• Toxicological Research
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• v.29 no.1
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• pp.27-34
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• 2013

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

• Journal of the Korean Wood Science and Technology
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• v.26 no.3
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• pp.73-80
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• 1998

In order to reconstruct the traditional technology of Korean golden varnish coatings, this study was carried out to separate and determine some main coloring components of the exudates of D. morbifera and its traditionally refined golden varnishes using a process of solvent extractions, chromatographies and spectrometries. The results obtained are as follows: 1. The exudate and its traditional-refined golden varnishes appear to have a kind of natural polyacetylenes because it has some triple bond peaks in FT-IR spectrometry. 2. Some yellowing spots of the polar-solvent extrats from the exudates and refined varnishes separated on TLC appeared under natural drying condition, but those of non-polar solvent extract such as hexane did not. 3. A traditional refining method for reconstructing a Korea golden varnishes was thought to be better than solvent separation because the former had higher triple-bond peaks than the latter in FT-IR spectrometry. 4. One of main conponents in the hexane-extracts of the traditional-refined varnishes and the exudates had the same molcular weighr of 204, but the fragmentation patterns was a little different between the exudate and the refined. in LC-MS soectrometry.

• Korean Journal of Medicinal Crop Science
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• v.23 no.5
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• pp.385-394
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• 2015

Background : Dibenzocyclooctadiene lignans are secondary metabolites present abundantly in the fruits belonging to the genus Schisandra. According to previous studies, Schisandra lignans exhibit anti-inflammatory, anti-cancer and anti-diabetic properties, as well as an inhibitory effect on platelet aggregation. Therefore, establishing the Korean "Omija" (Schisandra chinensis) as a lignan-rich source, in addition to identifying and quantifying the lignans, is extremely valuable. Methods and Results : Dibenzocyclooctadiene lignans were analyzed with liquid chromatography using diode array detection/mass spectrometry, from methanol extracts subsequently identified by a constructed chemical library of 50 lignans. A total of 27 components of lignan including gomisin S were identified, of which schisandrin, gomisin A, gomisin N, deoxyschisandrin, ${\gamma}$-schisandrin, and schisandrin C were identified as the major components in the Korean Omija, Schisandra chinensis. These compounds were divided into two groups, S-biphenyl and R-biphenyl based on the configurations of the stereoisomers structures with contents of 661.7 and 1350.1mg per 100 g dry weight, respectively. The total lignan content averaged 2011.4mg per 100 g dry weight, of which schisandrin and gomisin N comprised the majority (771.8 and 420.5mg per 100 g dry weight respectively). Conclusions : Lignans which are present in high quantities in the ripe fruit of Schisandra chinensis are important functional compounds that play a major role in the prevention and treatment of human diseases.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.195-202
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• 2005

Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental factors are critical players in cellular damage and aging. In order to develop a new antiphotoaging agent, this work focused on the antioxidant effects of the extract of tinged autumnal leaves of Acer palmatum. One compound was isolated from an ethyl acetate soluble fraction of the A. palmatum extract using silica gel column chromatography. The chemical structure was identified as apigenin-8-C-beta-D-glucopyranoside, more commonly known as vitexin, by spectral analysis including LC-MS, FT-IR, UV, $^{1}H-$, and $^{13}C-NMR$. The biological activities of vitexin were investigated for the potential application of its anti-aging effects in the cosmetic field. Vitexin inhibited superoxide radicals by about $70\%$ at a concentration of $100\;{\mu}g/mL$ and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals by about $60\%$ at a concentration of $100\;{\mu}g/mL$. Intracellular ROS scavenging activity was indicated by increases in dichlorofluorescein (DCF) fluorescence upon exposure to UVB $20\;mJ/cm^2$ in cultured human dermal fibroblasts (HDFs) after the treatment of vitexin. The results show that oxidation of 5-(6-)chloromethyl-2',7'-dichlo-rodihydrofluorescein diacetate ($CM-H_{2}DCFDA$) is inhibited by vitexin effectively and that vitexin has a potent free radical scavenging activity in UVB-irradiated HDFs. In ROS imaging using a confocal microscope we visualized DCF fluorescence in HDFs directly. In conclusion, our findings suggest that vitexin can be effectively used for the prevention of UV-induced adverse skin reactions such as free radical production and skin cell damage.

• Korean Journal of Medicinal Crop Science
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• v.28 no.4
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• pp.245-253
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• 2020

Background: Research on hot water extracts of medicinal plants that are easily applicable in the clinical setting is essential. To confirm the anti-inflammatory-related active compounds present in the hot water extract of Eriobotrya japonica leaves, ability to inhibit nitric oxide (NO) production was measured and active compounds isolated from the extract were analyzed. Methods and Results: Sovent fractionation by solvent was performed to identify the active compounds present in the hot water extract, and the ability of the extract and the fractions obtained to inhibit NO production was measured. Subsequently, based on the results of liquid chromatography (LC) profile analysis of the n-butanol fraction that had a relatively high inhibitory ability of NO production, six subfractions were separated around the main peak. Among the separated subfractions spectra from mass spectroscopy (MS) were analyzed and standard comparisons were performed on the compounds of the three main peaks on the chromatogram. NO production inhibitory activity of subfraction 2 identified as neochlorogenic acid was the highest with an IC₅₀ of 18.49 ㎍/㎖ followed by that of subfraction 5 identified as cryptochlorogenic acid with IC₅₀ of 25.82 ㎍/㎖. Conclusions: Our result, it was confirmed that several caffeoylquinic acids, including neochlorogenic acid and cryptochlorogenic acid present in the hot water extract of E. japonica leaves have an important role as compounds exhibiting anti-inflammatory activity.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.21-29
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• 2019

The effects of Lavandula angustifolia extract fermented with Pediococcus pentosaceus DK1 on UVB-mediated MMP-1 expression and collagen decrease in human skin fibroblasts were determined, and the conversion of its components was also analyzed. Fermentation was performed at varying L. angustifolia extract and MRS medium concentrations, and optimal fermentation conditions were selected. L. angustifolia extracts showed decreased cytotoxicity after fermentation in the fibroblasts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extract showed MMP-1 expression 8.2-14.0% lower than that in UVB-irradiated fibroblasts treated with non-fermented extract. This was observed even at fermented extract concentrations lower than those of non-fermented extracts. Fibroblasts treated with fermented L. angustifolia extract showed 20% less reduction in collagen production upon UVB irradiation than those treated with non-fermented extracts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extracts showed 50% higher inhibition of ROS generation than those treated with non-fermented extract. Luteolin and apigenin glycosides of L. angustifolia were converted during fermentation, and identified using RP-HPLC and LC/ESI-MS. Therefore, the effects of L. angustifolia extract on MMP-1 expression and collagen decrease in UVB-irradiated human skin fibroblasts were increased through fermentation by P. pentosaceus.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.430-436
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• 2022

Platycosides, Platycodi radix (Platycodon grandiflorus root) saponins, are used as food supplements and exert diverse pharmacological activities. Deglycosylation of saponins enhances their biological efficacy, and deglycosylated platycosides are produced mainly through enzymatic hydrolysis. However, the types of available deglycosylated platycosides remain limited because of a lack of hydrolyzing enzymes that can act on specific glycosides in glycosylated platycosides. In this study, a crude enzyme from Aspergillus tubingensis converted platycoside E (PE) and polygalacin D₃ (PGD3) into deglucose-apiose-xylosylated (deGAX)-platycodin D (PD) and deGAX-polygalacin D (PGD), respectively. The products were identified through LC/MS analysis by specifically hydrolyzing all glucose residues at C-3, and apiose and xylose residues at C-28 of platycoside. The hydrolytic activity of the crude enzyme obtained after the cultivation of the fungus using citrus pectin and corn steep solid as carbon and nitrogen sources, respectively, in culture medium was increased compared with those using other carbon and nitrogen sources. The crude enzyme from A. tubingensis was the most effective in producing deGAX platycoside at pH 5.0 and 60℃. The crude enzyme produced 0.32 mg/ml deGAX-PD and 0.34 mg/ml deGAX-PGD from 1 mg/ml PE and 1 mg/ml PGD3 (at pH 5.0 and 60℃) for 12 and 10 h, with productivities of 32.0 and 42.5 mg/l/h and molar yields of 62.1 and 59.6%, respectively. To the best of our knowledge, this is the first study to produce deGAX platycosides from glycosylated platycosides.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1437-1447
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• 2023

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

• Journal of Applied Biological Chemistry
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• v.61 no.1
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• pp.83-91
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• 2018

Advances in bacterial and fungal genome mining uncover a plethora of cryptic secondary metabolite biosynthetic gene clusters. Guided by the genome information, targeted transcriptional derepression could be employed to determine the product of a cryptic gene cluster and to explore its biological role. Monascus spp. are food grade filamentous fungi popular in eastern Asia and several genome data belong to them are now available. We achieved transcription activation of a cryptic fungal polyketide synthase-nonribosomal peptide synthase gene Mpfus1 in Monascus purpureus ${\Delta}MpPKS5$ by inserting Aspergillus gpdA promoter at the upstream of Mpfus1 through double crossover gene replacement. The gene cluster with Mpfus1 show a high similarity to those for the biosynthesis of conjugated polyene derivatives with 2-pyrrolidone ring and the mycotoxin fusarin is the representative member of this group. The ${\Delta}MpPKS5$ is incapable of producing azaphilone pigment, providing an excellent background to identify chromogenic and UV-absorbing compounds. Activation of Mpfus1 resulted in a yellow hue on mycelia and its methanol extract exhibit a maximum absorption at 365 nm. HPLC analysis of the organic extracts indicated the presence of a variety of yellow compounds in the extract. This implies that the product of MpFus1 is metabolically or chemically unstable. LC-MS analysis guided us to predict the MpFus1 product and to propose that the Mpfus1-containing gene cluster encode the biosynthesis of a desmethyl analogue of fusarin. This study showcases the genome mining in Monascus and the possibility to unveil new biological activities embedded in it.