• 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.

• Korean Journal of Medicinal Crop Science
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• v.27 no.2
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• pp.136-142
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• 2019

Background: Agrimonia pilosa Ledeb has been used as a traditional medicine for the treatment of hematuresis and uterine bleeding in Korea. It has been reported to have anti-obesity, anti-diabetes and anti-inflammaotry effect by regulating the inflammatory signaling pathway. However, the preventive effect of Agrimonia pilosa Ledeb on gastritis has not been elucidated. Thus, in the present study, we evaluated the effects of the water extract of Agrimonia pilosa Ledeb (APW) using HCl/EtOH-induced gastritis rat models. Method and Results: Gastritis was induced in rats by HCl/EtOH administration. The rats in each group were orally administered with two doses of APW (100 and 500 mg/kg). Omeprazole was used as a positive control drug. An enzyme-linked immunosorbent assay (ELISA) was used to measure the prostaglandin $E_2$ ($PGE_2$) levels in stomach. The treatment with 500 mg/kg APW reduced the gastric ulcer area. The APW treatment prevented a decreased in $PGE_2$ concentration induced by HCl/EtOH in rats. In the micronucleus test, the ratio of micronucleated polychromatic erythrocytes to polychromatic erythrocytes showed no significant change in the APW-treated group compared with the control group. Conclusions: These results indicate that APW could be used to prevent the gastritis caused by the HCl/EtOH-induced damage to stomach lining. In addition, the APW treatment showed no significant change in results of the micronucleus test. However, further experiments are required to determine how APW influenced the secretion of mucus and gastric acid using the chromosome aberration test and bacterial reverse mutation assay.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.685-696
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• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.282-289
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• 2019

Gastritis is an inflammatory disease involving the stomach and is caused by several factors, including stress, non-steroidal anti-inflammatory drugs such as aspirin, liquor, and Helicobacter pylori. In Korea, Leonurus japonicus Houttuyn (LJW) has been used as traditional medicine for vaginal bleeding, hematuria, and bruise. Previous studies have reported that LJW exhibited hepatoprotective, cardioprotective, and anti-hyperlipidemic effect. However, the effect of the water extract of LJW on gastritis was not elucidated. Thus, we evaluated the anti-gastric effect and genotoxicity of LJW. LJW effectively prevented the degeneration of surface mucous cells and glandular epithelial cells and vascular congestion induced by HCl/EtOH. Micronucleus assay indicated that the rate of micronucleated polychromatic erythrocytes/polychromatic erythrocytes was not significantly different compared that of the control. Further experiments are required to determine the role of LJW in the gastric injury process such as cyclooxygenase signaling pathway and the secretion of mucus in the stomach.

• Journal of Microbiology and Biotechnology
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• v.31 no.11
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• pp.1501-1507
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• 2021

Lagerstroemia ovalifolia Teijsm. & Binn. (LO) (crape myrtle) has reportedly been used as traditional herbal medicine (THM) in Java, Indonesia. Our previous study revealed that the LO leaf extract (LOLE) exerted anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Based on this finding, the current study aimed to evaluate the protective effects of LOLE in a mouse model of LPS-induced acute lung injury (ALI). The results showed that treatment with LPS enhanced the inflammatory cell influx into the lungs and increased the number of macrophages and the secretion of the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of mice. However, these effects were notably abrogated with LOLE pretreatment. Furthermore, the increase of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression in the lung tissues of mice with ALI was also reversed by LOLE. In addition, LOLE significantly suppressed the LPS-induced activation of the MAPK/NF-κB signaling pathway and led to heme oxygenase-1 (HO-1) induction in the lungs. Additionally, in vitro experiments showed that LOLE enhanced the expression of HO-1 in RAW264.7 macrophages. The aforementioned findings collectively indicate that LOLE exerts an ameliorative effect on inflammatory response in the airway of ALI mice.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.83-92
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• 2013

Objectives : Lespedeza Cuneata has been used to treat leukorrhea, asthma, stomach pain, diarrhea, acute mastitis, in Korean traditional medicine. According to recent studies, Lespedeza Cuneata has antioxidation, hypoglycemia, cell protective, insulin secretion, whitening, corpora cavernosa smooth muscle relaxation and antimicrobial activities, but it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Lespedeza Cuneata MeOH extract (LCE) in vivo and in vitro. Methods : In vitro, inflammatory mediators, such as cytokines, nitric oxide and prostaglandin $E_2$ were detected after the addition of LPS with or without LCE in Raw 264.7 macrophage cell line. In vivo, anti-edema effect of LCE was determined in the carrageenan-induced paw edema model in rats. Results : In vitro assay, LCE decreased release of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) via suppression of iNOS and COX-2 expression. LCE inhibited the phosphorylation of $I{\kappa}B$ indicating the suppression of NF-${\kappa}B$ pathway. In vivo assay, LCE significantly inhibited the formation of paw edema induced by carrageenan injection in rats. LCE effectively inhibited increases of hind paw skin thickness and inflammatory cell infilterations. Conclusion : These findings demonstrate that LCE has inhibitory effect on inflammatory mediators in LPS-activated Raw 264.7 cells and on paw edema in carrageenan-stimulated rats, showing the possibility of anti-inflammatory use of Lespedeza Cuneata.

• Journal of Veterinary Science
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• v.24 no.4
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• pp.52.1-52.13
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• 2023

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b⁺CD206⁺ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE₂ pathway.

• Journal of Life Science
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• v.34 no.1
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• pp.9-17
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• 2024

Diabetes mellitus (DM) is one of the main global health problems. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic β-cell is that the characteristic decreases in insulin secretion are caused by regulated apoptotic gene expression. In this study, we examined whether ferulic acid protects INS-1 pancreatic cells against high glucose-induced apoptosis. High glucose concentration (30 mM) induced glucotoxicity and death of INS-1 pancreatic β cells. However, treatment with 1, 5, 10, or 20 μM ferulic acid increased the cell viability in a concentration-dependent manner. Treatment with ferulic acid dose-dependently decreased the intracellular levels of reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide in INS-1 pancreatic β cells pretreated with high glucose. These effects influence the apoptotic pathway, increasing the expression of the anti-apoptotic protein Bcl-2 and reducing the levels of pro-apoptotic proteins, including Bax, cytochrome C, and caspase 9. Annexin V/propidium iodide staining indicated that ferulic acid significantly reduced high glucose-induced apoptosis. These results demonstrate that ferulic acid is a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.1
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• pp.67-75
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• 2024

Skin aging progresses due to external factors such as ultraviolet rays and infections. These factors cause skin fibroblasts to secrete proteolytic enzymes, matrix metalloproteinases (MMPs). MMPs induce the degradation of collagen located in the extracellular matrix, directly influencing aging. The stems of Akebia quinata Decaisne have been reported to have antioxidant and anti-inflammatory effects. However, the anti-aging effect of Akebia quinata Decaisne stem ethanol extract (AQSEE) is not known. Therefore, we studied the TNF-α-induced MMP-1 inhibitory effect in human fibroblasts. When the cell viability of AQSEE was confirmed through MTT asaay, it showed no toxicity up to 400 ㎍/mL. The inhibition of MMP-1 mRNA and protein secretion was confirmed through RT-qPCR and ELISA, and results showed a significant decrease at concentrations of 100, 200, 400 ㎍/mL. We also confirmed by Western blotting that phosphorylation of MAPKs signaling pathway and transcription factors was reduced. As a result, phosphorylation of p38, c-Jun, p65 was significantly decreased at all concentrations. DPPH and ABTS assays were performed to confirm the radical scavenging ability of AQSEE, and the results showed a significant decrease at all concentrations. The results of this study confirmed the MMP-1 inhibitory effect and radical scavenging ability, which suggests that it can be used as an anti-aging substance.