• 생약학회지
• /
• 제42권2호
• /
• pp.175-181
• /
• 2011

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• 생약학회지
• /
• 제47권3호
• /
• pp.211-216
• /
• 2016

In the course of our continuing search for biologically active components from Korean medicinal plants, we isolated the main compound, luteolin 5-glucoside from aqueous fraction of Ajuga spectabilis. The structure was elucidated by the basis of $^1H$ and $^{13}C$ NMR and TOF ESI-MS data. Quantitative analysis of luteolin 5-glucoside was carried out on a XBridge C18 column ($S-5{\mu}m$, $4.6{\times}250mm$) with gradient elution composed of acetonitrile:water. The results exhibit that the average content of main compound in A. spectabilis were 0.048%. Oxidative stress plays a major role Alzheimer's disease (AD) and other neurodogenerative disease. AD is major health problem and there is currently no clinically accepted treatment to cure or stop its progression. Pretreatment with luteolin 5-glucoside markedly attenuated $H_2O_2$-induced cell viability loss in a dose-dependent manner. Luteolin 5-glucoside also inhibited the formation of intracellular reactive oxygen species in SH-SY5Y. The results suggest that luteolin 5-glucoside from A. spectabilis has protective effects against oxidative stress-induced cytotoxicity, which might be a potential therapeutic compound for treating and/or preventing neurodegenerative disease implicated with oxidative stress.

• Journal of Acupuncture Research
• /
• 제32권1호
• /
• pp.23-36
• /
• 2015

Objectives : This study was designed to investigate the neuroprotective effects of Hominis-Placenta (HP)on dopaminergic neurons. Methods : We examined the effect of invitro administration of HP against 1-methyl-4-phenylpyridinium( MPP+)-induced dopaminergic cell loss in primary mesencephalic culture and also used behavioral tests and performed analysis in the striatum and the substantia nigra of mouse brain, to confirm the effect of HP on dopaminergic neurons in an invivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model. Animals were assigned to four groups: (1) Group 1(vehicle-treatedgroup), (2) Group 2(MPTPonlytreated group), (3) Group 3(MPTP+ saline-treated/$ST_{36}$ group), and (4) Group 4(MPTP+HP-treated/$ST_{36}$ group). HP at $20{\mu}L$ of 48 mg/kg dose was injected at $ST_{36}$ for 4 weeks at 2-day intervals. MPTP in saline was injected intraperitoneally each day for 5 days from the $8_{th}$ treatment of HP. We performed the pole test and rota-rod test on the first and seventh day after the last MPTP injection. To investigate the effect of HP on dopaminergic neurons, we performed analysis in the striatum and the substantia nigra of mouse brain after treatment with HP and/or MPTP. Results : Treatment with HP had no influence on cell proliferation and caused no cell toxicity in $PC_{12}$ and $HT_{22}$ cells. Our study showed that HP significantly prevented cell loss and protected neurites against MPP+ toxicity. Although the invivo treatment of HP herbal acupuncture at $ST_{36}$ showed a tendency to improve movement ability and protected dopaminergic cells and fibers in the substantia nigra and the striatum, it did not show significant changes compared with the MPTP treated group. Conclusions : These data suggest that HP could be a potential treatment strategy in neurodegenerative diseases such as Parkinson's disease.

• Nuclear Medicine and Molecular Imaging
• /
• 제41권2호
• /
• pp.141-151
• /
• 2007

파킨슨병은 노년층에 가장 흔한 퇴행성 뇌질환 중의 하나로 진행성핵상마비, 다중계 위축, 루이체 치매 등과 같은 비전형 파킨슨병과 임상적으로 감별이 어려울 수 있다. 파킨슨병과 비전형 파킨슨병의 감별은 치료방침 결정과 예후평가뿐만 아니라 파킨슨병의 원인과 병태생리를 연구하고 새로운 치료법 개발에 있어서도 매우 중요하다. 파킨슨병과 비전형 파킨슨병과 같이 파킨슨 증후군을 유발하는 질환은 선조체내 도파민 신경의 퇴행성 변화를 흔히 동반하지만 병태생리학적으로 서로 다른 뇌피질 및 피질하 구조물에서의 신경세포 소실을 동반하고 있다. 따라서 국소 시냅스 활성도와 신경 및 시냅스의 손상, 그리고 원발병변과 기능적으로 연결된 원격부위의 기능이상 등을 대변하는 뇌포도당 대사를 F-18FDG PET으로 평가하는 것은 파킨슨 병의 감별진단과 병태생리를 평가하는데 유용하다.

• 한국융합학회논문지
• /
• 제11권3호
• /
• pp.135-143
• /
• 2020

파킨슨병 (PD)은 3대 노인성 신경퇴행질환 중 하나로서, 인구 고령화에 따라 전 세계적으로 발병률이 증가하고 있는 질환이다. 파킨슨병 환자의 수는 1990년 3백만 명에서 2015년 620만 명으로 증가했으며 2040년까지 1,240만명으로 증가할 것으로 예측된다. 아직까지 파킨슨병의 근본적인 치료는 정립되지 못하였으나, 화합물, 유전자, 항체, 줄기세포 등 다양한 과학적인 방법을 이용한 치료제 개발이 지속적으로 시도되고 있다. 본 연구에서는 파킨슨병 치료제 연구분야의 최신 기술 동향 및 기술 융합 현황을 파악하기 위해, 글로벌 특허정보를 활용하여 총 6개의 세부기술로 분류하였으며, 연도별, 국가별, 출원인별, 세부기술별 동향, 기술경쟁력 수준, 이종 간 기술 융합 수준을 분석하였다. 본 연구는 파킨슨병 치료제 관련 기술의 현재 기술 수준 및 기술 융합 현황을 파악하고, 향후 파킨슨병 치료제 관련 연구개발 방향성 설정 및 전략 수립을 위한 기초자료로 활용될 수 있을 것이다.

• Biomolecules & Therapeutics
• /
• 제28권1호
• /
• pp.74-82
• /
• 2020

Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

• 사상체질의학회지
• /
• 제25권3호
• /
• pp.208-217
• /
• 2013

Objectives Modified Yeolda-Hanso tang (MYH) is a traditional herbal formula in Korea for various diseases. MYH is containing the 10 herbs : Pueraria lobata (Willd.) Ohwi, Angelica tenuissima Nakai, Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L., Polygala tenuifolia (Willd), Acorus gramineus Soland and Dimocarpus longan Lour. The 10 herbs is constituted as a ratio of the 6:4:2:1:2:2:2:4:6:6. We investigated neuroprotective effects of MYH on human neuroblastoma SH-SY5Y cells and evaluated the ability of MYH to prevent and treat for neurodegenerative diseases such as Parkinson's disease via basal autophagy enhancement. Methods Pharmacological induction of Autophagy by MYH in SH-SY5Y cells: Induction of autophagy by MYH in human neuroblastoma SH-SY5Y cells was carreid out by immunoblot analysis with several autophagy markers. SH-SY5Y cells were treated with MYH at the concentration of 400 and $800{\mu}g/ml$ for 24 hr. Specifically, the autophagosome proteins LC3 II and Atg5 levels were increased and autophagy pathway related proteins such as beclin-1, PI3 Kinase class III protein, ULK1, mTOR and AMPK were activated. Conclusions MYH can enhance the induction of autophagy through key regulator AMPK, mTOR, and Beclin-1 and it should be considered as a possible candidate of neuroprotective agents for such as Parkinson's disease.

• International Neurourology Journal
• /
• 제22권4호
• /
• pp.237-245
• /
• 2018

Purpose: Presenilins are functionally important components of ${\gamma}$-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of ${\gamma}$-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. Methods: To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. Results: The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. Conclusions: Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer.

• 농업과학연구
• /
• 제46권2호
• /
• pp.369-379
• /
• 2019

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with age, and amyloid beta ($A{\beta}$) is known to cause Alzheimer's disease. In the present study, we investigated the protective effects of Cirsium japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells. The cells treated with $A{\beta}_{25-35}$ showed a decrease in cell viability and an increase in reactive oxygen species (ROS) production compared with the non-treated cells. However, the cells treated with the C. japonicum var. maackii extract and its fractions increased the cell viability and inhibited the $A{\beta}$-induced ROS production. These results demonstrate the neuroprotective effects of C. japonicum var. maackii against $A{\beta}$. To further examine the protective mechanism, we measured inflammation and apoptosis related protein expressions. The cells treated with extract and fractions from C. japonicum var. maackii down-regulated inflammatory related proteins such as cyclooxygenase-2, interleukin $(IL)-1{\beta}$, and IL-6, and attenuated apoptosis related proteins including B-cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio. In particular, the ethanol and ethylacetate fraction exhibited higher inhibitory effect against ROS production and apoptosis-related protein expressions among the extract and the other fractions. Therefore, this study demonstrated the protective effects of C. japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells through the regulation of oxidative stress, inflammation, and apoptosis, suggesting that it might have potential as a therapeutic for AD.

• Biomolecules & Therapeutics
• /
• 제29권5호
• /
• pp.483-491
• /
• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.