• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.6
• /
• pp.533-543
• /
• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• The Korea Journal of Herbology
• /
• v.37 no.1
• /
• pp.41-50
• /
• 2022

Objectives : The aim of this study was to investigate the effect of water extract of Agastache rugosa (AR) on productions of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages. Methods : Cell viabilities were measured with MTT assay. The production of nitric oxide (NO) from RAW 264.7 cells was measured with Griess reagent assay. The production of cytokines in RAW 264.7 cells was measured with multiplex cytokine assay. Results : AR showed no cytotoxicity on RAW 264.7 cells. AR at concentrations of 25, 50, 100, and 200 ㎍/mL significantly inhibited NO production in LPS-stimulated RAW 264.7 cells. AR at concentrations of 50, 100, and 200 ㎍/mL significantly inhibited productions of TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells; AR at concentrations of 50 and 200 ㎍/mL significantly inhibited productions of RANTES (CCL5) in LPS-stimulated RAW 264.7 cells; AR at concentrations of 100 ㎍/mL significantly inhibited productions of macrophage inflammatory protein-1β in LPS-stimulated RAW 264.7 cells; AR at concentrations of 50, 100, and 200 ㎍/mL significantly increased productions of IP-10 (CXCL10) in LPS-stimulated RAW 264.7 cells; AR at concentrations of 100 and 200 ㎍/mL significantly increased MCP-1 (CCL-2) in LPS-stimulated RAW 264.7 cells; AR at concentrations of 50 and 100 ㎍/mL significantly increased productions of IL-10 in LPS-stimulated RAW 264.7 cells. Conclusions : AR might have immunomodulatory effects on productions of NO, cytokines, and chemokines in LPS-stimulated RAW 264.7 mouse macrophages.

• Journal of Animal Reproduction and Biotechnology
• /
• v.38 no.1
• /
• pp.17-25
• /
• 2023

Brassica oleracea var. italica (broccoli) is a type of cabbage that contains vitamins, minerals, and phytochemicals. Consequently, it is used as a potential nutraceutical source for improving human health by reducing oxidative stress and inflammatory responses. Here, the effects of broccoli sprout extract (BSE) on the inflammatory response were investigated through lipopolysaccharide (LPS)-induced inflammatory mouse models. First, we found that the BSE obviously reduce NO production in RAW 264.7 cells in response to LPS stimulation in in vitro study. Pretreatment with BSE administration improved sperm motility and testicular cell survivability in LPS-induced endotoxemic mice. Additionally, BSE treatment decreased the levels of the pro-inflammatory cytokines TNF-a, IL-1β, and IL-6, and COX-2 in testis of LPS-induced endotoxemic mice models. In conclusion, BSE could be a potential nutraceutical for preventing the excessive immune related infertility.

• Korean Journal of Clinical Laboratory Science
• /
• v.50 no.3
• /
• pp.304-312
• /
• 2018

Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived $TGF-{\beta}1$ on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with $4{\times}10^6$ Treg cells for 48 hours. The changes in $TGF-{\beta}1$, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P<0.0005, P<0.005) and islet viability was improved (P<0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the $TGF-{\beta}1$ secretion pathway (P<0.05~0.005), thus the use of Treg in islet transplantation should be explored further.

• International Journal of Oral Biology
• /
• v.41 no.3
• /
• pp.125-131
• /
• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• Korean Journal of Pharmacognosy
• /
• v.52 no.1
• /
• pp.34-40
• /
• 2021

Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

• Korean Journal of Food Science and Technology
• /
• v.54 no.2
• /
• pp.155-162
• /
• 2022

This study investigated the immunostimulatory effect of enzymatic porcine placental hydrolyzate (EPPH) in cyclophosphamide (Cy)-treated rats. This effect of EPPH prevented Cy-induced decreases in body, spleen, and thymus weights and natural killer (NK) cell activity. The numbers of immune cells, such as white blood cells, granulocytes, and lymphocytes, and mid-range absolute counts were significantly higher compared to the control group. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-2, IL-12, and immunoglobulin G (IgG) were notably reduced by Cy, while EPPH prevented these effects. Histopathological analysis of spleen samples revealed the protective effect of EPPH against Cy-induced immunosuppression. The findings demonstrate that EPPH can alleviate immunosuppression by cell viability, tissue damage, and regulation of the levels of cytokines. EPPH may have value as a component of immunostimulatory agents or an ingredient in functional foods.

• Journal of Oriental Neuropsychiatry
• /
• v.21 no.2
• /
• pp.171-189
• /
• 2010

Objectives : This research investigates the effect of the HBSBS on Alzheimer's disease. Specifically, the effects of the HBSBS extract on (1) the behavior (2) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's disease mice induced with $\beta$A were investigated. Methods : The effects of the HBSBS extract suppressed the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and NOS-II mRNA in BV2 microglial cell line treated with LPS plus $\beta$A were investigated. The effects of the HBSBS extract on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The HBSBS extract suppressed the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and NOS-II mRNA in BV2 microglial cell line treated with LPS plus $\beta$A. 2. The HBSBS extract suppressed the expression of $\beta$A protein production in BV2 microglial cell line treated with LPS plus $\beta$A. 3. The HBSBS extract showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. 4. The HBSBS group suppressed the over-expression of IL-1$\beta$ protein, TNF-$\alpha$ protein significantly in the mice with Alzheimer's disease induced by $\beta$A. 5. The HBSBS group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by $\beta$A. 6. The HBSBS group reduced tau protein, and GFAP in the brain tissue of the mice with AD induced by $\beta$A. Conclusions : These results suggest that the HBSBS group may be effective for the treatment of AD. Thus, HBSBS could be considered among the future therapeutic drugs indicated for the treatment of AD.

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

• Clinical and Experimental Reproductive Medicine
• /
• v.50 no.1
• /
• pp.44-52
• /
• 2023

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.