• Proceedings of the PSK Conference
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• 2001.04a
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• pp.126.1-126.1
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• 2001

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.314.1-314.1
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• 2003

Examination was made of the urinary metabolite(s) of CKD-712, which is a chiral compound, named S-YS49 derived from higenamine (one component of Aconite spp.) derivatives. First of all. to analyze the metabolite(s) of CKD-712, a simple and sensitive detection method for CKD-712 was developed by using gas chromatography-mass spectrometry(GC/MS). (omitted)

• The Journal of Korean Medicine
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• v.40 no.3
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• pp.139-176
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• 2019

Objectives: This study aims to review the herbal medicines containing substances banned by World Anti-Doping Agency(WADA), and to consider criteria for the using of herbal medicines. Methods: Using foreign(Pubmed, Cochrane, Embase, Google Scholar, WANFANG, CiNii) and domestic databases (NDSL, OASIS, RISS), we analyzed the content and pharmacokinetics of the prohibited substances in herbal medicines. Results: Herbal medicines containing the prohibited substances proposed in Korea, China, and Japan are Ephedrae Herba, Cannabis Semen, Strychni Semen, Strychni Ignatii Semen, Pinelliae Tuber, Rhizoma Pinelliae, Chelidonii Herba, Papaveris Fructus Deseminatus, Liriopis Tuber, Rehmanniae Radix Recens, Cistanchis Herba, Ponciri Fructus Immaturus, Aurantii Fructus Immaturus, Moschus, Testudinis Plastrum, Otariae Testis et Penis, and Hominis Placenta. Of these, when using Ephedrae Herba, Cannabis Semen, Strychni Semen, Moschus, Strychni Ignatii Semen, and Otariae Testis et Penis, caution is needed in relation to the doping test. Other herbal medicines are considered safe for the doping test. In addition, by analyzing data related to higenamine added to the WADA's prohibited list of doping since 2017, we don't recommend using Nelumbinis Plumula. And in the case of the other herbal medicines containing higenamine, it is considered that care should be taken in doping test depending on the amount of usage. Conclusions: As a result of analyzing the herbal medicines which are in prohibited list about doping, we were able to know the criteria and precautions to use when prescribing the herbal medicines. Further research will be needed about common used herbal medicines and the amount of detection depending on extraction and boiling method.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.179.1-179.1
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• 2003

CKD-712, named S-YS49 is a chiral compound derived from higenamine (one component of Aconite spp.) derivatives. To compare the cytotoxicity of CKD-712 between in the absence and in the presence of S9 metabolic activation system, we performed try pan blue dye exclusion assay in Chinese hamster lung (CHL) cell. In CHL cells, the cytotoxicity ($IC_{50}$) of CKD-712 was 92.9 ${\m}g$/$m\ell$ and 186.1 ${\m}g$/$m\ell$ in the absence and presence of S9 metabolic activation, respectively. (omitted)

• Biomolecules & Therapeutics
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• v.10 no.2
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• pp.71-77
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• 2002

Heme oxygenase-1 (HO-1) is the inducible from of the rate-limiting enzyme of heme degradation; it regulates the cellular contents of heme. HO-1 is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against oxidative stress in mammalian cells. To investigate the role of the cAMP-dependent protein kinase A (PKA) signaling pathway on nitrogen oxidative stress-induced HO-1 gene expression, RAW 264.7 cell cultures were treated with sodium nitroprusside (SNP). SNP increased the expression of HO-1 mRNA and protein, time- and concentration-dependently. Treatment with H89, PKA inhibitor, but not LY83583, guanylate cyclase inhibitor, significantly diminished the HO-1 expression by SNP, indicating that cAMP plays a crucial role in the induction of HO-1. Incubation with cAMP-elevating agents, such as forskolin or isoproterenol resulted in up-regulation of the expression of HO-1. Forskolin-induced expression of HO-1 was inhibited by H89. Furthermore, propranolol, $\beta$-adrenoceptor blocker, inhibited the isoproterenol-induced HO-1 expression, supporting the importance of cAMP in the induction of HO-1 expression. Higenamine-S, but not higenamineR, enhanced the HO-1 expression induced by SNP. Furthermore, cellular toxicity induced by hydrogen peroxide was attenuated by the presence of SNP, which was further increased by the presence of ZnPPIX, HO-1 inhibitor. Collectively, these results strongly suggest that up-regulation of HO-1 expression in RAW 264.7 cells involves PKA signal pathway.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.88-88
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• 1995

Tetrahydroisoquinoline (THI) compounds have various pharmacological actions in the cardiovascular system. Recently, we have synthesized 1-${\alpha}$-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, YS 49. In the present study, we evaluated the effect of YS-49 on positive inotropic and chronotropic action using isolated rat heart and on blood pressure and heart rate using anesthesized rabbit. Vasodilating action was also assessed in isolated rat thoracic aorta. YS 49, concentration-dependently relaxed rat aorta precontracted with phenylephrine (PE, 0.3 ${\mu}$M) and high potassium (high K$\^$+/, 65.4 mM). The 50% inhibitory concentration (IC$\sub$50/) of YS 49 in PE-induced and high K$\^$+/-induded contraction was 5.36 ${\mu}$M and 2.52 ${\mu}$M, respectively. In isolated rat atria, YS 49 increased both heart rate and force, and in anesthesized rabbit it decreased blood pressure but increased heart rate. In addition, to know the mechanism of action of the compound, propranolol, nonselective ${\beta}$-antagonist, and phentolamine, ${\alpha}$-blocker, were used. Furthermore, a comparison with the effect of higenamine, trimetoquinol on the vasodilating action in rat thoracic aorta was also made. The action of YS 49 was inhibited by the presence of propranolo, not pentolamine. These results indicate that cardiotonic and vasodilatory action of YS 49 is attributable, at least in part, for ${\beta}$-receptor stimulation.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.186-186
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• 2003

CKD-712, named S-YS49 is a chiral compound derived from higenamine (one component of Aconite spp.) derivatives. To compare the cytotoxicity of CKD-712 between in the absence and in the presence of S9 metabolic activation system, we performed trypan blue dye exclusion assay in Chinese hamster lung (CHL) cell. In CHL cells, the cytotoxicity (IC50) of CKD-712 was 92.9 $\mu\textrm{g}$/ml and 186.1 $\mu\textrm{g}$/ml in the absence and presence of S9 metabolic activation, respectively. And we also investigated the induction of DNA damages in mammalian cells. To perform the single cell gel electrophoresis, we determined optimum concentration in mouse lymphoma L5178Y cells using frypan blue dye exclusion assay Each IC20 of CKD-712 was determined the concentration of 23.4 $\mu\textrm{g}$/ml and 24.8 $\mu\textrm{g}$/ml in the absence and presence of S9 metabolic activation, respectively. In the comet assay, DNA damage was not observed at the concentration range from 23.4 $\mu\textrm{g}$/ml to 5.9 $\mu\textrm{g}$/ml in the absence of S9 metabolic activation system. In the presence of S9 metabolic activation system, DNA damage was not observed at the concentration range from 24.8 $\mu\textrm{g}$/ml to 6.2 $\mu\textrm{g}$/ml. From these results, it is assumed that CKD-712 may be metabolized to less cytotoxic metabolite(s).

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.188-188
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• 2003

Examination was made of the urinary metabolite(s) of CKD-712, which is a chiral compound, named S-YS49 derived from higenamine (one component of Aconite spp.) derivatives. First of all, to analyze the metabolite(s) of CKD-712, a simple and sensitive detection method for CKD-712 was developed by using gas chromatography-mass spectrometry GC/MS). Urine was collected from adult male Sprague-Dawley rats 250${\pm}$10g) in metabolic cage for 24hr after oral administration of 100 mg/kg of CKD-712. The recovery of CKD-712 after extraction and concentration with AD-2 resin column was above 90 % from rat urine. The detection limits of CKD-712 in urine was approximately 0.1 ng/mL. It has well been suggested that isoquinoline possessing catechol moiety such as CKD-712 should be subjected to the catechol-O-methyl kransferase activity in vivo. We detected three major peaks of presumed CKD-712 metabolites in the total ion chromatogram obtained from the rat urine sample after oral administration of CKD-712. From these results, it is assumed that the urinary metabolites are mono-methylation in the naphthyl moiety (metabolite I ), methylation at the C-6 or 7 hydroxy group in the isoquinoline moiety and hydroxylation at in the naphthyl moiety (metaboliteII), and methylation at the C-6 or 7 hydroxy group in the isoquinoline moiety (metaboliteIII).

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.325-331
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• 2000

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ plays important roles in inflammatory responses. Some of tetrahydroisoquinoline (THI) compounds exhibited to inhibit iNOS expression in animal studies and RAW 264.7 cells, but the action of THI on inflammatory reaction was not fully investigated. In the present study, we examined a limited series of THIs (higenamine, YS-51 and THI-52) on the $TNF-{\alpha}$ mRNA expression in mouse peritoneal macrophages by Northern analysis. When thioglycollate-stimulated peritoneal macrophages were incubated with LPS (100 ng/ml), expression of $TNF-{\alpha}$ mRNA was evident and reached its maximum at 2.5 h, which was reduced concentration-dependently by treatment with THIs. When the $TNF-{\alpha}$ activity of macrophage-conditioned media was measured using a TNF-sensitive L929 fibroblast cell line, CCL 1, all THIs increased the cell viability in a concentration dependent manner. The concentrations of THIs used are not cytotoxic by itself when analysed by MTT. Furthermore, nitrite/nitrate level was significantly reduced by the presence of THIs in cells treated with $LPS+interferon-{\gamma}\;(IFN-{\gamma}).$ It is concluded, thus, that these results strongly indicated that THIs can suppress the $TNF-{\alpha}$ expression and reduce NO, which may be useful for the inflammatory disorders.