Alzheimer’s disease (AD), a progressive neurodegenerative disorder that deprives the patient of memory, is associated mainly with extracellular senile plaque induced by the accumulation of amyloid β protein (Aβ). Silybum marianum (Asteraceae; SM) is a medicinal plant that has long been used in traditional medicine as a hepatoprotective remedy owing to its antioxidant and anti-inflammatory activities. The present study examined the methanol extract of the aerial parts of SM for neuroprotection against Aβ (25-35)-induced neuronal death in cultured rat cortical neurons to investigate a possible therapeutic role of SM in AD. The primary cortical neuron cultures were prepared using embryonic day 15 to 16 SD rat fetuses. Cultured cortical neurons exposed to 10 μM Aβ (25-35) for 36 h underwent neuronal cell death. At 10 and 50 μg/mL, SM prevented Aβ (25-35)-induced neuronal cell death and apoptosis in cultured cortical neurons. Furthermore, SM inhibited the Aβ (25-35)-induced decrease in anti-apoptotic protein, Bcl-2, and the increase in the proapoptotic proteins, Bax and active caspase-3. Cultured cortical neurons exposed to 1 mM N-methyl-D-aspartate (NMDA) for 14 h induced neuronal cell death. SM (10 and 50 μg/mL) prevented NMDA-induced neuronal cell death. These results suggest that SM inhibited Aβ (25-35)-induced neuronal apoptotic death via inhibition of NMDA receptor activation and that SM has a possible therapeutic role in preventing the progression of neurodegeneration in AD.

Background : Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss, cognitive impairment and personality defects accompanied by diffuse structural abnormalities in the brain. The major pathological hallmarks of AD include beta amyloid (Aß) protein deposition, presence of neurofibrillary tangles and neurodegeneration of cholinergic neurons. Aß, a 39-43 amino acid proteolytic fragment of amyloid precursor protein, is the major constituent of the senile plaques. Rice bran, the major byproduct of the rice milling industry, is the source of a high quality vegetable oil. Rice bran oil (RBO) has attracted much medicinal attention for its strong hypocholesterolemic properties because of its balanced fatty acid composition and high levels of antioxidant phytochemicals such as oryzanols, tocopherols and tocotrienols. The present study aims to investigate the protective effect of RBO against Aß (25-35)-induced neurotoxicity in in vitro and in vivo. Methods and Results : Memory impairment was produced by intracerebroventricular (i.c.v) microinjection of 15 nmol Aß (25-35) and measured by passive avoidance test in ICR mice. Glutathione concentration, lipid peroxidation rate and acetylcholine esterase activity were measured in mice brain. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), inflammatory factors, and anti-apoptotic and pro-apoptotic proteins in mice brains were detected by Western blot. Cerebral cortical neuronal cells were cultured from 15-days-old fetus. Cortical neurons were incubated with 10 μM Aß (25-35) for 36 h. Cell viability was measured by MTT assay. Chronic treatments of RBO (0.1-1 ml/kg, 8 days, p.o.) protected against memory impairment induced by Aß (25-35). Depletion of glutathione level, lipid peroxidation and increased acetylcholine esterase activity by the treatment with Aß (25-35) were inhibited by administration of RBO. The increase of phosphorylated MAPKs, inflammatory factors, and proapoptotic proteins and the decrease of antiapoptotic protein in Aß (25-35)-administered mice brain were significantly inhibited by treatment with RBO. RBO (0.1-5ul/ml) inhibited 10μM Aß (25-35)-induced neuronal cell death in cultured cortical neurons. Conclusion : The present study suggests the role of RBO as a promising therapeutic for neurodegenerative diseases like AD and stroke.

The present study investigated an ethanol extract (SSB) of a mixture of three medicinal plants of Vitisamurensis, Aralia cordata, and Glycyrrhizae radix for possible neuroprotective effects on neurotoxicity induced byAmyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cor-tical neurons to 15μM Aβ (25-35) for 36h induced neuronal apoptotic death. At 1-30㎍/㎖, SSB inhibited neuronal death,elevation of intracellular calcium concentration ([Ca²+]i), and generation of reactive oxygen species (ROS) induced by Aβ(25-35) in cultured cortical neurons. Memory impairment and increase of acetylcholinesterase activity induced by intra-cerebroventricular injection of mice with 16nmol Aβ (25-35) was inhibited by chronic treatment with SSB (25, 50 and100㎎/㎏, p.o., for 8 days). From these results, it is suggested that antidementia effect of SSB is due to its neuroprotectiveeffect against Aβ (25-35)-induced neurotoxicity and that SSB may have a therapeutic role in preventing the progression ofAlzheimer’s disease.

The present study investigated an ethanol extract of Chaenomeles sinensis fruit (CSF) for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10μM Aβ (25-35) for 36 h induced neuronal apoptotic death. At 0.1-10μg/ml, CSF inhibited neuronal death, elevation of intracellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) induced by Aβ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of mice with 15 nmol Aβ (25-35) was inhibited by chronic treatment with CSF (10, 25 and 50 mg/kg, p.o. for 7 days) as measured by a passive avoidance test. CSF (50 mg/kg) inhibited the increase of cholinesterase activity in Aβ (25-35)-injected mice brain. From these results, we suggest that the antidementia effect of CSF is due to its neuroprotective effect against Aβ (25-35)-induced neurotoxicity and that CSF may have a therapeutic role for preventing the progression of Alzheimer's disease.

The present study investigated an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcumalongae radix, Phellinus linteus, and Scutellariae radix for possible neuroprotective effects on neurotoxicity induced by amyloid βprotein (Aβ) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to10µM Aβ (25-35) for 36h induced neuronal apoptotic death. At 1-50㎍/㎖, HS0608 inhibited neuronal death, elevation of intra-cellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) induced by Aβ (25-35) in primary cul-tures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Aβ (25-35) wasinhibited by chronic treatment with HS0608 (25, 50 and 100㎎/㎏, p.o. for 7 days) as measured by a passive avoidance test. Fromthese results, we suggest that the antidementia effect of HS0608 is due to its neuroprotective effect against Aβ (25-35)-inducedneurotoxicity and that HS0608 may have a therapeutic role in preventing the progression of Alzheimer’s disease.

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has pharmacological effects such as anti-inflammatory, antiallergic, analgesic and antioxidant activities. We investigated a methanol extract of Moutan cortex for neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to 10 μM Aβ (25-35) for 24 h induced neuronal apoptotic death. Moutan cortex inhibited 10 μM Aβ (25-35)-induced neuronal cell death at 30 and 50 μg/ml, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Moutan cortex inhibited 10 μM Aβ (25-35)-induced elevation of intracellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) which were measured by fluorescent dyes. Moutan cortex also inhibited glutamate release into medium induced by 10 μM Aβ (25-35), which was measured by HPLC. These results suggest that Moutan cortex prevents Aβ (25-35)-induced neuronal cell damage by interfering with the increase of [Ca2+]i, and then inhibiting glutamate release and ROS generation. Moutan cortex may have a therapeutic role in preventing the progression of Alzheimer's disease.

Sanguisorbae radix (SR) from Sanguisorba officinalis L. (Losaceae) is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of SR on amyloid β Protein(25-35) (Aβ (25-35)), a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. SR, over a concentration range of 10-50 μg/ml, inhibited the Aβ (25-35) (10 μM)-induced neuronal cell death, as assessed by a 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. Pretreatment of SR (50 μg/ml) inhibited 10 μM Aβ (25-35)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, fluo-4 AM. SR (10 and 50 μg/ml) inhibited glutamate release into medium induced by 10 μM Aβ(25-35), which was measured by HPLC, and generation of reactive oxygen species. These results suggest that SR prevents Aβ (25-35)-induced neuronal cell damage in vitro.

Caulis Bambusae in Taenia is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of Caulis Bambusae in Taenia (CB) from Phyllostachys nigra Munro var. henonis Stapf (Gramineae) on amyloid β protein (25-35) (Aβ (25-35)), a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. CB, over a concentration range of 10-50μg/μl, inhibited the Aβ (25-35) (10 μM)-induced neuronal cell death, as assessed by a 3-[4,5-dimethyIthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. CB (50 μg/μl) inhibited glutamate release into medium induced by 10 μM Aβ, (25-35) which was measured by HPLC. Pretreatment of CB (50 μg/μl) inhibited 10μM Aβ (25-35)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, fluo-4 AM, and generation of reactive oxygen species. These results suggest that CB prevents Aβ (25-35)-induced neuronal ell damage in vitro.