• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.513-520
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• 2023

Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.89-89
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• 2002

In this study, we examined transmission efficiency and expression level of the transgenes in the transgenic mice. The transgenic lines secreting a considerable amount of human lactoferrin(LF) thrombopoietin(TPO), interleukin-10(IL-10) into their milk were subjected to access the inheritance and maintenance of transgenic phenotype. They were bred through three generations. The transmission frequency for each generations(F9, F10, F11) of 3 lines was 38.03±10.43%(13/35), 48.33±3.76%(19/39) and 31.83±8.88%(9/28) in the LF line, 51.33±18.98%(20/38), 63.70±35.71%(12/20) and 29.57± 15.05%(8/26) in the TPO line, 38.27±17.74%(15/37), 47.47±29.88%(14/28) and 50.87±5.85%(14/28) in the IL-10 line, respectively. (omitted)

• Toxicological Research
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• v.30 no.1
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• pp.27-32
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• 2014

Probiotics are live microorganisms that confer a health benefit on the host. Duolac-Gold is a mixture of seven probiotic bacteria containing three species of Bifidobacteria, two species of Lactobacillus, and Streptococcus thermophilus. The aim of this study was to assess the anti-inflammatory effects of Duolac-Gold in an inflammatory bowel disease (IBD) mouse model. IBD was induced by administering 1.5% dextran sulfate sodium (DSS) for 10 days. After induction of DSS-induced colitis, Duolac-Gold was orally administered at three different concentrations. Interestingly, Duolac-Gold treatment accelerated IBD healing, and anti-inflammatory activity was assessed by weight loss, length of the colon, and a microscopic damage score by histology. The expression of inflammatory related cytokines was measured in colon tissues and serum. Of these cytokines, the expression of interleukin-6 decreased remarkably after Duolac-Gold treatment. Taken together, these results suggest that Duolac-Gold treatment is effective in IBD healing by regulating IL-6.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.923-929
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• 2004

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E$_2$ (PGE$_2$), tumor necrosis factor-a (TNF-$\alpha$) and interleukin-1$\beta$(IL-1$\beta$), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE$_2$ production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Cheli-donium majus.

• Biomedical Science Letters
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• v.26 no.4
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• pp.344-350
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• 2020

Asthma is a chronic disease and occurs in airway in the lung. The cause of the disease has not been identified, it is assumed that both genetic and environmental risk factors play an important role in the development of asthma. Interleukin (IL)-12 is a cytokine regulating T-cell and NK cell. In this study, we analyzed the genetic polymorphisms of IL-12 receptor genes (IL-12Rβ1 and IL-12Rβ2) in asthma patients and normal individuals in a Korean population. We analyzed single nucleotide polymorphisms (SNPs) in IL-12Rβ1 and IL-12Rβ2 using the genotype data of 193 asthma cases and 3,228 healthy controls from the Korea Association REsource for their correlation with asthma case. IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant polymorphism association with asthma case. As a results, 16 SNPs from IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant association with asthma. Among them, rs375947 SNP in IL-12Rβ1 showed the greatest statistical correlation with asthma (P-value = 0.028, Odds Ratio = 1.27, 95% Confidence Interval = 1.03~1.57). The groups with minor allele of IL-12Rβ1 and IL-12Rβ2 showed increased risk of asthma. The genotype-based mRNA expression analysis showed that the group of minor allele of IL-12Rβ1 showed decreased mRNA expression. Decreased IL-12Rβ1 expression causes decreased IL-12 signaling, and this affects developing asthma. In conclusion, the SNPs in IL-12Rβ1 and IL-12Rβ2 may contribute to development of asthma in a Korean population.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.535-542
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• 2001

The purpose of this study was to examine the mRNA levels of TNF-${\alpha}$ and IL-6 in the cell lines of normal oral keratocyte and oral squamous cell carcinoma. Total RNA was extracted from these cell lines, observed under UV light, developed by radiographic films of PCR products via reverse transcriptase polymerase chain reaction(RT-PCR) amplication, and measured with densitometer. Each mRNA level of these cell lines divided by ${\beta}$-actin mRNA level was compared to that of normal control group. The results were as follows: 1. Higher mRNA expression of TNF-${\alpha}$ than IL-6 in the normal oral epithelial cell line. 2. In general, expression of mRNA of IL-6 appeared 3-4 times more in tumor cell lines than in control group. 3. mRNA expression of TNF-${\alpha}$ showed variable expression in tumor cell lines, unlike normal cell line. 4. There are no special connections between differentiation of oral cancer cell lines and mRNA expression of TNF-${\alpha}$ and IL-6. From the above results, expression of mRNA of IL-6 in the cell lines of squamous cell carcinoma used in this study has higher than the normal oral epithelial cell line, but there are no relationship between the differentiation of oral cancer cell lines and the expression of mRNA of TNF-${\alpha}$ and IL-6.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.404-413
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• 2019

Udenafil, which is a $PDE_5$ inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafiltreated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and $NF{\kappa}B$. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or $NF{\kappa}B$ knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and $NF{\kappa}B$ pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.

• The Korean Journal of Food And Nutrition
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• v.27 no.3
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• pp.400-405
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• 2014

Recently, cases of Aloe vera induced-toxic hepatitis have been reported. However, the precise inflammatory effects of Aloe vera extract have not been clearly elucidated yet. In this study, the inflammatory effects and the mechanism of 70% ethanolic Aloe vera extract on liver were evaluated by in vitro assays using human hepatoma HepG2 cells. Cell viability was investigated using MTT assay at $0.001{\sim}100{\mu}g/mL$ of Aloe vera extract. To evaluate inflammatory effect of the Aloe vera extract, the secretion of pro-inflammatory cytokine Interleukin 8 (IL-8) and Macrophage colony-stimulating factor (M-CSF) were detected. Aloe vera extract did not induce cell death at concentrations of $0.001{\sim}100{\mu}g/mL$. However, Aloe vera extract significantly increased the IL-8 secretion by 15.7~25.8% and the M-CSF secretion by 36.6~61.5% at the same concentrations. These results indicate that Aloe vera extract shows an inflammation-related mild hepatotoxicity than a severe toxicity such as cell death and this hepatitis is mediated by the secretion of inflammatory cytokine IL-8 and M-CSF.

• Korean Journal of Acupuncture
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• v.27 no.2
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• pp.95-105
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• 2010

Objectives : The purpose of this study is to investigate the effect of Bacillus-fermented Scutellariae Radix acupuncture solution (SB) on interleukin(IL) production in mouse macrophage stimulatedby lipopolysaccaride(LPS). Methods : Productions of interleukins were measured y High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$(multi-analyte profiling beads) technology. To begin with, cell culture supernatant was obtained after treatment with LPS(1 ${\mu}g/mL$) and SB for 24 hour. Then, it was incubated with the antibody-conj${\mu}g$ated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. After incubating for 30 minutes, Strepavidin-conjugated Phycoerythrin(SAPE) was then added. Incubating for another 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System. Results : The results of the experiment are as follows. SB significantly inhibited the LPS-induced production of IL-3($9.15{\pm}0.35$ pg/mL) by $6.92{\pm}0.05,\;7.21{\pm}0.11,\;6.96{\pm}0.33,\;and\;7.45{\pm}0.74$ pg/mL at the concentration of 25, 50, 100, and 200 ${\mu}g/mL$ in mouse macrophage RAW 264.7 cells (p<0.05). SB significantly inhibited the LPS-induced production of IL-5($7.30{\pm}0.48$ pg/mL) by $6.50{\pm}0.29,\;6.30{\pm}0.25,\;6.30{\pm}0.25,\;and\;5.80{\pm}0.25$ pg/mL at the concentration of 25, 50 100, and 200 ${\mg}g/mL$ in RAW 264.7 cells (p<0.05). SB significantly inhibited the LPS-induced productiion of IL-9($17.26{\pm}0.19$ pg/mL) by $15.01{\pm}0.43$ pg/mL at the concentration of 25 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced productioh of IL-13($187.80{\pm}2.90$ pg/mL) by $152.80{\pm}4.25,\;172.80{\pm}3.97,\;162.10{\pm}6.67,\;and\;165.30{\pm}11.80$ pg/mL at the concentration fo 25, 50, 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced production of IL-17($18.30{\pm}0.95$ pg/mL) by $13.30{\pm}1.25,\;13.80{\pm}1.11,\;13.30{\pm}0.75,\;and\;14.00{\pm}1.08$ pg/mL at the concentration of 25, 50 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced production of IL-23($43.90{\pm}0.83$ pg/mL by $39.50{\pm}1.26,\;38.00{\pm}1.78,\;and\;39.60{\pm}2.49$ pg/mL at the concentration of 25, 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). Conclusions : These results suggest that SB has anti-inflammatory activity related with its inhibition of IL-3, IL-5, IL-13, IL-17, and IL-23 production in macrophages.