• Translational and Clinical Pharmacology
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• v.25 no.2
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• Toxicological Research
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• v.35 no.2
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• pp.191-200
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• 2019

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

• Journal of Life Science
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• v.28 no.11
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• pp.1379-1385
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• 2018

Glycans are attached to proteins as in glycoproteins and proteoglycans. They are found on the exterior surface of cells. O- and N-linked glycans are very common in eukaryotic cells but may also be found in prokaryotes. The interaction of cell surface glycans with complementary glycan binding proteins located on neighboring cells, other cell types, pathogens like virus, or bacteria is crucial in biologically and biomedically important processes like pathogen recognition, cell migration, cell-cell adhesion, development, and infection. Their implication in pathological condition, suggests an important role for glycans as disease markers. In addition, a great amount of research has been shown that appropriate glycosylation of a recombinant therapeutic protein is critical for product solubility, stability, pharmacokinetics and pharmacodynamics, bioactivity, and safety. Besides, cancer-associated glycosylation changes often involve sialic acid in glycan branch which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the glycan's biological function and describing the relevance among the glycosylation, disease diagnosis and treatment methods. Furthermore, the high-throughput analytic methods available to measure the profile changing patterns of glycan in the blood serum as well as possible underlying biochemical mechanisms.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.629-635
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• 2018

In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

• The Korea Journal of Herbology
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• v.36 no.5
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• pp.101-108
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• 2021

Objectives : A root of Dipsacus asperoides C. Y. Cheng et T. M. Ai (D. asperoides) has been traditionally used as a medicinal resource in several Asian countries, including Korean and traditional Chinese medicine that has been traditionally used for treating several medical conditions including pain, arthritis, and bone fractures in Korea. In the present study, we investigated potential subacute toxicities of D. asperoides extract. Methods : C57BL/6 mice (male, 7weeks) were randomly divided into 4 groups of 5 mice. Except for the control group, the mice were orally administrated D. asperoides extract at doses of 50, 150, or 450 mg/kg/day for 2 weeks. At the end of the treatment period, all mice were euthanized, and the following parameters were examined: mortality, body weight, clinical signs, gross findings, hematology, serum biochemistry, organ weight, and histopathology. Results : There were no abnormalities in mortality, clinical signs, body weight, gross findings, or organ weight after repeated administration of D. asperoides extract for 2 weeks, compared with the control group. In addition, there were no significant changes in hematological, serum biochemical, and histopathological parameters between the control group and D. asperoides extract administrated groups with doses of up to 450 mg/kg/day. Conclusion : In this study, D. asperoides extract showed no significant toxicities at a dose of up to 450 mg/kg/day in mice. Although we could not confirm the toxic dose of D. asperoides extract, it can be considered safe for further pharmacological use.

• Journal of Life Science
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• v.31 no.1
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• pp.28-36
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• 2021

Edwardsiella piscicida is a significant cause of hemorrhagic septicemia in fish and gastrointestinal infections in humans. Survival bacteria require specialized mechanisms to adapt to environmental fluctuations. Hence, to understand the mechanism through which E. piscicida senses and responds to environmental osmolarity changes, we determined the protein expression profile and physiological properties under various salinity conditions in this study. The OmpR protein is a part of the Env-ZOmpR two-component system that has been implicated in sensing salt stress in bacteria. However, the physiological role played by this protein in E. piscicida remains to be elucidated. Therefore, in this work, the function of the OmpR protein in response to salt stress was investigated. Phenotypic analysis revealed that, in the mutant, three of the biochemical phenotypes were different from the wild type, including, citrate utilization, hydrogen sulfide, and indole production. Introduction of the plasmid containing the entire ompR gene to the mutant strain returned it to its parental phenotype. The retarded growth rate also partially recovered. Furthermore, in our studies, OmpR was not found to be related to cell motility. Taken together, our results from the mutational analysis, the growth assay, MALDI-TOF MS, qRT-PCR, and the phenotype studies suggest that the OmpR of E. piscicida is implicated in osmoregulation, growth, expression of porins (ETAE_1826), virulence-related genes (EseC, EseD and EvpC), and certain genes of unknown function (ETAE_1540 and ETAE_2706).

• Korean Journal of Environmental Agriculture
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• v.40 no.1
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• pp.49-59
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• 2021

BACKGROUND: Soil salinity causes reduction of crop productivity. Rhizosphere microbes have metabolic capabilities and ability to adaptation of plants to biotic and abiotic stresses. Plant growth-promoting bacteria (PGPB) could play a role as elicitors for inducing tolerance to stresses in plants by affecting resident microorganism in soil. This study was conducted to demonstrate the effect of selected strains on rhizosphere microbial community under salinity stress. METHODS AND RESULTS: The experiments were conducted in tomato plants in pots containing field soil. Bacterial suspension was inoculated into three-week-old tomato plants, one week after inoculation, and -1,000 kPa-balanced salinity stress was imposed. The physiological and biochemical attributes of plant under salt stress were monitored by evaluating pigment, malondialdehyde (MDA), proline, soil pH, electrical conductivity (EC) and ion concentrations. To demonstrate the effect of selected Bacillus strains on rhizosphere microbial community, soil microbial diversity and abundance were evaluated with Illumina MiSeq sequencing, and primer sets of 341F/805R and ITS3/ITS4 were used for bacterial and fungal communities, respectively. As a result, when the bacterial strains were inoculated and then salinity stress was imposed, the inoculation decreases the stress susceptibility including reduction in lipid peroxidation, enhanced pigmentation and proline accumulation which subsequently resulted in better plant growth. However, bacterial inoculations did not affect diversity (observed OTUs, ACE, Chao1 and Shannon) and structure (principle coordinate analysis) of microbial communities under salinity stress. Furthermore, relative abundance in microbial communities had no significant difference between bacterial treated- and untreated-soils under salinity stress. CONCLUSION: Inoculation of Bacillus strains could affect plant responses and soil pH of tomato plants under salinity stress, whereas microbial diversity and abundance had no significant difference by the bacterial treatments. These findings demonstrated that Bacillus strains could alleviate plant's salinity damages by regulating pigments, proline, and MDA contents without significant changes of microbial community in tomato plants, and can be used as effective biostimulators against salinity stress for sustainable agriculture.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.1
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• pp.88-95
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• 2021

Aucklandia lappa Decne., a traditional herbal medicine, has been used to treat various diseases, including asthma, coughs, rheumatism, and diarrhea. In the present study, the effects of the oral administration of Aucklandia lappa Decne. extract on hair growth was investigated in hair-removed mice. A 70% ethanol extract of Aucklandia lappa Decne. (ALD) was prepared, and the extraction yield and total polyphenol content of ALD were measured as 27.30±0.01 and 28.39 mg gallic acid equivalent (GAE)/g, respectively. The oral administration of ALD to hair-removed CL57BL/6 mice for six weeks had no significant effects on food intake and body weight changes. Biochemical and histological examinations also showed that the oral administration of ALD for six weeks had no significant effect on the liver and kidney functions. On the other hand, hair growth was significantly higher in the ALD group than the control group and the Pancidil group (positive control). In addition, the number of hair follicles and the degree of collagen production in the dermis were significantly higher in the ALD group than in the control and pancidil groups. These results suggest that ALD is a potential source of nutricosmetics with hair growth-promoting effects.

• The Korea Journal of Herbology
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• v.37 no.1
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• pp.19-29
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• 2022

Objectives : Although the pharmacological effects of anti-inflammatory and antioxidant action of Atractylodes macrocephala Koidzumi water extract (AM) have been proven from many studies, reports on the antioxidant effect of AM on ulcerative colitis (UC) are scarce. Therefore, we aimed at evaluating the anti-oxidant effect of AM on the DSS-induced UC model. Methods : To induce ulcerative colitis, 8-week-old male Balb/c mice received 5% DSS in drinking water for 1 week. After 1 week of adaptation, mice were divided into four groups (n=8 each) for use as normal (Normal), DSS Control (Control), DSS + AM 100 mg/kg (AM100)-treatment, DSS + AM 200 mg/kg (AM200)-treatment. After 1 week of the experiment, the animals were sacrificed, and the extracted colon tissue was analyzed for protein through western blot. Results : As a result of confirming the macroscopic changes in colon tissues to confirm the therapeutic effects of AM, the decrease in colon length was suppressed in the AM treatment group compared to the control group. In addition, as a result of biochemical analysis, AM administration significantly reduced serum glutamic oxalacetic transaminase, glutamic pyruvate transaminase levels and tissue malondialdehyde levels. As a result of confirming the protein expression level through western blot, AM administration significantly decreased the expression of NADPH-related proteins such as NOX2, p22^phox, and iNOS, but significantly increased the expression of SOD, catalase, and GPx-1/2. Conclusions : AM may improve DSS-induced UC in mice by modulating NADPH and antioxidant-related proteins. In conclusion, AM showed an antioxidant effect through the improvement of oxidative stress on UC.

• Journal of Pharmacopuncture
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• v.26 no.1
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• pp.27-37
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• 2023

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.