• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.1
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• pp.152-158
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• 2016

Glutamate is one of the major excitatory neurotransmitters in the central nervous system of vertebrates. Human GDH (hGDH) is the enzyme that regulates the glutamate metabolism and its expression is higher in the brains of schizophrenia patients than in normal subjects. This study examined the changes in the hGDH enzymatic activity caused by antipsychotic drugs (haloperidol, risperidone, (${\pm}$)-sulpride, chlopromazine hydrochloride, melperone, (${\pm}$)butaclamol, domperidone, clozapine) related to schizophrenia. First of all, hGDH isozymes (hGDH1, hGDH2) were synthesized by genetic recombination. As a result of the enzyme assay, haloperidol, (${\pm}$)-sulpride, melperone and clozapine had an inhibitory effect on the hGDH isozymes. In addition, haloperidol showed a non-competitive inhibition against the substrate, 2-oxoglutarate. In contrast, it showed an uncompetitive inhibition against another substrate, NADH. The inhibitory effect of haloperidol on hGDH2 was abolished by the presence of L-leucine, an allosteric effector of hGDH, but by not other antipsychotic drugs. These results revealed the inhibition of enzyme activity by psychotropic drugs in hGDH isoenzymes (hGDH1 and hGDH2) and the possibility that haloperidol may be used to regulate the GDH activity and glutamate concentration in the central nervous system.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.208-214
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• 2018

Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

• Korean Journal of Oriental Medicine
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• v.18 no.2
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• pp.101-116
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• 2012

Objectives : This study aims to analyze the papers of the east-west medical combined treatment and suggest the research direction. Methods : 183 research papers were collected by using 25 keywords including combination(in korean words, 병용), collaborative practice(in korean words, 협진) in Korean Medical Database(KMbase) and Oriental Medicine Advanced Searching Integrated System(OASIS). We analysed the type of studies, the kind of diseases, the treatment method, the kind of herbs and drugs in frequent use, and the result of research. Results : Among the analysed 183 papers, clinical studies are 89 cases and experimental studies are 94. 5 cases of clinical studies are Randomized Controlled Trial(RCT). The cancer(50 papers) and diseases of the circulatory system(25 papers) occupied mostly in treatment studies. Because Combined treatment was actively progressed in oriental medicine, treatment was mainly applied the combined oriental medical treatment with herbs and western drugs. In herbal medicine, Mahwangyounpae-tang(麻黃潤肺湯) and Eunkyo-San(銀翹散) were frequently used in the papers. In western drugs, Cyclophosphamide, Cisplatin, and Mitomycin C were frequently used in the papers. 154 papers introduced the treatment effect, 14 papers announced the safety, and 4 papers mentioned the side effect. Conclusions : We suggested several future research direction as follows. Clinical studies based on experiment studies must be more activated and many RCT shoud be shown. Experimental group in clinical studies should be clearly separated to confirm the treatment method is effective or isn't effective. Studies about the side effect must be expanded, and every study should be confirmed both the treatment effect and safety.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.222-228
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• 2020

Background: 20(S)-ginsenoside-Rg3 (C₄₂H₇₂O₁₃), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD₅₀) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

• Journal of Microbiology and Biotechnology
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• v.32 no.8
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• pp.1064-1071
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• 2022

Arabinogalactans have diverse biological properties and can be used as pharmaceutical agents. Most arabinogalactans are composed of β-(1→3)-galactan, so it is particularly important to identify β-1,3-galactanases that can selectively degrade them. In this study, a novel exo-β-1,3-galactanase, named PoGal3, was screened from Penicillium oxalicum sp. 68, and hetero-expressed in P. pastoris GS115 as a soluble protein. PoGal3 belongs to glycoside hydrolase family 43 (GH43) and has a 1,356-bp gene length that encodes 451 amino acids residues. To study the enzymatic properties and substrate selectivity of PoGal3, β-1,3-galactan (AG-P-I) from larch wood arabinogalactan (LWAG) was prepared and characterized by HPLC and NMR. Using AG-P-I as substrate, purified PoGal3 exhibited an optimal pH of 5.0 and temperature of 40℃. We also discovered that Zn²⁺ had the strongest promoting effect on enzyme activity, increasing it by 28.6%. Substrate specificity suggests that PoGal3 functions as an exo-β-1,3-galactanase, with its greatest catalytic activity observed on AG-P-I. Hydrolytic products of AG-P-I are mainly composed of galactose and β-1,6-galactobiose. In addition, PoGal3 can catalyze hydrolysis of LWAG to produce galacto-oligomers. PoGal3 is the first enzyme identified as an exo-β-1,3-galactanase that can be used in building glycan blocks of crucial glycoconjugates to assess their biological functions.

• Korean Journal of Pharmacognosy
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• v.23 no.3
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• pp.158-170
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• 1992

The studies were conducted to investigate the combined effects of several combined preparation of crude drugs and mitomycin C(MMC). The combined effects on the proliferation of Molt-4 cells and activation of human lymphocytes were estimated by MTT colorimetric assays. The drugs itself enhanced the proliferation of Molt-4, but the inhibitory action of MMC was not affected by the combined treatment of the drugs and MMC. Among 9 kinds of the drugs, Sip Jeon Dae Bo Tang(SDT), Saeng Maek San(SMS) and Kwi Bi Tang(KBT) did not inhibit the action of MMC, but activated lymphocytes. When the mice were treated by MMC, the number of leukocytes was decreased significantly at the 1st day, but recovered at the 7th day. In the groups of MMC treated with SDT or KBT, the number of leukocytes was increased significantly than the group of MMC treated only at the 3rd day. The combined treatment of SDT, SMS and MMC retained the body weight of mice at the level of normal mice. The SDT, SMS and KBT did not change the number of plaque forming cells(PFC) and the proliferation of T cells. The combined treatment of SDT and MMC increased the number of PFC significantly than the MMC treated group. The combined treatment of SDT, SMS, KBT and MMC increased the T cell proliferation significantly than the MMC treated group. In conclusion, it is suggested that SDT, SMS and KBT can recover the side effects of MMC, such as weight loss, leukopenia and immunosuppression, without any intercalating the anti-proliferative action of MMC in vivo.

• BMB Reports
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• v.38 no.2
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• pp.198-205
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• 2005

Resveratrol (RES) and genistein (GEN) are the dietary natural products known to possess chemopreventive property and also the ability to repair DNA damage induced by mutagens/carcinogens. It is believed that the therapeutic activity of these compounds could be primarily due to their interaction with nucleic acids but detailed reports are not available. We here explore the interaction of these drugs with nucleic acids considering DNA and RNA as a potential therapeutic target. The interaction of RES and GEN has been analysed in buffered solution with DNA [saline sodium citrate (SSC)] and RNA [tris ethylene diammine tetra acetic acid (TE)] using UV-absorption and Fourier transform infrared (FTIR) spectroscopy. The UV analysis revealed lesser binding affinity with nucleic acids at lower concentration of RES (P/D = 5.00 and 10.00), while at higher drug concentration (P/D = 0.75, 1.00 and 2.50) hyperchromic effect with shift in the ${\lambda}_{max}$ is noted for DNA and RNA. A major RES-nucleic acids complexes was observed through base pairs and phosphate backbone groups with K = $35.782\;M^{-1}$ and K = $34.25\;M^{-1}$ for DNA-RES and RNA-RES complexes respectively. At various concentrations of GEN (P/D = 0.25, 0.50, 0.75, 1.00 and 2.50) hyperchromicity with shift in the ${\lambda}_{max}$ from 260 $\rightarrow$ 263 om and 260 $\rightarrow$ 270 nm is observed for DNA-GEN and RNA-GEN complexes respectively. The binding constant (from UV analysis) for GEN-nucleic acids complexes could not be obtained due to GEN absorbance overlap with that of nucleic acids at 260 nm. Nevertheless a detailed analysis with regard to the interaction of these drugs (RES/GEN) with DNA and RNA could feasibly be understood by FTIR spectroscopy. The NH band of free DNA and RNA which appeared at $3550-3100\;cm^{-1}$ and $3650-2700\;cm^{-1}$ shifted to $3450-2950\;cm^{-1}$ and $3550-3000\;cm^{-1}$ in DNA-RES and RNA-RES complexes respectively. Similarly shifts corresponding to $3650-3100\;cm^{-1}$ and $3420-3000\;cm^{-1}$ have been observed in DNA-GEN and RNA-GEN complexes respectively. The observed reduction in NH band of free nucleic acids upon complexation of these drugs is an indication of the involvement of the hydroxyl (OH) and imino (NH) group during the interaction of the drugs and nucleic acids (DNA/RNA) through H-bonded formation. The interaction of RES and GEN with bases appears in the order of G $\geq$ T > C > A and A > C $\geq$ T > G. Further interaction of these natural compounds with DNA and RNA is also supported by changes in the vibrational frequency (shift/intensity) in symmetrical and asymmetrical stretching of aromatic rings of drugs in the complex spectra. No appreciable shift is observed in the DNA and RNA marker bands, indicating that the B-DNA form and A-family conformation of RNA are not altered during their interaction with RES and GEN.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.220-227
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• 2012

Kidney and liver are the major organs of metabolism and excretion of drugs. Renal and Hepatic impairment may affect the pharmacokinetics/pharmacodynamics and the safety of drugs. Adjusting the dosage based on organ function is the essential role of pharmacists. However, differences have been noted on the recommended dosage among the literatures. We compared and analyzed the recommendations of 4 literature sources which are commonly used for dosage adjustment. From April, 2011 to August, 2011, we selected data on recommendations for dosage adjustment for impaired renal and hepatic function of 100 drugs through a protocol. We analyzed the definition terms of renal and hepatic impairment, recommendations for dosage adjustment, evidenced references in four literature sources: Korean National Formulary (KNF), American Hospital Formulary System Drug Information (AHFS), Micromedex (MM) and Drug Prescribing of Renal Failure (DPRF). We further examined the data homogeneity by comparing how drugs that required no adjustment according to one source were categorized by the other. Sources use different definition terms among themselves except DRPF. Presence or absence of evidenced references about renal/hepatic functional states are KNF (0%/0%), AHFS (78%/62.6%), MM (87.5%/65.6%) and DPRF (93.2%/no recommendation) respectively. Recommendations of specific dosage and dosing interval are KNF (24%/13%), AHFS (39.6%/12.1%), MM (50%/17.7%), and DPRF (55.4%/no recommendation) respectively. Regarding the data homogeneity, the differences were remarkable. Drugs with no adjustment according to AHFS were categorized to be adjusted/ contraindicated by KNF, MM, DPRF and the values were (44%/5.6%), (22%/0%), and (36%/0%) in renal function, (39%/6.5%), (19%/3.2%), and (no recommendation/no recommendation) in hepatic function respectively. Our study shows remarkable definite variation in definitions and recommendations about definition terms, information of dosage and interval, presence or absence of evidenced references. Especially for KNF, quantitative recommendations on dosages and dosing intervals should be made in the near future. To maximize the drug effect and safety and to minimize the heterogeneity of the literature sources, reviewing at least two sources are suggested when recommending the proper dosage adjustment based on organ function.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.2
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• pp.192-196
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• 2012

In the present study, we examined the effect of the aqueous extract of Rubus coreanus Miquel (RCM-Ex) on scopolamine-induced memory impairment in male ICR mice. Mice were fed the diet containing 100 mg/kg body weight/day of RCM-Ex for 4 weeks. To induce amnesia, scopolamine (an antagonist of muscarinic acetylcholine receptor, 1 mg/kg of body weight) was intraperitoneally injected into mice 30 min before starting the behavior tests. RCM-Ex reversed scopolamine-induced memory impairments in mice as evidence by the passive avoidance test and Morris water maze test. In addition, acetylcholineasterase activities were decreased in the brains of mice treated with RCM-Ex. These results suggest that RCM-Ex may be an effective agent for the prevention of the memory impairment induced by cholinergic dysfunction.

• The Korean Journal of Pain
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• v.1 no.2
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• pp.188-191
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• 1988

Recent studies have shown that narcotic drugs produce an intense prolonged analgesic action when injected into the subarachnoidal or extradural space of animals and man. In order to study the effects of intrathecal injection of morphine on postoperative pain relief and segmental block effect, we administered 0.25 mg of morphine sulfate (0.25 mg of morphine/1 ml normal saline) into lumbar subarachnoid space prior to brahial plexus block for upper extremity surgery group The results were as follows: 1) more than 20 hours analgesic effect at least 2) no segemental block effect in analgesia 3) some adverse effect (Nausea, Vomiting, Pruritus, Urinary retention).