• Journal of Nutrition and Health
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• v.53 no.5
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• pp.452-463
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• 2020

Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK. Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion: The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.992-997
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• 2008

Purpose : Hypertension (HTN) is no longer an exclusively adult disease; the prevalence of pediatric HTN is increasing. To understand the evaluation and treatment of childhood HTN in Korea, we investigated, via a questionnaire, how hypertensive children are currently assessed and managed by pediatric cardiologists (CA) and nephrologists (NE). Methods : We surveyed 82 pediatric CA and 77 NE, regarding how they manage hypertensive children in Korea. Results : A total 75 replies were received to our questionnaire request (response rate: 47.15%). Routine blood pressure (BP) checks were more frequently performed by NE (CA: 5.7%, NE: 25%, P=0.03), but most respondents (86%) did not check BP routinely. Mercury sphygmomanometers were the most commonly used devices and ambulatory blood pressure monitoring was not frequently used. The goal BP in treated patients was set at the 95th percentile by 61% of respondents. NE used a lower BP goal in hypertensive children with renal disease (CA: 24%, NE: 64%, P=0.004) or DM (CA: 12.5%, NE: 50%, P=0.003). Angiotensin converting enzyme (ACE) inhibitors were the most commonly used agents (mean: 59%); following ACE inhibitors, CA preferred diuretics for hypertensive children with renal disease or cardiovascular disease, and NE preferred calcium channel blockers, regardless of underlying disease. Self-monitoring was the most frequent method for BP monitoring at home. Conclusion : In Korea, BP measurement is not yet a routine examination in treating hypertension. There are some differences in management strategies vis-$\grave{a}$-vis hypertension, between pediatric cardiologists and nephrologists. For the appropriate management and prevention of secondary disease in long-term studies, standard guidelines and education are needed for pediatricians.

• Journal of Life Science
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• v.27 no.2
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• pp.139-148
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• 2017

The inhibition of tyrosinase, a key enzyme in mammalian melanin synthesis, plays an important role in preventing skin pigmentation and melanoma. Therefore, tyrosinase inhibitors are very important in the fields of medicine and cosmetics. However, only a few tyrosinase inhibitors are currently available because of their toxic effects on skin or lack of selectivity and stability. Therefore, we synthesized a novel series of (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one derivatives and evaluated their inhibitory effects on mushroom tyrosinase, with the aim of discovering a novel tyrosinase inhibitor. Among 19 derivatives, MHY3655 ($IC_{50}=0.1456{\mu}M$) showed the strongest inhibitory effect on tyrosinase activity compared to kojic acid ($IC_{50}=17.2{\mu}M$), a well-known tyrosinase inhibitor. In addition, MHY3655 showed competitive inhibition on Lineweaver-Burk plots. We confirmed that MHY3655 strongly interacts with mushroom tyrosinase residues through the docking simulation. Substitutions with a hydroxy group at both R2 and R4 in the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase. Further, MHY3655 did not show cytotoxicity at the concentrations tested in B16F10 melanoma cells. In conclusion, the novel compound MHY3655 potentially shows tyrosinase inhibitory activity, and it could be used as an ingredient in whitening cosmetics.

• Natural Product Sciences
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• v.5 no.2
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• pp.97-103
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• 1999

The enzyme steroid $5{\alpha}-reductase$ is responsible for the conversion of testosterone into the most potent androgen dihydrotestosterone (DHT). In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Androgen levels in the prostate may influence carcinogenesis in this organ. The use of a $5{\alpha}-reductase$ inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial and have been used successfully for treatment of benign prostatic hyperplasia. Therefore, for the discovery of $5{\alpha}-reductase$ type 2 inhibitors, we have evaluated the inhibitory effects of solvent fractionated extracts of natural products on $5{\alpha}-reductase$ type 2 activity. We have tested approximately 80 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of plants. The ethyl acetate fractions of Perilla sikokiana $(seed,\;IC_{50}\;:\;6.2\;ug/ml)$, Sophora flavescens $(root,\;IC_{50}\;:\;8.9\;ug/ml)$, and Angelica tenuissima $(root,\;IC_{50}\;:\;11.7\;ug/ml)$ revealed inhibitory effects on $5{\alpha}-reductase$ 2 activity in LNCaP cells. The effective ethyl acetate fractions of Perilla sikokiana, Sophora flavescens, Hydnocarpus anthelmintica, and Angelica tenuissima were subfractionated by column chromatography and tested. The subfractions $F4\;(IC_{50}\;:\;1.1\;ug/ml),\;F5\;(IC_{50}\;:\;2.0\;ug/ml),\;and\;F6\;(IC_{50}\;:\;5.8\;ug/ml)$ of the ethyl acetate fraction of Perilla sikokiana and the subfraction $F8\;(IC_{50}\;:\;5.3\;ug/ml)$ of the ethyl acetate fraction of Sophora flavescens displayed greater inhibition of $5{\alpha}-reductase$ type 2 than did finasteride in LNCaP cells. These active fractions are under the process of further sequential fractionation to find the effective pure compounds against $5{\alpha}-reductase$ 2 activity.

• Parasites, Hosts and Diseases
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• v.33 no.4
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• pp.323-330
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• 1995

Protease activity was identified in crude extracts of Pnrqgonimw westermnni eggs which were purified from infected dog lungs, isolated on 14 weeks after metacercarial challenge. The eggs were used after removing possibly contaminated host or worm tissues on their shell surfaces. In the crude egg extracts, high proteolytic activities against carboBfrb enzoyl - ph enylalanyl - arginyl-4- methoxy- β- naphthylamide (Cbz - phe - arg- MNA) and Azocoll were detected whereas those against succinyl-alanyl-propyl-phenylalanyl-p- nitroanilide (Suc-ala-pro-phe-pNA) were not revealed. The eVe eBdlibited the maximal activity at pH 6. Its activity was inhibited by specific cysteine protease inhibitors, 105 M I- trans-epoxysuccinylleucylamido (4-guanidino) butane (E-64) and 1 mM iodoacetamide (LAA) while potentiated by 6.5-fold in the presence of 2.5 mM dithiothreitol (DTT) . When the enzyme was purified partially by Sephacryl S-300 High Resolution gel filtration, it migrated as a single homogeneous band at 35 kDa. The 35 kDa cysteine protease has been recognized neither in the metacercariae nor in the adult. These findings indicated the presence of at least one protease of cathepsin family in immature eggs of f westernani.

• Journal of Life Science
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• v.23 no.9
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• pp.1126-1132
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• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Journal of Life Science
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• v.26 no.4
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• pp.431-438
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• 2016

The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.

• Journal of Life Science
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• v.28 no.2
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• pp.247-256
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• 2018

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

• Korean Journal of Plant Resources
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• v.30 no.2
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• pp.144-151
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• 2017

This study examined the anti-inflammatory and whitening effects of Amaranth (Amaranthus spp L.) seed extract. Amaranthus spp L. seeds were extracted using 70% ethanol and then fractionated sequentially with n-hexane, dichloromethan, ethyl acetate and butanol. For the study of anti-inflammatory activity in RAW 264.7 cells, EtOAc fraction of Amaranthus spp L. seeds significantly inhibited nitrogen oxide production as well as the protein level of iNOS. Furthermore, EtOAc fraction of Amaranthus spp L. seeds inhibited expression of $TNF-{\alpha}$, PGE2 and the protein level of COX-2 in a dose-dependent manner. Inaddition, the tyrosinase inhibitory activities of the Amaranthus spp L. seed 70% ethanol extract and subfractions were also measured to see if these extracts can be used as an ingredient for whitening cosmetics. Tyrosinase is an oxidase that is a rate-limiting enzyme for controlling the production of melanin. Therefore, tyrosinase inhibitors have become increasingly important in cosmetics and medical products with regards to hyperpigmentation. EtOAc fraction of Amaranthus spp L. seeds showed mushroom tyrosinase inhibitory activity in a dose-dependent manner. This activity was more potent than that of a positive control cynandione A. These results suggest that Amaranthus spp L. seeds may be a valuable natural ingredient for the food and cosmetics industries.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.53-61
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• 1995

The experiments were performed to determine whether the cardiac depressant action of lidocaine is directly associated with the utilization of endogenous substrates in isolated rat atria, by using citrate and bicarbonate-free medium known as potent inhibitors of phosphofructokinases (PFK) enzyme step. Citrate and bicarbonate-free medium produced negative inotropic action of isolated rat atria incubated in normal Krebs-Ringer bicarbonate glucose medium. Pyruvate and acetate increased the force of contraction of atria depressed by citrate or bicarbonate-free medium, whereas fructose was without effect indicating the inhibitory effect of citrate and bicarbonate-free medium at some point in the glycolytic pathway such as the PFK step in atria. In the absence of exogenous substrate, citrate and bicarbonate-free medium produced a marked depression of the force of substrate-depleted atria indicating that utilization of endogenous substrate above the PFK step, probably cardiac glycogen, is also impaired by citrate or bicarbonate-free medium. Lidocaine produced further depression of the contractile force of atria depressed by citrate. These results argue strongly for an additional mechanism of cardiac depression caused by lidocaine involving the sites below the PFK.