• Korean Journal of Pharmacognosy
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• v.41 no.3
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• pp.166-173
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• 2010

Oxidative stress to proteins, lipids, or DNA is higher in human autopsy tissue and in rodent models of a number of neurodegenerative conditions, including Alzheimer's and Parkinson's disease. On the basis of this information, we established a screening system using N18-RE-105 cells to identify therapeutic agents that can protect cells from glutamate toxicity. During the course of our screening program, we recently isolated the active compound 9-hydroxy-$\alpha$-tocopherone ($\alpha$-TP), which prevents glutamate-induced cell death, from Viola mandshurica. The chemical structure of $\alpha$-TP was identified using spectroscopic methods and by comparison with literature values. Antioxidant activity and protective effects of $\alpha$-TP were evaluated by DPPH radical-scavenging assay, morphological assay, MTT reduction assay, and lactate dehydrogenase (LDH) release assay. These results suggest that $\alpha$-TP could be a new potential chemotherapeutic agent against neuronal diseases.

• 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.

• Bulletin of the Korean Chemical Society
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• v.32 no.12
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• pp.4309-4315
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• 2011

For synthesis of benzastatin E, F and G analogues, the indole-2-carbaldehydes with or without substituents at C-5 position were prepared as key intermediates. Several synthetic attempts to achieve benzastatin E-G analogues were suggested using the indole-2-carbaldehyde intermediates.

• Macromolecular Research
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• v.14 no.3
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• pp.387-393
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• 2006

Nanoparticles of Poly(L-glutamic acid) (PG) conjugated to the anticancer drug paclitaxel and targeted moiety folic acid (FA) were synthesized and characterized in vitro. The nanoparticles were designed to take advantage of FA targeting to folate receptor (FR) positive cancer cells. The chemical composition of the conjugate was characterized by $^1H-NMR$, FTIR and UV/vis spectroscopy. The selective cytotoxicity of the FA-PG-paclitaxel conjugates was evaluated in FR positive cancer cells. The interaction of the conjugate was visualized by fluorescence microscopy with results confirming the successful preparation of the conjugate and the production of nanoparticles of about 200-300 nm in diameter. The amount of paclitaxel conjugated to FA-PG was 25% by weight. Cellular uptake of the conjugate was FA dependent, and the conjugate uptake was mediated specifically by the folate receptor. These results demonstrate the improved selective toxicity and effective delivery of an anticancer drug into FR bearing cells in vitro.

• 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.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.531-544
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• 2002

Ginseng is the best known and most popular herbal medicine used worldwide. Ameliorating effects of ginseng were observed on the models of scopolamine-induced, aged or hippocampal lesioned learning and memory deficits. Further beneficial effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. In spite of these beneficial effects of ginseng on the CNS, little scientific evidence shows at the cellular level. In the present study, we have employed cultures of rat hippocampal neurons and examined the direct modulation of ginseng on NMDA receptor-induced changes in $[Ca^{2+}]_i$ and -gated currents using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques, respectively. We found that ginseng total saponins inhibited NMDA-induced but less effectively glutamate-induced increase in $[Ca^{2+}]_i$ Ginseng total saponins also modulated $Ca^{2+}$ transients evoked by depolarization with 50 mM KCI along with its own effects on $[Ca^{2+}]_i$. Among ginsenosides tested, ginsenoside $Rg_3$ was found to be the most potent component for ginseng actions on NMDA receptors. Furthermore, we examined the inhibitory effects ofbiotransformants of ginsenosides on NMDA receptor using purified stereoisomers of ginsenosides. 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_3$, produced the strongest inhibition while 20(S)-ginsenoside $Rh_1$ and Compound K produced the moderate inhibition on NMDA-induced increase in $[Ca^{2+}]_i$. The data obtained suggest that the inhibition of NMDA receptors by ginseng, in particular by 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_2$, could be one of mechanisms for ginsengmediated neuroprotective actions.

• Toxicological Research
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• v.17
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• pp.135-138
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• 2001

Female Wistar rats were randomly divided into 5 groups: Control, received distilled water; Low lead, received 0.5 g/ιlead (as acetate) in drinking water; High lead, received 2.0 g/ιlead; Low lead + Minerals, received 0.5 g/ιlead in drinking water and received minerals (Ca$^{2+}$, 25 mg/kg/day; Fe$^{3+}$, 0.47 mg/ kg/day; Zn$^{2+}$, 0.33 mg/kg/day; Se, 0.83 $\mu\textrm{g}$/kg/day) by gavage; High lead + Minerals, received 2.0 g/ιlead and received the same minerals. Animals exposure to lead was from 10 days before mating till postnatal day 21; and the minerals was administered from the first day of pregnancy and during lactation. No statistical difference was found either in body weights or in blood lead levels between the pups received minerals and those only exposed to lead at the same dose. The developmental and behavioral teratological effects of lead on pups, such as time-lag of eye opening, pinna detachment, fur developing, incisor eruption, ear unfolding, and surface righting were observed in this study; and the minerals decreased the toxicity of lead either in low or in high lead exposure pups. The numbers of step-down were significantly increased in lead exposed animals, and the effect of intervention by the minerals was appeared only in the pups exposed to low lead. The ChAT activity and levels of glutamate and aspartate in hippocampus decreased in treated animals compared to control animals, no effect of intervention by the minerals was found. The results of this study indicate that the applied multi-minerals can alter the outcome of develop-mental lead poisoning in rats.s.s.s.

• BMB Reports
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• v.40 no.6
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Korean Journal of Plant Resources
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• v.13 no.3
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• pp.171-178
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• 2000

This study was performed to investigate the possible effects of some plants protecting intact rat liver damaged by $CCl_4$. The extract of mugwort (Artemsiae capillaris), soybean sprout and pine leaf (Pinus strobus) inhibited markedly the in vitro activities of rat liver fatty acid synthase, whereas those of shiitake (Lentinus ododes), Houttuynia cortata, Acanthopanacis cortex and buckwheat leaves had less effects. Treatment with the water extract of pine leaf and soybean sprout caused a marked decrease in the $CCl_4$-induced toxicity in rat liver, judged from their effects on the levels of glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase(GPT) in the serum. The extract of mugwort and soybean sprout reduced markedly the content of liver microsomal peroxides induced by $CCl_4$ treatment and serum TBA values, respectively. The extract of soybean sprout decreased efficiently the content of liver triglyceride elevated by $CCl_4$ treatment. Nevertheless, the extracts did not exert the supression of hepaticmegaly induced by $CCl_4$. The results suggest that soybean sprout and pine leaf may be potential sources improved the biochemical parameters like as peroxidation value or serum GOT and GPT, although these extracts had minimal effects in the increase of liver size induced by carbon tetrachloride.

• CELLMED
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• v.9 no.1
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• pp.2.1-2.6
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• 2019

Decoction of Cocos nucifera husk fibre is used indigenously in Nigeria for malaria treatment. Polyphenols have been identified as the phytochemicals responsible for the antimalarial activity of Cocos nucifera husk fibre, though their toxicity has not been evaluated. The polyphenols of Cocos nucifera husk fibre were therefore evaluated for their effects on selected kidney function indices in mice. Fifty mice were randomly divided into five groups (A-E) of ten mice each. Mice in group A were orally administered 5% DMSO solution while those in groups B, C, D and E were orally administered 31.25, 62.5, 125 and 250 mg/Kg body weight of the polyphenols respectively for seven days. Serum urea, creatinine and uric acid concentrations were determined. Serum levels of sodium, potassium, chloride and calcium ions and kidney alkaline phosphatase (ALP), glutamate dehydrogenase (GDH) and gamma-glutamyltransferase (GGT) activities were also determined. The results showed that the polyphenols significantly reduced (p<0.05) urea concentration at 250 mg/Kg body weight and creatinine concentration at all doses compared to controls. The polyphenols caused no significant alteration (p>0.05) in serum uric acid concentration and kidney ALP, GGT and GDH activities compared to controls. There was significant increase (p<0.05) in serum sodium ion concentration at 31.25, 125 and 250 mg/Kg body weight of polyphenols whereas significant increase (p<0.05) in serum potassium and chloride ions was observed at 62.5 and 250 mg/Kg body weight compared to controls. Thus, polyphenols of Cocos nucifera husk fibre may adversely affect some osmoregulatory functions of the kidney, especially at higher concentrations.