategies for the treatment of Parkinson’s disease", Journal of Pharmaceutical Investigation, 51(4), pp.465~481 (2021), 한국약제학회[DOI]
- Li W-w, "Botanical Therapeutics for Parkinson’s Disease", Chinese journal of integrative medicine, 26(6), pp.405~411 (2020)
- "pments in the treatment of Parkinson's Disease", F1000Research, 9~ (2020)
- Kalia LV, "Disease‐modifying strategies for Parkinson's disease", Movement Disorders, 30(11), pp.1442~1450 (2015)
- 박상민, "파킨슨병의 한의학적 고찰 -병인병리와 침구요법을 중심으로-", Journal of Acupuncture Research, 21(1), pp.202~210 (2004), 대한침구의학회
- 임수연, "파킨슨병의 한약 치료에 대한 최신 임상연구 동향 고찰 - 2010년부터 2014년까지 중국 논문을 중심으로 -", 동의생리병리학회지, 30(5), pp.327~337 (2016), 한의병리학회[DOI]
- Zheng M, "Total glucosides of paeony (TGP) extracted from Radix Paeoniae Alba exerts neuroprotective effects in MPTP-induced experimental parkinsonism by regulating the cAMP", PKA, Journal of ethnopharmacology, pp.2019, 245[DOI]
- Shim JS, "Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease", Journal of Ethnopharmacology, 126(2), pp.361~365 (2009)
- Park HR, "Protective effects of spatholobi caulis extract on neuronal damage and focal ischemic stroke", reperfusion injury, 2018, pp.55, 4650~4666
- González-Burgos E, "Potential neuroprotective activity of Ginseng in Parkinson’s disease: a review", Journal of Neuroimmune Pharmacology, 10, pp.14~29 (2015)
- 박찬흠, "H2O2로 유도된 C6 신경교세포의 세포사멸에 대한 감초 추출물과 감초 활성물질의 보호효과", 한국약용작물학회지, 25(5), pp.315~321 (2017), 한국약용작물학회[DOI]
- De Lau LM, "Epidemiology of Parkinson's disease", The Lancet Neurology, 5(6), pp.525~535 (2006)
- Davie CA, "A review of Parkinson's disease", British medical bulletin, 86(1), pp.109~127 (2008)
- Monzón-Sandoval J, "Human‐specific transcriptome of ventral and dorsal midbrain dopamine neurons", Annals of Neurology, 87(6), pp.853~868 (2020)
- Jazvinšćak Jembrek M, "Anti-oxidative, anti-inflammatory and anti-apoptotic effects of flavonols: targeting Nrf2, NF-κB and p53 pathways in neurodegeneration", Antioxidants, 10(10), pp.1628~ (2021)
- Melamed E, "Management of motor complications in advanced Parkinson's disease", Movement disorders : official journal of the Movement Disorder Society, 22(S17), pp.S379~S384 (2007)
- Thanvi B, "Levodopa-induced dyskinesia in Parkinson’s disease: clinical features, pathogenesis, prevention and treatment", Postgraduate medical journal, 83(980), pp.384~388 (2007)
- Yuan J, "Apoptosis in the nervous system", Nature, 407(6805), pp.802~809 (2000)
- Qiao C, "Caspase-1 deficiency alleviates dopaminergic neuronal death via inhibiting caspase-7", AIF pathway in MPTP, Molecular Neurobiology, pp.2017, 54[DOI]
- Okouchi M, "Neuronal apoptosis in neurodegeneration", Antioxidants & redox signaling, 9(8), pp.1059~1096 (2007)
- Youle RJ, "The BCL-2 protein family : opposing activities that mediate cell death", Nature reviews Molecular cell biology, 9(1), pp.47~59 (2008)
- Czabotar PE, "Control of apoptosis by the BCL-2 protein family : implications for physiology and therapy", Nature reviews Molecular cell biology, 15(1), pp.49~63 (2014)
- 김태현, "知母에탄올추출물의 HT-29대장암세포 Apoptosis 유도효과", 한방안이비인후피부과학회지, 24(1), pp.16~24 (2011), 대한한방안이비인후피부과학회
- Erekat NS, "Apoptosis and its Role in Parkinson’s Disease", Exon Publications, 65~82 (2018)
- Akbar AN, "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, 26(2), pp.294~299 (1996)
