Intranasal Administration of Melanin-Concentrating Hormone Reduces Stress-Induced Anxiety- and Depressive-Like Behaviors in Rodents

오주영,류천봉,Cai Hua,정하진,장재환,전송희,박히준 한국뇌신경과학회 2020 Experimental Neurobiology Vol.29 No.6

Major depressive disorder is a complex neuropsychiatric disorder with few treatment options. Non-targeted antidepressants have low efficacy and can induce series of side effects. While a neuropeptide, melanin-concentrating hormone (MCH), is known to exhibit regulator of affective state, no study to date has assessed the anti-depressive effects of MCH in a stress-induced depression model. This study aimed to evaluate the pharmacological effects of intranasal administration of MCH on depression-related behavior in stressed rats and mice. Using a number of behavioral tests, we found that MCH treatment significantly decreased anxiety- and depressive-like behaviors induced by stress. Notably, the effects of MCH were equivalent to those of fluoxetine. MCH treatment also restored the activity of the mammalian target of rapamycin (mTOR) signaling pathway and normalized the levels of synaptic proteins, including postsynaptic density 95, glutamate receptor 1, and synapsin 1, which were all downregulated by stress. Interestingly, the protective effects of MCH were blocked by the mTOR inhibitor, rapamycin. These results suggest that MCH exhibits antidepressant properties by modulating the mTOR pathway. Altogether, this study provides an insight into the molecular mechanisms involved in the antidepressant-like effects of MCH, thereby paving the way for the future clinical application of MCH.

SIP-3 한약 처방 및 도네페질의 병용 치료: 아밀로이드 베타로유도된 알츠하이머병 생쥐 모델에서의 NGS 연구

오영제,송수진,류천봉,손태권,김근우,구병수 대한한방신경정신과학회 2019 동의신경정신과학회지 Vol.30 No.4

Objectives: Alzheimer’s disease (AD) is a complex disease accompanied by slow impairment of memory and coordination leading to behavioral changes. To date, the only treatment option is to delay the progress of the disease. The purpose of this study was to investigate the synergistic effects of combination treatment with donepezil and three herbal extracts SIP-3 in the AD mouse model induced by amyloid- β (Aβ). Methods: We tested SIP-3 extracts for the cytotoxicity on Aβ-treated SH-SY5Y cells. Then the synergistic effects of SIP-3 and donepezil were evaluated in the AD mouse model using animal experiments and the next generation sequencing (NGS) study. Results: We found that co-treatment with SIP-3 extracts and donepezil increased the viability in Aβ- treated SH-SY5Y cells. The beneficial effects of the co-treatment were also observed in the Aβ-induced AD mouse model. The NGS study was performed to show that the co-treatment of SIP-3 and donepezil restored the disease phenotype closely to the normal level in the AD mouse model in terms of mRNA expression. However, the phenotypes were only partially restored. Conclusions: This study suggests that the combination treatment has a potential to be used for the treatment of AD. However, longer periods of treatment may be required.

SH-SY5Y 세포에서 도네페질과 병용투여시 신경보호 효과를 나타내는 한약재의 in vitro 선별 연구

송수진 ( Sue-jin Song ),류천봉 ( Quan Feng Liu ),홍민호 ( Min-ho Hong ),김근우 ( Geun-woo Kim ),구병수 ( Byung-soo Koo ) 대한한방신경정신과학회 2019 동의신경정신과학회지 Vol.30 No.3

Objectives: The purpose of this study was to evaluate the neuroprotective effects of donepezil and 33 kinds of herbal extract combinations in SH-SY5Y cells with Aβ _25-35 treatment. Methods: MTT assay was performed to measure the cell viability of each herbal extract combined with donepezil against Aβ-induced neurotoxicity. The most active extracts were then subjected to assess the effects on CREB phosphorylation and COX-2 expressions through the western blot analysis. Results: There were eight herbal extracts representing significant increase on the cell viability: 1) Erycibe obtusifolia, 2) Polygonum multiflorum, 3) Polygala tenuifolia, 4) Illicium verum, 5) Santalum album, 6) Loranthus parasticus, 7) Platycladus orientalis, and 8) Zanthoxylum piperitum. Especially, when Santalum album and donepezil were treated together, the phosphorylation of CREB significantly increased and COX-2 protein expression was significantly inhibited. Conclusions: Among the screened herbal extracts, combination treatment of each of the eight herbs and donepezil showed neuroprotective effects in SH-SY5Y cells. Additionally, the combination of Santalum album and donepezil suggested cognitive improvement by up-regulation of p-CREB and down-regulation of COX-2.

ADHD 동물모델에서 가감청심연자탕의 효과에 관한 실험연구

오영제 ( Young-je Oh ),류천봉 ( Quan Feng Liu ),김만기 ( Man-gi Kim ),홍민호 ( Min-ho Hong ),김근우 ( Geun-woo Kim ),구병수 ( Byung-soo Koo ) 대한한방신경정신과학회 2020 동의신경정신과학회지 Vol.31 No.3

Objectives: The purpose of this study was to experimentally assess the effects of Chengsimyeonjatanggagam extracts in the animal model regarding ADHD related symptoms and indicators. Methods: The experimental group was classified into the normal group (WKY rat) in 7, the control group (SHR rat) in 7, the low-concentration group of herbal medicines (SHR rat) in 7, and the highconcentration group of herbal medicines (SHR rat) in 7 by random sampling. The open field test was conducted three times on the 7th, 14th, and 21st days during the oral medication. After that, Y-maze test, intestinal permeability verification (L/M ratio), and Western blotting (CDK expression in the cerebral cortex) were performed in sequence. Results: The Chengsimyeonjatang-gagam extracts reduced the activity distance in the SHR rat at 21 days in the low and high concentration groups by the open field test. It also reduced the cross-action rate in the low and high concentration groups by the Y-maze test. And the low concentration group showed 52.3% decrease in the L/M ratio compared to the SHR group. Finally, the CDK5 protein significantly increased in the low and high concentration groups. Conclusions: This study suggests that the Chengsimyeonjatang-gagam extracts have potential to be used for the treatment of ADHD.

홍삼 복합 추출물의 AMPK 활성화를 통한 고지혈증 개선

정하진(Ha Jin Jeong),오승택(Seung Tack Oh),류천봉(Quan Feng Liu),최유라(Yura Choi),이성미(Seoungmi Lee),전송희(Songhee Jeon) 한국식품영양과학회 2017 한국식품영양과학회지 Vol.46 No.8

당 및 지질 대사 조절의 이상으로 인한 대사성 질환 중의 하나인 고지혈증은 현대사회에서 급격하게 증가하고 있다. 이러한 문제를 해결하기 위하여 부작용이 적은 천연물을 사용하는 사례들이 급증하고 있는데, 특히 이 연구에서는 초미세 분말을 첨가한 홍삼을 이용하여 지방세포 및 쥐 혈액, 간, 그리고 지방조직에서 지질, 콜레스테롤, 당, 과산화 수치를 확인함으로써 홍삼의 효능을 관찰하였다. 세포 실험 결과, 특정한 홍삼 농도(50 μg/mL)에서 지질 형성을 미세하게 억제하고 있음을 알 수 있으며, 동물 실험에서도 마찬가지로 저농도의 홍삼을 처리하였을 때 혈중 총 콜레스테롤 수치가 가장 감소하였고 HDL-콜레스테롤 수치 또한 증가하는 것으로 밝혀졌으며, 이는 심혈관위험지수 및 동맥경화지수를 낮춰준다. 그뿐만 아니라 저농도 홍삼 식이법 시행군에서 지질대사 관련 단백질인 AMPK의 발현량이 증가하였는데, 이는 특정 농도의 홍삼이 AMPK 활성화를 높임으로써 지방 및 콜레스테롤 합성 억제를 돕는 것으로 판단된다. 따라서 본 연구는 홍삼이 대사성 질환인 고지혈증 치료 및 예방에 도움을 주는 천연물 후보임을 시사하는 바이다. Hyperlipidemia is known as a glucose and lipid metabolism-related disorder that is increasing in incidence in modern society. Red ginseng (RG) is a natural herb candidate with a positive effect on regulation of cholesterol and lipids. To observe the effects of RG on regulation of lipids, cholesterol, glucose, and oxidative stress, we examined the in vitro and in vivo effects of Chamdahan RG on differentiated 3T3-L1 adipocytes and high-fat diet-fed mice. RG (50 μg/mL) significantly inhibited lipid synthesis in 3T3-L1 cells. In addition, a low concentration of RG (880 mg/kg/d) resulted in the lowest total blood cholesterol level. Moreover, high density lipoprotein-cholesterol quantity increased in RG-treated groups, consequently lowering the cardiovascular risk factor and atherosclerosis index. Moreover, RG increased activity of AMP-activated protein kinase, as a regulator of lipid and cholesterol synthesis, in adipose and liver tissues. Cumulatively, this paper suggests that RG has a positive effect on reducing the amounts of cholesterol and lipids and may be a good candidate for treating hyperlipidemia.