• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.236-254
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• 1996

This study was carried out to investigate the tracheal muscle relaxation of water extracts of three kinds of Coptis rhizoma and also compare their effects with berberine and palmatine, which are the important alkaloid components of Coptis rhizoma, in isolated rat tracheal smooth muscle. As a result Coptis chinenis showed significant tracheal muscle relaxation on KCI-induced contraction and more markedly on carbachol-induced contraction in dose-dependent manner. Coptis japoinin exhibited also tracheal muscle relaxation on both contraction with slightly weaker activities than those of Coptis chinensts. The activities of the root hair of Coptis chinensis were the most weakest in three rhizomas. Berberine and palmatine had strong tracheal muscle relaxation, especially, on carbachol-induced contraction, however, their activities on KCI-induced contraction were weaker than that of Coptis chinenis. The inhibitory effects of three kinds of Coptis rhizoma on the contraction by KCI and carbachol were investigated to explain the process of their tracheal muscle relaxation. All rhizomas inhibited the contraction by both agents, among them, Coptis japonica showed the most significant effect, so indicating that the tracheal muscle relaxation of Coptis rhizoma may be concerned with the blocking of muscarine receptor and $Ca^{2+}$channel.

• Analytical Science and Technology
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• v.30 no.6
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• pp.379-389
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• 2017

In this study, we set up an analytical method that can be used for rapid and accurate determination of representative isoquinoline alkaloids in medicinal plants using UPLC-ESI-Q-TOF MS (ultra pressure liquid chromatography-electrospray ionization-quadrupole-time-of-flight mass spectrometry). The compounds were eluted on a C18 column with 0.1 % formic acid and acetonitrile, and separated with good resolution within 13 min. Each of the separated components was characterized by precursor ions (generated by ESI-Q-TOF) and fragment ions (produced by collision-induced dissociation, CID), which were used as a reliable database. We also performed method validation: analytes showed excellent linearity ($R^2$, 0.9971-0.9996), LOD (5-25 ng/mL), LOQ (17-82 ng/mL), accuracy (91.6-97.4 %) as well as intra- and inter-day precisions (RSD, 1.8-3.2 %). In the analysis of Chelidonium majus L., magnoflorine, coptisine, sanguinarine, berberine and palmatine were detected by matching retention times and characteristic fragment ion patterns of reference standards. We also confirmed that, among the quantified components, coptisine was present in the highest quantity. Furthermore, alkaloid profiling was carried out by analyzing the fragment ion patterns corresponding to peaks of unknown components. In this manner, protopine, chelidonine, stylopine, dihydroberberine, canadine, and nitidine were tentatively identified. We also proposed the molecular structure of the fragment ions that appear in the mass spectrum. Therefore, we concluded that our suggested method for the determination of major isoquinoline alkaloids by UPLC-Q-TOF can be useful not only for quality control, but also for rapid and accurate investigation of phytochemical constituents of medicinal plants.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.345-353
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• 1997

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pre-treatment with ALK or AG, and by post- treatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.443-449
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• 2001

Previously we reported that THI 52 inhibits tumor necrosis factor $(TNF)-{\alpha}$ mRNA expression in mouse peritoneal macrophages exposed to LPS plus $IFN-{\gamma}.$ In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus $IFN-{\gamma}.$ Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.

• Natural Product Sciences
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• v.21 no.4
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• pp.240-247
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• 2015

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

• Molecules and Cells
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• v.42 no.12
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• pp.884-892
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• 2019

Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

• International Journal of Industrial Entomology and Biomaterials
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• v.23 no.1
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• pp.123-128
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• 2011

1-Deoxynojirimycin (DNJ) is an alkaloid that is found at relatively high concentrations in mulberry leaf and tissues of the silkworm, $Bombyx$ $mori$. DNJ is a well known inhibitor of ${\alpha}$-glucosidase, an enzyme that is involved in the early stages of the $N$-linked glycoprotein synthesis pathway. ${\alpha}$-Glucosidase activity in the cell extract from $B.$ $mori$-derived Bm5 cells showed approximately 40-fold less sensitivity to DNJ than ${\alpha}$-glucosidase activity in the cell extract from $Spodoptera$ $frugiperda$-derived Sf9 cells. The replication of $B.$ $mori$ nucleopolyhedrovirus (BmNPV) was not inhibited when it was propagated in BmN cells that were grown in medium containing up to 10 mM DNJ. In contrast, the replication of $Autographa$ $californica$ multiple NPV (AcMNPV) was reduced by 67% when it was propagated in Sf9 cells that were grown in medium containing 10 mM DNJ. The viability of Bm5 and Sf9 cells that were grown in medium containing up to 10 mM DNJ was not affected. Our results suggested that the reduced replication of AcMNPV was the result of the higher sensitivity of ${\alpha}$-glucosidase activity in Sf9 cells to DNJ.

• Journal of the Korean Society of Tobacco Science
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• v.29 no.2
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• pp.59-65
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• 2007

The study was carried out to investigate water activity, physicochemical properties and color degree of burley tobacco stored in shelf with different moisture content for 56 days. The study was consist of two experimental designs, that is, moisture content in burley tobacco was kept to 13 to 15 %, 17 to 19 %, and 21 to 23 % under ambient temperature of $20^{\circ}C$ with relative humidity of 24 %, and another group of in burley tobacco was only kept in ambient temperature of $3^{\circ}C$ with relative humidity of 50 % for 56 days with same water content of former treatment. Normal leaves were kept for 56 days under 21 to 23% of moisture content with increased water activity and TSNA(tobacco-specific nitrosamine content. It was considered that favorable leaves conditions are due to favorable microbial growth resulting in increased TSNA content. The total nitrogen content has not changed in two experimental groups for 56 days, otherwise the nitrate form nitrogen and total alkaloid contents were only increased by 21 to 23 % of water content. Degree of pH change was slightly decreased in both storage and water treatment. It was more decreased in 21 to 23% of moisture content than that of other moisture content. In stored leaf tobacco, higher moisture content caused lower brightness, yellow degree, and carbonization quotient.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• Journal of Applied Biological Chemistry
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• v.58 no.3
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• pp.281-285
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• 2015

Human neutrophil elastase (HNE) represents a good therapeutic target for the treatment of inflammatory diseases as well as invasion of microorganism. The methanol extract of a aerial part of Chelidonium majus L. showed high activity against the neutrophil elastase with an $IC_{50}$ value of $100{\mu}g/mL$. Due to its potency, subsequent bioactivity-guided fractionation of methanol extract led to six alkaloids (1-6), which were identified as dihydrosanguinarine (1), (s)-stylopine (2), arnottianamide (3), (+)-chelidonine (4), spallidamine (5), and N-trans-feruloyltyramine (6). Among of them, three alkaloids (2, 5, and 6) inhibited HNE in a dose-dependent manner with $IC_{50}$ ranging between 11.6 and $51.0{\mu}M$. Lineweaver-Burk and Dixon plots, and their secondary replots showed that alkaloids (2, 5, and 6) were mixed inhibitors of HNE. The analysis of $K_I$ and $K_{IS}$ value proved that all inhibitors (2, 5, and 6) had reversible mixed type I mechanism.