• Biomolecules & Therapeutics
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• 제1권2호
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• pp.211-219
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• 1993

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine ($10^{-6}g/mι$), histamine ($10^{-6}g/mι$) and $BaCl_2$ ($10^{-4}g/mι$) at a concentration of $1.9{\times}10^{-4}g/mι$ in bath. But it caused a slight increase in basal tone at a concentration of $6.3{\times}10^{-4}g/mι$ and this effect was inhibited by atropine $10^{-7}g/mι.$ In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions produced by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility, But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

• BMB Reports
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• 제35권5호
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• pp.482-487
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• 2002

Early activation of human peripheral blood polymorphonuclear neutrophils is characterized by their morphological changes from spherical to polarized shapes. The endotoxins from enteric pathogens (S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae) were assessed by their ability to induce morphological polarization of the neutrophils as measures of early activation. Phagocytic activity, adhesion, chemokinetic locomotion, and nitroblue tetrazolium (NBT) dye-reduction ability measured the later activation of the cells. Neutrophils showed distinct morphological polarization in suspension over a wide range of concentrations of these endotoxins when were compared with those that were induced by the standard chemotactic factor, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It was discovered that all of the endotoxins induced locomotor responses in neutrophils in suspension that were dose- and time-dependent. The optimum concentration for the endotoxins of S. dysenteriae, V. cholerae, and K. pneumoniae was 1 mg/ml in which 71, 69, and 66% of the neutrophils were polarized. However, the S. typhimurium dose was 2 mg/ml in which 50% of the cells responded. Neutrophils that were stimulated with endotoxins also showed increased random locomotion (p<0.005) through cellulose nitrate filters, but an enhanced adhesion of the cells to glass surfaces (p<0.03). These are important functions of these cells to reach and phagocytose damaged cells, as well as invading microorganisms. Interestingly, the endotoxins had a highly-significant inhibitory effect upon the proportions of neutrophils phagocytosing opsonized yeast (p<0.01) with a small number of yeast that were engulfed by the cells (p<0.02). Further, endotoxin-treated cells showed an enhanced ability to reduce NBT dye (p<0.03). Therefore, we concluded that endotoxins of enteric pathogens are neutrophil chemotactic factors.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.84-89
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.

• 대한한의학방제학회지
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• 제22권1호
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• pp.105-112
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• 2014

Background and objective: Methamphetamine (Meth) is a widely abused psychostimulant that produces hyperlocomotion in rodents. Radix of Glycyrrhizae uralensis comprises a variety of bioactive components that have neuroprotective effects. In a previous study, we have demonstrated methanol extracts from radix of Glycyrrhizae uralensis (MEGR) suppress acute cocaine-induced extracellular dopamine release in the nucleus accumbens. In the present study, we investigated the effect of MEGR on acute Meth-induced hyperlocomotion. Methods: Male Sprague-Dawley rats were orally administered with MEGR (60 mg/kg and 180 mg/kg) 60 min prior to an intraperitoneal injection of Meth (1.0 mg/kg). Results: Behavioral analysis showed acute Meth greatly increased locomotor activities, while pretreatment with MEGR dose dependently inhibited the hyperlocomotion. In parallel, there were markedly increased levels of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the nucleus accumbens tissues in Meth-treated rats, which were also almost completely reversed by 180 mg/kg MEGR. Conclusions: These results showed that radix of Glycyrrhizae uralensis attenuates Meth-induced hyperlocomotion by inhibiting dopamine synthesis and utilization, suggesting that radix of Glycyrrhizae uralensis might be effective in blocking the rewarding effect of Meth.

• The Journal of Korean Physical Therapy
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• 제24권6호
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• pp.423-427
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• 2012

Purpose: The cerebellum is a region of brain structure that plays an important role in calibrating two different information of neural signal from descending motor commands and from ascending sensory inputs. Damage of the cerebellum shows a variety of classic motor symptoms such as postural and locomotor dysfunctions. Therefore, we tried to investigate motor function and skill in stroke patients with cerebellar lesions in sub-acute stage, and compare with these functions of patients with non-cerebellar lesions. Methods: Total twelve stroke patients with cerebellar lesion and 130 stroke patients with non-cerebellar lesions were retrospectively recruited in this study. For evaluation of motor strength, Motricity index (MI) for upper and lower limbs was tested. For measurement of motor skill function, the modified Brunnstrom classification (MBC), Manual function test (MFT), functional ambulatory category (FAC), and Barthel index were adopted. Results: In comparison of motor strength and motor skill function between two groups, statistical differences between the two groups were significantly observed only in upper MI and FAC. Although no significant differences were found in other variables, stroke patients with cerebellar lesion had higher scores in lower and total MI, MBC, and MFT, whereas they had lower scores in FAC and Barthel index. Conclusion: Our results showed that stroke patients with cerebellar lesion had greater impact on movement functions related to hand motor and walking ability in activities of daily life, compared with patients with non-cerebellar lesion, in spite of similar degree of motor function and skill between the two different lesioned-groups.

• Natural Product Sciences
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• 제15권3호
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• pp.115-120
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• 2009

Woohwangcheongsimwon (WHCSW) is a traditional oriental medicinal fomula which has been clinically used for treating strokes, palpitation, loss of consciousness and anxiety. The purpose of this study was to characterize the putative anxiolytic properties of WHCSW using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). In the EPM test, WHCSW significantly increased the percentage of time-spent in the open arms (200 mg/kg, P < 0.05) and the percentage of open arm entries (200 and 400 mg/kg, P < 0.05). WHCSW also significantly increased the number of head-dips in the hole-board test (200 mg/kg, P < 0.05). In addition, the anxiolytic properties of WHCSW examined in the EPM test were inhibited by flumazenil (10 mg/kg, i.p.), a GABA$_A$ antagonist. However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus 10% Tween 80 controls. These results suggested that WHCSW is an effective anxiolytic agent, and that its anxiolytic effects are mediated via GABA$_A$ receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• The Korean Journal of Physiology and Pharmacology
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• 제15권6호
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• pp.389-395
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• 2011

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or $2.0{\mu}g/side$), or U0126 (0.1 or $1.0{\mu}g/side$), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 ($2.0{\mu}g/side$) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

• 동의생리병리학회지
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• 제34권2호
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• pp.88-96
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• 2020

Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) are herbal extracts widely used in food and traditional herbal medicine, and have the ability to perform a wide range of biological activities. We aimed to investigate the effects of the SH and VB combination (SHVB) on mice models of chronic restraint stress (CRS) and pentobarbital-induced sleeping behaviors to elucidate its possible mechanisms of action. CRS-exposed mice treated with SHVB showed significantly decreased immobility time, increased swimming and climbing times in the forced swim test (FST), and increased locomotor activity in the open field test (OFT). SHVB decreased serum CORT levels, but enhanced brain monoamine neurotransmitters. SHVB significantly decreased the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behavior in mice. SHVB showed inhibitory effect on 5-HT_2A receptor-mediated ERK1/2 phosphorylation. These results suggest that SHVB has antidepressant and hypnotic effects by regulating the 5-HT_2A receptor.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.