Aralia cordata protects against amyloid beta protein (25-35)-induced neurotoxicity in cultured neurons and has antidementia activities in mice.

The present study investigated an ethanol extract of the aerial part of Aralia cordata Thunb. (Araliaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid beta (Abeta) protein (25 - 35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to 10 muM Abeta(25 - 35) for 36 h induced neuronal apoptotic death. At 1 - 10 mug/ml, A. cordata inhibited neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), glutamate release into the medium, and generation of reactive oxygen species (ROS) induced by Abeta(25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Abeta(25-35) was inhibited by chronic treatment with A. cordata (50 and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test, and corresponding reductions were observed in brain cholinesterase activity and neuronal death measured histologically in the hippocampal region. Oleanolic acid isolated from A. cordata also inhibited neuronal death, elevation of [Ca(2+)](i), glutamate release, and generation of ROS induced by Abeta(25-35) in cultured rat cortical neurons, suggesting that the neuroprotective effect of A. cordata may be, at least in part, attributable to this compound. From these results, we suggest that the antidementia effect of A. cordata is due to its neuroprotective effect against Abeta(25-35)-induced neurotoxicity and that A. cordata may have a therapeutic role in preventing the progression of Alzheimer's disease.

Anti-ischemic activities of aralia cordata and its active component, oleanolic acid.

Aralia has been reported to exhibit various pharmacological properties, including anti-inflammatory, antidiabetic and antioxidant activities. We performed in vitro and in vivo analyses on the neuroprotective effects of an ethanolic extract of the aerial parts of Aralia cordata Thunb. (Araliaceae). In cultured cortical neurons from rats, A. cordata (5-20 microg/mL) inhibited 100 muM hydrogen peroxide (H(2)O(2))-induced apoptotic neuronal death, elevation of intracellular calcium concentration ([Ca(2+)](i)) and generation of reactive oxygen species (ROS). Since oleanolic acid isolated from A. cordata also inhibited H(2)O(2)-induced neuronal death, increase in [Ca(2+)](i) and ROS generation in cultured cortical neurons, some of the neuroprotective effects of A. cordata might be attributable to this compound. In rats, A. cordata prevented cerebral ischemic injury induced by 3 h of middle cerebral artery occlusion, followed by 24 h of reperfusion. Ischemic infarct and edema volumes were significantly reduced in rats that received A. cordata (50 mg/kg, orally). These animals exhibited a corresponding improvement in neurological function and a reduction of neuronal death, as determined histologically from the cortex and hippocampal regions. It is possible that the anti-oxidative properties of A. cordata may be responsible for its neuroprotective effects against focal cerebral ischemic injury. In future, A. cordata might play a therapeutic role in the prevention and treatment of neurodegeneration in stroke.

Neuroprotective effect of Sanguisorbae radix against oxidative stress-induced brain damage: in vitro and in vivo.

Sanguisorbae radix (SR), the root of Sanguisorba officinalis L. (Rosaceae), has been traditionally used for its anti-inflammatory, anti-infectious and analgesic activities in Korea. Previous work has shown that SR prevents neuronal cell damage induced by Abeta (25--35) in cultured rat cortical neurons. The present study was carried out to further investigate the neuroprotective effect of SR on oxidative stress-induced toxicity in primary culture of rat cortical neurons, and on ischemia-induced brain damage in rats. SR, over a concentration range of 10--50 microg/ml, inhibited H2O2 (100 microM)-induced neuronal death, which was significantly inhibited by MK-801 (5 microM), an N-methyl-D-aspartate (NMDA) receptor antagonist, and verapamil (20 microM), an L-type Ca2+ channel blocker. Pretreatment of SR (10-50 microg/ml), MK-801 (5 microM), and verapamil (20 microM) inhibited H2O2-induced elevation of intracellular Ca2+ concentration ([Ca2+]i) measured by a fluorescent dye, Fluo-4 AM. SR (10-50 microg/ml) inhibited H2O2-induced glutamate release into medium measured by HPLC, and generation of reactive oxygen species (ROS) measured by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). In vivo, SR prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct and edema were significantly reduced in rats that received SR (10, 30 mg/kg, orally), with a corresponding improvement in neurological function. Catechin isolated from SR inhibited H2O2-induced neuronal death in cultures. Taken together, these results suggest that SR inhibits H2O2-induced neuronal death by interfering with the increase of [Ca2+]i, and inhibiting glutamate release and generation of ROS, and that the neuroprotective effect of SR against focal cerebral ischemic injury is due to its anti-oxidative effects. Thus SR might have therapeutic roles in neurodegenerative diseases such as stroke.

Neuroprotective effect of Smilacis chinae rhizome on NMDA-induced neurotoxicity in vitro and focal cerebral ischemia in vivo.

Previous work has shown that the Smilacis chinae rhizome (SCR) markedly inhibits amyloid beta protein (25-35)-induced neuronal cell damage in cultured rat cortical neurons. The present study was conducted to further verify the neuroprotective effect of SCR on excitotoxic and cerebral ischemic injury using both in vitro and in vivo studies. Exposure of cultured cortical neurons to 1 mM N-methyl-D-aspartate (NMDA) for 12 h induced neuronal cell death. SCR (10 and 50 microg/ml) inhibited NMDA-induced neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), and generation of reactive oxygen species (ROS) in primary cultures of rat cortical neurons. In vivo, SCR prevented cerebral ischemic injury induced by 3-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct was significantly reduced in rats that received SCR (30 and 50 mg/kg, orally), with a corresponding improvement in neurological function. Moreover, SCR treatment significantly decreased the histological changes observed following ischemia. Oxyresveratrol and resveratrol isolated from SCR also inhibited NMDA-induced neuronal death, increase in [Ca(2+)](i), and ROS generation in cultured cortical neurons, suggesting that the neuroprotective effect of SCR may be attributable to these compounds. Taken together, these results suggest that the neuroprotective effect of SCR against focal cerebral ischemic injury is due to its anti-excitotoxic effects and that SCR may have a therapeutic role in neurodegenerative diseases such as stroke.

Neuroprotective properties of gallic acid from Sanguisorbae radix on amyloid beta protein (25--35)-induced toxicity in cultured rat cortical neurons.

Our previous studies reported that methanol extract of Sanguisorbae radix from Sanguisorba officinalis L. (Rosaceae) prevented neuronal cell damage induced by Abeta (25-35) in vitro. The present study was carried out to investigate the effect of gallic acid isolated from Sanguisorbae radix on Abeta (25-35)-induced neurotoxicity using cultured rat cortical neurons. Gallic acid (0.1, 1 microM) showed a concentration-dependent inhibition on Abeta (25-35) (10 microM)-induced apoptotic neuronal death, as assessed by a 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33,342 staining. Pretreatment of gallic acid inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)) and generation of reactive oxygen species (ROS), which were measured by fluorescent dyes. Gallic acid also inhibited glutamate release into medium induced by 10 microM Abeta (25-35), which was measured by HPLC. These results suggest that gallic acid prevents Abeta (25-35)-induced apoptotic neuronal death by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release and generation of ROS, and that these effects of gallic acid may be partly associated with the neuroprotective effect of Sanguisorbae radix.

3,4-dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid beta protein (25-35)-induced neurotoxicity in cultured rat cortical neurons.

The neuroprotective effect of 3,4-dihydroxybenzoic acid (3,4-DHBA) isolated from Smilacis chinae rhizome against Abeta (25-35)-induced neurotoxicity on cultured rat cortical neurons was found in this study. The protective effect of 3,4-DHBA against Abeta (25-35)-induced neuronal cell death was investigated by measuring cell viability via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. 3,4-DHBA (1 and 10 microM) concentration-dependently inhibited 10 microM Abeta (25-35)-induced neuronal apoptotic death. 3,4-DHBA (1 and 10 microM) inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)), which was measured by a fluorescent dye, Fluo-4 AM. 3,4-DHBA also inhibited glutamate release into medium, reactive oxygen species (ROS) generation, and caspase-3 activation, which were induced by 10 microM Abeta (25-35). These results suggest that 3,4-DHBA prevents Abeta (25-35)-induced neuronal cell damage by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release, generation of ROS and caspase-3 activity.

Protection of amyloid beta protein (25-35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons.

Smilax has various pharmacological effects including antiinflammatory, anticancer and antioxidant activity. The present study aims to investigate the effect of the methanol extract of Smilacis chinae rhizome (SCR) from Smilax china L. (Liliaceae) on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons. Abeta (25-35) (10 microM) produced a reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, an L-type Ca2+ channel blocker, and NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. SCR, over a concentration range of 10-50 microg/ml, inhibited 10 microM Abeta (25-35)-induced neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. SCR (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, Fluo-4 AM. Pretreatment of SCR (10 and 50 microg/ml) also inhibited glutamate release into medium induced by 10 microM Abeta (25-35), which was measured by HPLC, generation of reactive oxygen species and activation of caspase-3. These results suggest that SCR prevents Abeta (25-35)-induced neuronal cell damage in vitro.

Stimulation of 5-HT1A receptor with 8-OH-DPAT inhibits hydrogen peroxide-induced neurotoxicity in cultured rat cortical cells.

We investigated the effect of 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT), a specific 5-HT(1A) receptor agonist, on H(2)O(2)-induced neuronal cell death in cultured rat cortical cells. H(2)O(2) produced a concentration-dependent reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist. Pretreatment of 8-OH-DPAT over the concentration range of 1-100 microM significantly inhibited the H(2)O(2) (100 microM)-induced neuronal cell death as assessed by a MTT assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. The protective effect of 8-OH-DPAT (100 microM) was completely blocked by the simultaneous treatment of 1-(2-methoxyphenyl)-4-[4-(2-phthalimideo)butyl]piperazine (NAN-190, 10muM), a selective 5-HT(1A) receptor antagonist, but not in the presence of the dopamine receptor blocker spiperone (10 microM), indicating that the protective effect of 8-OH-DPAT was mediated via 5-HT(1A) receptors. In addition, 8-OH-DPAT inhibited the H(2)O(2)-induced elevation of glutamate release into the medium and cytosolic Ca(2+) concentration ([Ca(2+)](c)), generation of reactive oxygen species (ROS), and caspase-3 activity. These results suggest that the activation of 5-HT(1A) receptor with 8-OH-DPAT may ameliorate an oxydative stress-induced apoptosis of neuronal cell by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release, generation of ROS and caspase activity.