• Proceedings of the PSK Conference
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• 2002.10a
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• pp.228.2-229
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• 2002

Methylmercury (MeHg). a potent neurotoxicant. produces neuronal death that may be partially mediated by glutamate. Glutamine synthetase (GS), a glial-specific enzyme. catalyzes the synthesis of glutamine from glutamate and ammonia and is associated with ischemic injury and neurological diseases. Objectives of this experiment are to investigate whether in vivo and in vitro MeHg exposure have adverse effects on GS and whether duration of exposure to MeHg and glutamate co-treatment playa role in MeHg-induced toxicity. (omitted)

• Natural Product Sciences
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• v.11 no.3
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• pp.179-182
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• 2005

We investigated that water extract of Acanthopanax sessiliflorus roots rescued the N-methyl-D-aspartate (NMDA), agonist of glutamate receptor, -induced toxicity in rat organotypic hippocampal slice culture. When the cell death in NMDA only-treated hippocampal slices was set 100%, A. sessiliflorus decreased the cell death to 75.4, 51.6, 48.9, and 40.6% at 1, 10, 50, and $100\;{\mu}g/ml$ treatment, respectively. On the basis of these results, the water extract of A. sessiliflorus roots may be a preventive agent against NMDA-induced cytotoxicity.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.699-706
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• 2006

The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. Both hesperidin and hesperetin exhibited similar patterns of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. While hesperidin was inactive, hesperetin was found to be a potent antioxidant, inhibiting lipid peroxidation initiated in rat brain homogenates by $Fe^{2+}$ and L-ascorbic acid. In consistence with these findings, hesperetin protected primary cultured cortical cells against the oxidative neuronal damage induced by $H_2O_2$ or xanthine and xanthine oxidase. In addition, it was shown to attenuate the excitotoxic neuronal damage induced by excess glutamate in the cortical cultures. When the excitotoxicity was induced by the glutamate receptor subtype-selective ligands, only the N-methyl-D-aspartic acid-induced toxicity was selectively and markedly inhibited by hesperetin. Furthermore, hesperetin protected cultured cells against the $A_{{\beta}(25-35)}-induced$ neuronal damage. Hesperidin, however, exerted minimal or no protective effects on the neuronal damage tested in this study. Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases.

• CELLMED
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• v.4 no.3
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• pp.18.1-18.5
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• 2014

Leea asiatica (L.) Ridsdale, a folk medicinal plant is used by the ethnic people of North East India for the treatment of hepatic disorder. In this study, we have investigated the hepatoprotective and antioxidant activity of L. asiatica leaves against acetaminophen induced hepatotoxicity. Methanol extract of L. asiatica (150 and 300 mg/kg/day, p.o.) were administered to rats for three consecutive days followed by single acetaminophen (3000 mg/kg, p.o.) administration on $3^{rd}$ day. After 48 h of acetaminophen administration animals were sacrificed and biochemical estimation of serum, in vivo antioxidant activity using liver tissue were carried out. High levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol and triglycerides were observed in disease control group, which found near to normal in extract treated groups. Higher dose exhibited significant hepatoprotective activity against acetaminophen induced toxicity. Level of superoxide dismutase, catalase, glutathione peroxidase in liver tissue, and reduced glutathione in liver and blood were also significantly increased in extract (300 mg/kg) treated animals compare to disease control group. In this study we found that leaves of L. asiatica exhibited potent hepatoprotective activity against acetaminophen induced hepatic damage in experimental animals which justify the folklore claim, and the possible mechanism of this activity may be due to strong antioxidant activities of extract.

• 한국약용작물학회:학술대회논문집
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• 2007.05a
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• pp.213-214
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• 2007

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.195.2-195.2
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• 2003

The CH$_2$Cl$_2$ fraction of the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae) significantly protected primary cultures of rat cortical cells exposed to the excitotoxic amino acid, L-glutamate. Several lignans including (-)-isoguaiacin, meso- dihydroguaiaretic acid, machilin A, (+)-galbelgin, licarin A, (-)-sesamin, and (+)-guaiacin were isolated from the CH$_2$Cl$_2$ fraction using by bioactivity-guided isolation techniques. Among these lignans, (-)-isoguaiacin, meso-dihydroguaiaretic acid, licarin A and (+)-guaiacin had significant neuroprotective activities against glutamate-induced toxicity in primary cultures of rat cortical cells at concentration ranging from 0.1 ${\mu}$M to 10.0 ${\mu}$M. (omitted)

• YAKHAK HOEJI
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• v.44 no.1
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• pp.29-35
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• 2000

The methanol extracts were prepared from 46 oriental medicines currently used for stroke treatment, and the effects were assessed on the excitotoxic neuronal cell death induced by L-glutamate(Glu) in primary cultured rat cortical neurons. The extracts from Angelicae gigantis Radix, Manitis Squama, Acori graminei Rhizoma, Uncariae Ramulus et Uncus, Alpiniae Fructus, Paeoniae Radix, and Cnidii Rhizoma inhibited the Glu-induced neurotoxicity with the IC$_50$ values of 95.2, 218.6, 263.3, 295.1, 297.9, 310.1, and 446.7 $\mu$g/ m$\ell$, respectively. The extracts from Arisaematis Rhizoma, Loranthi Ramulus, Anemarrhenae Rhizoma, Carthami Flos, Clematidis Radix, Bambusae Concretio Silicea, and Angelicae koreanae Radix also exhibited significant inhibition of the toxicity. In contrast, the extracts from Aconiti Tuber Araliae cordatae Radix, Curcumae Rhizoma, Leonuri Herba, Polygalae Radix, Salviae Radix, and Siegesbeckiae Herba increased the Glu-induced toxicity at the concentrations of 500 and 1000 $\mu$g/m$\ell$. Rest of the extracts evaluated in the present study showed minor or negligible inhibition. liken together the oriental medicines including Angelicae gigantis Radix, Muitis Squama, Acori graminei Rhizoma, Uncariae Ramulus et Uncus, and Alpiniae Fructus appear to exert pharmacological effects through the inhibition of excitotoxic neuronal cell death. Further studies are in progress to characterize active principles in these extracts.

• Natural Product Sciences
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• v.9 no.2
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• pp.83-86
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• 2003

In the present study, Thespesia populnea (Malvaceae) bark was extracted with methanol and water. The extracts were vacuum dried to yield the respective methanol (MET) and aqueous extract (AET). The extracts were evaluated for hepatoprotective activity against carbon tetrachloride $(CCl_{4})$ induced liver damage at 2 dose levels (250 and 500 mg/kg). The biochemical parameters observed in serum were total bilirubin, alkaline phosphatase (ALP), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and total protein. Aspartate transaminase (AST), alanine transaminase (ALT) and total protein levels in liver were also evaluated. Histopathological study on the liver tissue was also performed. The extracts exhibited dose dependent reduction in total bilirubin, ALP SGOT, SGPT, AST, ALT and increase in total protein (serum and liver) levels. The extracts also exhibited only mild hepatocytic damage compared to the $CCl_{4}$ Treated group. MET was found to exhibit higher hepatoprotection than AET.

• Korean Journal of Pharmacognosy
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• v.45 no.3
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• pp.214-219
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• 2014

Artemisia apiacea is a traditional herbal medicine using treatment of eczema and jaundice in Eastern Asia including China, Korea, and Japan. In this study, the three phytosterol constituents were isolated and identified from the hexane fraction of 80% aqueous methanol extract of A. apiacea. Compounds were isolated using open column chromatography (silica gel). Their chemical structures were also established using $^1H$-NMR and $^{13}C$-NMR. Moreover, neuroprotective activity of each compound against glutamate-induced neurotoxicity in hippocampal HT-22 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, Inhibition of reactive oxygen species (ROS) and calcium ion ($Ca^{2+}$) accumulation were measured for elucidation of neuroprotective mechanism of isolated compounds. They showed that stigmasterol had neuroprotective activity against the glutamate-induced toxicity by inhibition of ROS and $Ca^{2+}$ production. In conclusion, isolated compound of A. apiacea might be useful for therapeutic agent against neurodegenerative diseases.

• YAKHAK HOEJI
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• v.49 no.1
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• pp.30-37
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• 2005

Xuesaitong Ruanjiaonang (XR), a soft capsule containing Panax notoginseng saponins as main ingredients, is believed to remove extravasated blood and increase cerebral blood flow by improving blood circulation, and therefore, has been used in China to treat ischemic stroke or hemiplegia caused by cerebral thrombosis. To characterize pharmacological actions of XR, the present study evaluated its effects on neuronal cell damage induced by various oxidative insults or excitotoxic amino acids in primary cultured rat cortical cells. The neuronal cell viability was not affected by XR with the exposure for 2 h at the concentrations tested in this study ($10{\sim}1000\;{\mu}g/ml$). However, significant reduction of the cell viability was observed when the cultured cells were exposed to XR at $1000\;{\mu}g/ml$ for 24 h. XR was found to concentration-dependently inhibit the oxidative neuronal damage induced by $H_{2}O_2$, xanthine/xanthine oxidase or $Fe^{2+}$/ascorbic acid. In addition, it dramatically inhibited the excitotoxic damage induced by glutamate or N-methyl-D-aspartate (NMDA). We found that the NMDA-induced neurotoxicity was inhibited more effectively and potently than the glutamate-induced toxicity. Moreover, XR was found to exert mild inhibition of lipid peroxidation induced by $Fe^{2+}$/ascorbic acid in rat brain homogenates and some 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate neuroprotective and antioxidant effects of XR, showing inhibition of oxidative and excitotoxic damage in the cultured cortical neurons, as well as inhibition of lipid peroxidation and its radical scavenging activity. Considering that excitotoxicity and oxidative stress pl ay crucial roles in neuronal cell damage during ischemia and reperfusion, these results may provide pharmacological basis for its clinical usage to treat ischemic stroke.