• Korean Journal of Medicinal Crop Science
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• v.17 no.6
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• pp.388-396
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• 2009

The present study investigated an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcuma longae radix, Phellinus linteus, and Scutellariae radix for possible neuroprotective effects on neurotoxicity induced by amyloid $\beta$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to $10\;{\mu}M$ $A{\beta}$ (25-35) for 36 h induced neuronal apoptotic death. At $1-50\;{\mu}g/m{\ell}$, HS0608 inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $A{\beta}$ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol $A{\beta}$ (25-35) was inhibited by chronic treatment with HS0608 (25, 50 and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test. From these results, we suggest that the antidementia effect of HS0608 is due to its neuroprotective effect against $A{\beta}$ (25-35)-induced neurotoxicity and that HS0608 may have a therapeutic role in preventing the progression of Alzheimer's disease.

• Korean Journal of Medicinal Crop Science
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• v.22 no.2
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• pp.105-112
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• 2014

The present study investigated an ethanol extract (SSB) of a mixture of three medicinal plants of Vitis amurensis, Aralia cordata, and Glycyrrhizae radix for possible neuroprotective effects on neurotoxicity induced by Amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to $15{\mu}M$ $A{\beta}$ (25-35) for 36 h induced neuronal apoptotic death. At $1-30{\mu}g/m{\ell}$, SSB inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $A{\beta}$ (25-35) in cultured cortical neurons. Memory impairment and increase of acetylcholinesterase activity induced by intracerebroventricular injection of mice with 16 nmol $A{\beta}$ (25-35) was inhibited by chronic treatment with SSB (25, 50 and 100 mg/kg, p.o., for 8 days). From these results, it is suggested that antidementia effect of SSB is due to its neuroprotective effect against $A{\beta}$ (25-35)-induced neurotoxicity and that SSB may have a therapeutic role in preventing the progression of Alzheimer's disease.

• Journal of Sasang Constitutional Medicine
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• v.21 no.3
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• pp.138-153
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• 2009

1. Objectives: Yeolda-Hanso tang (YH) has long been used as traditional herbal formula in Korea as various diseases. Now we modified Yeolda-Hanso tang (YH) for neurodegenerative diseases treatment and named New-Yeolda-Hanso tang (NYH). We investigated neuroprotective effects of NYH on NGF-differentiated PC12 cells cytotoxicity induced by $\beta$-Amyloid peptide (A$\beta$25-35) and evaluated the ability of NYH to prevent and treat for neurodegenerative diseases via autophagy enhancement. 2. Methods and Results: 1) Protective effect of NYH on PC12 cells cytotoxity induced by A$\beta$25-35. PC12 cells survival was measured by MTT and lactate dehydrogenase (LDH) assay. $20{\mu}M$ $\beta$-Amyloid peptide (A$\beta$25-35) induced cytotoxicity on NGF-differentiated PC12 cells. NYH attenuated the cytotoxic effects of A$\beta$25-35 in a dose-dependent manner. 2) Pharmacological induction of Autophagy by NYH in PC12 cells Autophagy induction and activation was measured by immunoblot assay. Marker of autophagy, LC3 II expression and the ratio of LC3-II/I was slightly increased in the protein treated with YH, and significantly augmented in the protein treated with NYH. NYH-induced increase of LC3-II protein level was inhibited by 3MA. 3) Induction of Autophagy by NYH on A$\beta$25-35-induced injury in PC12 cells In MTT assay, $100{\mu}g/ml$ re-treated NYH attenuated $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. Protection effect of NYH was blocked by autophagy inhibitor 3MA. In immunoblot assay, $1200{\mu}g/ml$ pre-treated NYH activated autophagy in $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. The observed effect was partially blocked by 3MA. 3. Conclusions: All the results indicated that NYH possesses neuroprotective potential partially mediated by autophagy enhancement and NYH may be considered to be a promising new herbal formula to prevent and treat for neurodegenerative diseases including Alzheimer's disease (AD).

• Journal of Oriental Neuropsychiatry
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• v.24 no.3
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• pp.309-320
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• 2013

Objectives : There is a possibility LRE as remedy in Alzheimer disease (AD), but it's nerve protection effect and mechanism have to be elucidate. In this research, we applied LRE on $A{\beta}_{25-35}$ pre-treated SH-SY5Y cells, to find out the nerve protection effect and mechanism in AD cell model. Methods : We tried to confirm that effect by experimenting with 20, 50, and $100{\mu}g/ml$ concentration of LRE as a medicine. Next experiment, we assessed damage effect which induced $A{\beta}_{25-35}$, known to cause AD, on SH-SY5Y cell. In addition, cellular viability test is executed under $H_2O_2$ treatment condition in a SH-SY5Y cell. Results : 1. In $A{\beta}_{25-35}$ treated SH-SY5Y cell, LRE exhibited an anti-phosphorylation effect about tau protein, JNK, and IKB. 2. LRE prevent nerve cell apoptosis, which indued $A{\beta}_{25-35}$ and oxidative stress, modify JNK engaged synaptic structure and $NF{\kappa}B$ induced p75-neurotrophin receptor polymorphism. Conclusions : We found that LRE prevented oxidative stress-induced cellular destruction, for example, increased SOD activity of $A{\beta}_{25-35}$ treated SH-SY5Y cell and reduced toxicity of oxygen free radical. Consequently, the ingredients of LRE have a role as a catalyzer for $A{\beta}_{25-35}$ clearance and as scavenger for active oxygen free radical.

• Journal of Life Science
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• v.29 no.2
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• pp.173-180
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• 2019

Amyloid ${\beta}$-protein ($A{\beta}$) is the principal component of senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors, including antioxidants and proteoglycans, modify $A{\beta}$ toxicity. It is worthwhile to isolate novel natural compounds that could prove therapeutic for patients with AD without causing detrimental side effects. In this study, we investigated the in vitro neuroprotective effects of the ethyl acetate fraction of methanol extract of Ophiophogon japonicas (OJEA fraction). We used an MTT reduction assay to detect protective effects of the OJEA fraction on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used a cell-based ${\beta}$-secretase assay system to investigate the inhibitory effect of the OJEA fraction on ${\beta}$-secretase activity. In addition, we performed an in vitro lipid peroxidation assay to evaluate the protective effect of the OJEA fraction against oxidative stress induced by $A{\beta}_{25-35}$ in PC12 cells. The OJEA fraction had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and was strongly inhibitory to ${\beta}$-secretase activity, which resulted in the attenuation of $A{\beta}$ generation. In addition, the OJEA fraction significantly decreased malondialdehyde (MDA) content, which is induced by the exposure of PC12 cells to $A{\beta}_{25-35}$. Our results suggested that the OJEA fraction contained active compounds exhibiting a neuroprotective effect on $A{\beta}$ toxicity.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.331-339
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• 2001

목적 : 본 연구는 식풍해경(熄風解痙), 소산풍열(疏散風熱) 효능이 있는 백강잠이 치매에 미치는 영향을 알아보기 위하여 실험을 행하였다. 방법 : 치매 유발물질인 $amyloid{\beta}(A{\beta})$ 25-35를 흰쥐의 뇌 astrocyte에 처리한 후 대표적인 항산화 효소인 catalase, superoxide dismutase,glutathione peroxidase 및 glutathione-S-transferase의 활성 변화와 NO 생성 변화를 관찰하였다. 결과 $A{\beta}$ 25-35 처리로 catalase와 superoxide dismutase 활성이 현저히 감소하였으나 백강잠을 처리한 경우는 이들 효소 활성이 크게 증가하였다. 그리고, $A{\beta}$ 25-35의 농도에 의존적으로 증가된 NO 생성은 백강잠의 농도에 의존적으로 유의성 있게 억제되는 것으로 나타났다. 결론 : 백강잠은 항산화계 효소의 활성화 및 $A{\beta}$처리와 같은 치매유발 물질의 독성에 대한 적응능력 향상을 통하여 astrocyte를 보호하는 효능을 가지는 것으로 사료되며, 아울러 노인성 치매 등 임상적 응용에 그 효과가 기대된다.

• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.235-241
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• 2000

호도(胡桃)(Juglandis semen)가 치매에 미치는 영향을 알아보기 위하여 치매(Alzheimer's disease) 유발물질로 알려진 amyloid-{$\beta}(A{\beta})$ 25-35를 흰쥐의 뇌 신경세포의 일종인 astrocyte에 처리한 후 뇌의 신경세포에 대한 독성 및 세포막에서의 지질 과산화에 미치는 영향을 검토하였다. 호도(胡桃)는 $A{\beta})$ 25-35로 인한 신경세포의 파괴를 억제하는 것으로 나타나 신경세포의 손상을 예방하고 보호하는 효과가 있었다. 그리고, 지질의 과산화 지표인 malondialdehyde 생성은 $A{\beta})$ 25-35 처리로 크게 증가하였으나, 호도(胡桃)의 전처리와 후처리로 크게 감소되어 호도(胡桃)가 세포막 파괴로 인한 뇌세포의 손상을 방지하는 것으로 나타났다. 이러한 결과들을 볼 때, 호도(胡桃)는 신경세포의 하나인 astrocyte에 대한 보호효과와 세포막에서 지질의 과산화를 저해 및 $A{\beta})$ 25-35 처리와 같은 치매 유발 독성에 대한 적응능력 향상을 통하여 뇌 신경세포를 보호하는 효과가 있음을 보여주는 것으로 노인성 치매 등의 임상적 응용에 그 효과가 기대된다.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.79-86
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• 2013

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against ${\beta}$-amyloid ($A{\beta}_{25-35}$)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against $A{\beta}_{25-35}$-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated $A{\beta}_{25-35}$-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, $A{\beta}_{25-35}$-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of ${\gamma}$-glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against $A{\beta}_{25-35}$-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer's disease.

• Nutrition Research and Practice
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• v.9 no.5
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• pp.480-488
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• 2015

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide ($A{\beta}$) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS: Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an $A{\beta}_{25-35}$-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress. RESULTS: In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the $A{\beta}_{25-35}$-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the $A{\beta}_{25-35}$-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day. CONCLUSIONS: The present results suggest that CA improves $A{\beta}_{25-35}$-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.

• YAKHAK HOEJI
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• v.46 no.3
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• pp.185-191
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• 2002

Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory. Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well-known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDA), $\beta$-amyloid fragment ( $A_{{beta}25-35)}$), and various oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by glutamate. However, tacrine inhibited the toxicity induced by NMDA in a concentration-dependent fashion. In addition, tacrine significantly inhibited the $A_{{beta}25-35)}$-induced neuronal injury at the concentration of 50 $\mu$M. In contrast, donepezil did not reduce the NMDA- nor $A_{{beta}25-35)}$-induced neuronal injury. Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity, the neuroprotective effects by tacrine against the NMDA- and $A_{{beta}25-35)$-induced toxicity may be beneficial for the treatment of AD. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.