• The Korea Journal of Herbology
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• v.32 no.1
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• pp.15-23
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• 2017

Objectives : It is well known that Sibjotang (Shizaotang), traditional herbal medicine formula, regulates the body fluid blood pressure homeostasis. This study is to investigate whether Sibjotang improves diabetic renal dysfunction in type II diabetes mellitus animal model, db/db mice. Methods : The animals model were divided into three groups at the age of 8 weeks; control group (C57BLKS/J-db/m mice), diabetic group [(C57BLKS/J+Lepr)-db/db mice], and Sibjotang group [(C57BLKS/J+Lepr)-db/db mice + Sibjotang 100 mg/kg/day]. During 8 weeks of treatment, blood glucose and urinary albumin excretion were checked in metabolic chamber at 8, 12, and 16 weeks of age, respectively. Results : Body weight and food intake of diabetic group were significantly higher than control group after 8 weeks administration. However, there were not significant different between the diabetic group and Sibjotang group. Urinary albumin excretion was significantly decreased in the Sibjotang group than the diabetic group. In addition, supplementation with Sibjotang significantly lowered levels of blood glucose, insulin, and homeostatic model assessment-insulin resistance (HOMA-IR), suggesting reduced insulin resistance. The ratio of mesangial matrix/glomerular area was markedly larger in diabetic group than control group, whereas Sibjotang significantly reduced this expansion. Moreover, immunohistological study revealed that Sibjotang attenuated the increase of transforming growth $factor(TGF)-{\beta}$ expression in kidney. Conclusion : Sibjotang ameliorates diabetes-associated renal injury through the improvement of the blood glucose and insulin sensitivity, and inhibiting the $TGF-{\beta}1$ expression. Therefore, Sibjotang may be a new therapeutic formula for the treatment of diabetic-associated renal dysfunction.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.2
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• pp.49-70
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• 2017

Objectives: The present study is to observe the skin-regeneration, anti-wrinkle, whitening and skin moisturizing effects of Cheongsangbangpung-tang (CSBPT) with cytotoxicity. Methods: In the present study, cytotoxicity of CSBPT lyophilized aqueous extracts (yield=18.71%) was experimented against human normal fibroblast cells and B16F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also showed through the assay of collagen type I synthesis by an enzyme immunoassay (EIA) kit as comparing with transforming growth factor (TGF)-${\beta}1$, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays as comparing with oleanolic acid (OA), and elastase inhibitory effects as comparing with phosphoramidon disodium salt (PP). In addition, whitening effects of CSBPT were observed by tyrosinase inhibitory assay and melanin formation test in B16/F10 melanoma cells as comparing with arbutin, and skin moisturizing effects were measured through mouse skin water contents test, respectively. Results: No CSBPT treatment related cytotoxic effects were demonstrated against human normal fibroblast cells and B16/F10 murine melanoma cells. CSBPT concentration-dependent increased collagen type I synthesis at human normal fibroblast cells. It also effectively suspreessed hyaluronidase, collagenase, elastase and MMP-1 activities, which were enzymes that related to declining of ECM and formation of wrinkle. CSBPT supressed B16/F10 melanoma cells's melanin productions with tyrosinase activity, which was an enzyme connected with melanin formation, and dose-dependent and significant increases of skin water contents were detected in CSBPT treated mouse skin as compared with vehicle control skins. Conclusions: CSBPT showed favorable and enough skin regeneration, anti-wrinkle, whitening and skin moisturizing effects at least in a condition of this experiment. However, more detail mechanism and in vivo skin protective efficacy studies should be conducted in future with the screening of the biological active compounds in individual herbs of Cheongsangbangpung-tang.

• Food Science of Animal Resources
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• v.32 no.3
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• pp.339-345
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• 2012

This experiment was carried out in order to separate bovine colostral whey protein from Imsil province and to test the effect of immunological activity on RAW 264.7 cells. The colostral whey protein contained TGF-${\beta}$ 7, 475 pg/g in total. We first tested the effect of the colostral whey protein on the proliferation of RAW 264.7 cells and it demonstrated cytotoxicity at concentrations greater than 20 mg/mL. Therefore, the immunological activities of colostral whey protein were investigated in maximum concentration of 10 mg/mL on LPS-induced RAW 264.7 cells. Results indicated that colostral whey protein inhibited the LPS-induced nitric oxide (NO) production in a dose-dependent manner. The colostral whey protein also suppressed the productions of proinflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in a dose-dependent manner. In addition to the immunological activity, colostral whey protein led to the expression of heme oxygenase-1 (HO-1) in RAW 264.7 cells. In conclusion, colostral whey protein containing TGF-${\beta}$ inhibited the production of NO, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 via expression of HO-1.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.94-110
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• 2010

Objective : This study was performed to evaluate the effect of immune reaction inductive substances such as phorbol-myristate-acetate(PMA), lipopolysaccharide(LPS), dermato-phagoides pteronyssus crude extract(DPE), dinitrochloro-benzene(DNCB) and Cryptotympana pustulata(CP), the Cryptotympana pustulata extracting substance at simultaneously on the translocation of nuclear factor-kappa B(NF-${\kappa}B$) towards to the nucleus and the mRNA expression patterns of various cytokine genes in Human acute monocytic leukemia cell line(THP-1 cells), monocytes of human. Experiment : To analyze cytokine genes expression patterns, the RT-PCR method was used, measuring tumor necrosis factor(TNF)-$\alpha$ that had been secreted during cell culture in the ELISA method. The morphological change in the cell observed during THP-1 cell culture was observed using a scanning electron microscope (SEM) and the quantitative distribution in the cell NF-${\kappa}B$ was analyzed through immunocytochemistry and a confocal microscopy. Result : CP showed different influences onto the mRNA expression patterns of cytokine genes with PMA, LPS. DPE and DNCB according to the types of immune inductive substances in the THP-1 cells. The expressions of inter-leukin(IL)-10, interferon(INF)-$\gamma$, TNF-$\alpha$ and monocyte chemoattractantant protein(MCP)-1 induced by PMA were suppressed by CP while the expression of transforming growth factor(TGF)-$\beta$ was promoted. Regarding the secretion pattern of TNF-$\alpha$ according to PMA processing, its secretion amount was increased by CP concurrent processing, in case of processing CP onto PMA and LPS, We discovered that the secretion amount of TNF-$\alpha$ was increased. Upon processing PMA and LPS on the THP-1 cell strain at the same time or either additionally processing CP thereon, the movement increase towards the nucleus from the NF-${\kappa}B$ cell cytoplasm, a transcription factor was able to be observed. Conclusion : In this study, Cryptotympana pustulata extracting substance was confirmed that it had an influence on expression patterns of cytokine genes according to the actions of a variety kinds of immune reaction inductive substances processed on the monocyte THP-1 cell of humans. Therefore, additional studies as for the immune adjusting function of Cryptotympana pustulata are considered to be able to offer important materials for curing immune abnormal diseases such as atopy dermatitis afterward.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.177-184
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• 2020

Objectives : Postpartum depression is known to occur in 10-15% of mothers. The concentration of cytokine varies depending on stress, depression, pregnancy and general medical conditions. We hypothesized that the concentration of cytokines may be related to reproduction and childbirth, and that women with postpartum depression would show alterations in cytokines levels. Methods : A total of 104 pregnant women were selected as subjects, and 60 non-pregnant women were selected as normal controls. Symptoms of depression were evaluated in the pregnant study subjects using the diagnostic criteria outlined in the Edinburgh Postnatal Depression Scale (EPDS). The pregnant subjects were divided into three groups perinatal non-depression controls (n=61), postpartum depression-recovery (n=18), and postpartum depression (n=25). Results : The plasma concentration of TGF-β1, IGF-1 was higher in the pregnant group than in non-pregnant controls (TGF-β1 ; p<0.01, IGF-1 ; p=0.026). At 24 weeks of pregnancy and 6 weeks of delivery, there were no significant differences in the plasma concentration of TGF-β1, IGF-1, β-NGF, IL-2, IL-4, IL-6, IFN-γ, TNF-α between the three groups. There was no statistically significant difference in all three groups during the course of depression in pregnant women. Conclusions : This study found significant difference in plasma cytokines concentrations between non-pregnant controls and perinatal non-depression controls.

• Journal of Nutrition and Health
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• v.53 no.1
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• pp.1-12
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• 2020

Purpose: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway. Methods: Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1-20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis. Results: High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1-20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin. Conclusion: These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.133-142
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• 2019

Background: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. Methods: Mouse AE II cell line MLE-12 were exposed to $1-10{\mu}g/mL$ BLM and $0.01-100{\mu}M$ baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. Results: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor ${\alpha}$, and transforming growth factor ${\beta}1$. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. Conclusion: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.140-153
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• 2003

Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

• Journal of Life Science
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• v.25 no.12
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• pp.1425-1431
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• 2015

The lymphocyte component of the immune system is divided into B lymphocytes and T lymphocytes. B lymphocytes produce antibodies (humoral immunity) via maturation into plasma cells, and T lymphocytes kill other cells or organisms (cellular immunity). A traditional immunological paradigm is that B lymphocyte and T lymphocyte interactions are a one-way phenomenon, with T lymphocytes helping to induce the terminal differentiation of B lymphocytes into immunoglobulin class-switched plasma cells. A deficiency of T lymphocytes was reported to result in defective B lymphocyte function. However, evidence for a reciprocal interaction between B and T lymphocytes is emerging, with B lymphocytes influencing the differentiation and effector function of T lymphocytes. For example, B lymphocytes have been shown to induce direct tolerance of antigen-specific CD8⁺ T lymphocytes and induce T lymphocytes anergy via transforming growth factor-beta (TGF-β) production. The present study showed that LPS-stimulated B lymphocytes inhibited the differentiation of Th1 lymphocytes by inhibiting the production of interleukin-12 (IL-12) from dendritic cells. An interaction between the B lymphocytes and dendritic cells was not needed for this inhibition, and the B lymphocytes did not alter dendritic cell maturation. B lymphocyte-derived soluble factor (BDSF) suppressed the LPS-induced IL-12p35 transcription in the dendritic cells. Overall, these results point to a novel B lymphocyte- mediated immune suppressive mechanism. The findings cast doubt on the traditional paradigm of immunological interactions involving B lymphocyte and T lymphocyte interactions.