초록 ▼

본 과제는 성체 신경줄기세포의 증식과 이동, 분화, 생존을 유도하는 한약제제를 탐색하여 그 기전을 밝히고 뇌졸중 동물 모델에서 그 치료 효과를 검증하는 것을 목표로 함.
1. 후보 물질로 강활유풍탕, 목향, 황금, 천마, 황련, 구기자, 오미자, 치자, 조구등을 선정함.
2. 신경줄기세포 배양을 통하여, 천마와 quercetin이 Akt 증가를 통해 신경줄기세포의 증식을 유도함을 밝힘.
3. 구기자가 caspase-3의 cleavage 억제를 통해 칼슘에 의한 신경줄기세포의 사멸을 억제하고, 치자가 균일하게 신경세포

본 과제는 성체 신경줄기세포의 증식과 이동, 분화, 생존을 유도하는 한약제제를 탐색하여 그 기전을 밝히고 뇌졸중 동물 모델에서 그 치료 효과를 검증하는 것을 목표로 함.
1. 후보 물질로 강활유풍탕, 목향, 황금, 천마, 황련, 구기자, 오미자, 치자, 조구등을 선정함.
2. 신경줄기세포 배양을 통하여, 천마와 quercetin이 Akt 증가를 통해 신경줄기세포의 증식을 유도함을 밝힘.
3. 구기자가 caspase-3의 cleavage 억제를 통해 칼슘에 의한 신경줄기세포의 사멸을 억제하고, 치자가 균일하게 신경세포로의 분화를 안정적으로 유도할 수 있음을 밝힘.
4. 뇌졸중 동물 모델을 이용하여 천마가 뇌졸중 동물의 약간의 운동 기능 개선에 효과가 있음을 밝힘.
5. quercetin이 정상, 뇌졸중 동물 모델 모두에서 nestin 양성 세포의 수를 증가시키는 것을 통하여, 신경줄기세포의 증식을 증가시키고, BDNF 발현을 증가시킴을 확인함.

Abstract ▼

Ⅰ. Purpose for research
To search oriental medicine leading to proliferation, migration, differentiation, and survival of adult neural stem cells(NSCs),
To elucidate the therapeutic mechanism of the searched oriental medicine.
To examine the therapeutic effect of the medicine in animal mode

Ⅰ. Purpose for research
To search oriental medicine leading to proliferation, migration, differentiation, and survival of adult neural stem cells(NSCs),
To elucidate the therapeutic mechanism of the searched oriental medicine.
To examine the therapeutic effect of the medicine in animal models of stroke.
Since the stroke treatment studies using transplantation of NSCs have been tried at home and abroad, we tested whether Tangje and Danmi used in oriental medicine can activate NSCs in order to develop drugs or combination therapy for cell-based treatment of stroke.

Ⅱ. Research scope
1 Using the culture of NSCs, to screen the oriental medicine inducing proliferation, survival, migration, differentiation of NSCs.
2 Using a stroke animal model, to research whether the candidate substance lead to the proliferation/differentiation of endogenous NSCs in the brain

Ⅲ. Results
1. ganghwalyupung-tang, Mok-hyang, Hwang-guem, Chun-ma(EEGR), Hwang-ryun, Gugija, Schisandra, Chija, and Jogudeung were selected as the candidates.
2. Chun-ma(EEGR) and quercetin increased the proliferation of NSCs through increased Akt phosphorylation in the culture of NSCs.
3. Gugija inhibited the apoptosis of NSCs induced by calcium influx through inhibition of caspase-3 cleavage. Chija induced the uniform and stable differentiation of NSCs into neuronal cells.
4. Chun-ma(EEGR) had a positive effect to improve slightly the function of motor neuron in a stroke animal model.
5. Quercetin increased proliferation of NSCs ,through increasing the number of nestin-positive cells and induced the expression of BDNF in both normal and stroke model.

Ⅳ. Future Plan
1 To continue the research in order to elucidate the molecular mechanism of quercetin effects on NSCs proliferation and publish the related papers.
2. To use the candidates as the proliferation/differentiation-inducing agent for NSCs.
3. To continually study the therapeutic effect of the candidates in other neurodegenerative diseases.