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.

This study was pcrformed to evaluate the antioxidant activity of silymarin against human low density lipoproteins(LDL) oxidation. Silymarin extracted from Silybum marianum was successively purified with solvent fractionation and followed by silica gel column chromatography. The active substances were separated by HPLC and the isolated active substances, silymarin were identified by IR, NMR, GC-MS as silymarin. Silymarin inhibited at the 5 uM Cu^(2+)-mediated oxidation of human low density lipoprotein (LDL) in a dose dependent manner. Silymarin completely inhibited LDL oxidation at 50 ug/ml concentration. These findings suggest that silymarin may protect LDL against oxidation in atherosclerotic lessions.

Background : Alzheimer`s disease (AD) is characterized by neuronal loss and extracellular senile plaque, whose major constituent is β-amyloid (Aβ), a 39-43 amino acid peptide derived from amyloid precursor protein. In cultures, Aβ can directly induce neuronal cell death and can render neurons vulnerable to excitotoxicity which may involve glutamate release and N-methyl-D-aspartate (NMDA) receptor. Silybum marianum (SM) has been used for centuries to treat liver disease due to its antioxidant, and anti-inflammatory properties. In particular, Silymarin, an active constituent of SM, has been reported to decrease lipid peroxidation. Therefore we hypothesized that SM might protect neurons against neurodegeneration in AD due to its antioxidant and anti-inflammatory activities. In the present study, the protective effect of ethanol extract from the stem of SM on Aβ (25-35)-induced neuronal cell death was examined in primary cultured rat cortical neurons. Methods and Results : Primary cultured cortical neurons were prepared using embryonic day 15 SD rat fetuses. Neurotoxicity experiments were performed on cultured neurons after 4-5 days in vitro. The cells were treated with 10 μM Aβ (25-35) or 1 mM NMDA for 36 h or 14 h, respectively. SM was applied 15 min before treatment of Aβ (25-35) or NMDA and also present in the medium during the incubations. The viability of neurons was monitored using a colorimetric MTT assay and Hoechst 33342 staining. The expression levels of anti-apoptotic and pro-apoptotic proteins were detected by western blot. An Ethanol extract of the stem of SM (10 and 50 μg/ml) significantly prevented Aβ (25-35)-induced apoptotic neuronal cell death in cultured cortical neurons. Furthermore SM inhibited Aβ (25-35)-induced decrease of anti-apoptotic protein, Bcl-2, and increase of pro-apoptotic proteins, Bax and active caspase-2, in western blot analysis. SM (10 and 50 μg/ml) also reduced NMDA-induced neuronal cell death. These results suggest that NMDA glutamate receptor activation is implicated in Aβ (25-35) -induced neuronal apoptotic death. Conclusion : The present study suggests that SM has a possible therapeutic role for preventing the progression of neurodegenerative disease such as Alzheimer's disease.