• Journal of Oriental Neuropsychiatry
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• v.11 no.2
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• pp.11-21
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• 2000

Substance P(SP) can stimulate production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) from astrocytes stimulated with lipopolysaccharide(LPS). The objective of the current study was to determine the effect of Taraxacum officinale(TO) on the production of TNF-${\alpha}$ from primary cultures of rat astrocytes. TO(100& 1000$\mu\textrm{g}$/ml) significantly inhibited the TNF-${\alpha}$ production by astrocytes stimulated with LPS and SP. Interleukin-1(IL-1) has been shown to elevate TNF-${\alpha}$ production from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-${\alpha}$ production from primary astrocytes by TO. Treatment of TO(100 and 1000$\mu\textrm{g}$/ml) to astrocytes stimulated with both LPS and substance P decreased IL-1 production significantly. Moreover, the production of TNF-${\alpha}$ by LPS and substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. These results suggest that TO may inhibit TNF-${\alpha}$ production by inhibiting IL-1 production and that TO has an antiinflammatory activity in the central nervous system.

• Toxicological Research
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• v.8 no.2
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• pp.161-170
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• 1992

The objectives of this sutdy were to investigate the effects of 8-fluorociprofloxacin(8-FCP) on the central nervous system (CNS) and to compare with those of ciprofloxacin(CP). The $LD_{50}$ values of intravenous 8-FCP were similar or slightly lower in rat (M;203.6mg/kg, F;186.1mg/kg)and markedly lower in mice (M;126.5mg/kg, F;163.1mg/kg), as compared to those of CP. However, no recognizable differences in the clinical signs and recovery were found between 8-FCP and CP in both species. In combination with fenbufen, the convulsive liability of 8-FCP was higher than that of CP. At an intravenous dose of 10mg/kg, 8-FCP provoked convulsive signs and subsequent death in mice, whereas CP produced convulsion at a dose of 40mg/kg. The hexobabital -induced sleeping time was markedly lengthened by the oral administration of 8-FCP, but slightly increased by CP. In addition, the two quinolone derivatives had analgesic effects. The analgesic activity of 8-FCP was approximately two times higher than that at CP. However, both 8-FCP and CP had little effects of pentylenetetrazole-or strychnine-induced convulsion and muscle relaxation. Our finding that 8-FCP had more remarkable CNS effects than CP strongly suggests that there should be differences in the pharmacokinetic characteristics and/or in the binding affinity for specific biologic targets, or receptors, in the CNS.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• Toxicological Research
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• v.12 no.2
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• pp.181-194
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• 1996

The effects of Sanjoinine-A, an alkaloid isolated from Zizyphus spinosus semens, on central nervous system and general pharmacology were studied. In summary, Sanjoinine-A depress the spontaneous locomotor activity without motor incoordination and it has slight analgesic effect. Those effects are qualitatively similar to that of diazepam but its potency is much lower than diazepam(20 times). Sanjoinine-A does not depress the electric or pentylenetetrazole induced convulsion. Those effects are dissimilar with that of diazepam. Sanjoinine-A slightly depress the spontaneous or acethylchollne induced motility of smooth muscles but degree of depressant effect was variable to tissues. Sanjoinine-A does not show any effects on digestive system, blood, kidney fuction and neural ganglion.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.287.2-287.2
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• 2002

The safety pharmacological core battery studies of AS2-006A. a newly developed wound healing drug, were investigated according to the ICH S7A guidelines in compliance with Good Laboratory Practice(GLP) Regulations, The doses given were 0, 100. 300 and 1000 mg/kg and drugs were administered subcutaneously. The animals used for this study were mice, rats and guinea pigs. AS2-006A showed no effects on the central nervous system such as motor activity. behaviotal changes. coordination, sensory/motor reflex responses and body temperature. no effects on blood pressure(BP). heart rate(HR), and ECG profiles and respiratory system. it was concluded that AS2-006A possess no general pharmacological effects at all doses tested. (omitted)

• Archives of Obesity and Metabolism
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• v.2 no.2
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• pp.37-44
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• 2023

Weight gain is defined as the increase in body weight, increasing the prevalence of obesity, and results in metabolic diseases. Weight gain was reportedly caused by the interaction between the obesogenic environmental factors and individual metabolic factors. Sociodemographic and environmental factors (demographic factors, lifestyle/behavioral factors, food/nutritional factors, socioeconomic factors), drug-related secondary causes (some of the corticosteroids, antihyperglycemics, antihypertensives, antidepressants, etc.), and metabolic factors (aging and hormonal changes, menopause and decreased sex hormones, decreased adipocyte degradation, decreased fibroblast growth factor 21, central sympathetic nervous system hyperactivity, decreased sympathetic-adrenomedullary system activity) are significant factors related to weight gain. It is crucial to prevent weight gain and maintain an ideal weight, but studies on the risk factors of weight gain are insufficient. Therefore, this study evaluated the factors associated with weight gain to find strategies for preventing unnecessary weight gain.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.67-73
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• 1997

Analgesic effect of DA-5018, a new capsaicin derivative, was evaluated in various rat models of experimentally induced acute pain. DA-5018(0.2∼10.0 mg/kg, p.o.) prevented the writhing syndromes induced by acetic acid or phenol-p-benzoquinone(PBQ). It increased the pain threshold of inflamed paw when tested by the Randall-Selitto method at the dose of 2.0∼20.0 mg/kg by oral administration. And also it showed antinociceptive activities in tail-pinch(1.0∼20.0 mg/kg, p.o.) and tail-flick test(5.0∼50.0 mg/kg, p.o.). the potency and efficacy of DA-5018 were comparable to morphine · HCI in all the models mentioned above. Acetaminophen exhibited the inhibition of acetic acid-induced writhing syndromes and also analgesic activity in Randall-Selitto test, but it showed the limited efficacy in tail-pinch and tail-flick test. These results mean that DA-5018 has a broader analgesic activity profile than acetaminophen. And we found out that the analgesic activity of DA-5018 was 100 times more potent when administered centrally than administered orally in tail-flick test. These results suggest that DA-5018 has an orally active analgesic activity, and central nervous system may be involved in the action of DA-5018.

• Environmental Analysis Health and Toxicology
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• v.19 no.3
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• pp.279-286
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• 2004

Although numerous studies have shown that cadmium disturbs the normal biological processes in central nervous system, the mechanism of toxicity is not well understood. The present study has investigated the effect of cadmium on oxidative stress, Na$^{+}$K$^{+}$ ATPase activity and the aggregation of amyloid beta peptide ($\beta$-amyloid) in neuronal cell line, HT22 cell. LC$_{5}$ and LC$_{50}$ of cadmium for HT22 cell resulted from MTT assay was 4.1 uM and 9.5 uM, respectively. Cadmium (2 to 8 uM) dose-dependently increased the lipid peroxidation and decreased the content of glutathione. Cadmium 4 uM showed a significant decrease in Na$^{+}$/K $^{+}$ ATPase activity as compared with control group. The aggregation of $\beta$-amyloid was accelerated in a dose-dependent manner by the treatment with 2 to 8 uM cadmium. These results suggest that the neurotoxicity of cadmium can be mediated by the increase in oxidative stress and decrease in Na$^{+}$/K$^{+}$ ATPase activity.se activity.

• Food Science of Animal Resources
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• v.32 no.1
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• pp.45-48
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• 2012

The imidazole dipeptide carnosine and its methylated anserine analogues are the major histidine containing dipeptides in vertebrate tissue, especially in skeletal muscle, the heart, and the central nervous system. In this study, the carnosine and anserine content in chicken from different parts and of differing ages was determined and their physiological activities were compared. Anserine was more dominant than carnosine in these tissues and both of them significantly decreased with aging in all parts of chicken muscles. Chicken breast muscle showed the highest content of carnosine and anserine than drumstick and wing. Advanced glycated end-product (AGE) formation was inhibited up to 60% by the extract from 20 wk chicken breast and decreased with aging (90 wk). Anti-oxidation activity was also significantly reduced from 61.2% to 52.9% with aging. As results, anti-glycation and anti-oxidation activity of carnosine and anserine extract from chicken muscle increased proportionally to the amount of those peptides in the muscle, while these decreased with the aging process.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.153-159
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• 1996

${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.