• The Korean Journal of Food And Nutrition
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• v.36 no.6
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• pp.436-444
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• 2023

To produce an intestinal immunomodulatory beverage containing Centella asiatica extract (CAE), three types of CAE-added beverage prototypes were prepared, and their immunomodulatory activities and marker compounds were analyzed. As a result of the cytotoxicity assessment, all the beverages did not show significant toxicity compared to the control group. Next, the immunomodulatory activities of the beverage prototype were evaluated using the inflammatory model of IL-1β-induced intestinal epithelial cell line. All the samples significantly reduced the production of IL-6, IL-8, and MCP-1 in a CAE concentration-dependent manner. In addition, CAE-added beverages inhibited NO, IL-6, and IL-12 production in LPS-induced RAW 264.7 cells. When the major triterpenoids, as marker compounds for the production of CAE-added beverages, were analyzed by HPLC-DAD, only asiaticoside was detected beyond the limit of quantification, while madecassoside, madecassic acid, and asiatic acid were not detected. The amounts of asiaticoside in CAE-added beverage prototypes were confirmed in No. 1 (19.39 ㎍/mL), 2 (19.25 ㎍/mL), and 3 (19.98 ㎍/mL). In conclusion, the results of this study suggested that CAE-added beverage prototypes induced immunomodulatory effects in the intestinal inflammatory cell line models and asiaticoside could be used as a marker compound for CAE-added beverage production.

• Journal of Nutrition and Health
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• v.56 no.3
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• pp.231-246
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• 2023

Purpose: The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods: Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. Results: Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. Conclusion: These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.45-63
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• 2011

Objective : Atractyloides Chinensis Rhizome (ACR) is widely used in oriental medicine as a remedy for an inflammation and an allergic disease. However, as yet there is no clear explanation of how ACR affects the production of inflammatory cytokine. This study was to determine the effects of ACR on the mast cell-mediated inflammatory responses. Method : The amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of ACR was measured. The TNF-${\alpha}$ protein levels were analysised by Western blots. The TNF-${\alpha}$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-${\alpha}$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. NF-${\kappa}$B, phospho-I${\kappa}$B and MAPKs were examined by Western blot analysis. The NF-${\kappa}$B promoter activity was examined by a luciferase assay. Results : 1. The expressions of TNF-${\alpha}$ and TNF-${\alpha}$ mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 2. The expressions of IL-6 and IL-6 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 3. The expressions of IL-8 and IL-8 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$ specially. 4. The expressions of Phosphorylated-JNK were decreased, not p38, ERK 5. The expressions of NF-${\kappa}$B were decreased dose-dependently at 0.1-0.2mg/$m\ell$ of ACR. The expressions of Phosphorylated I${\kappa}$B were significantly decreased at 0.2mg/$m\ell$. In addition, ACR suppressed PMA plus A23187-induced NF-${\kappa}$B promoting activity. Conclusion : It is suggested that ACR should suppress through inhibition of NF-${\kappa}$B activity and cytokine production.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.2
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• pp.1-15
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• 2021

Objectives: This study was designed to examine immuno-modulatory effects of Evodia Rutaecarpine by activating innate immune system and inhibiting inflammation. Methods: First, Cell cytotoxicity was examined with 4T1 breast carcinoma and TG-induced macrophage. To investigate activating innate immune system of Evodiamine Rutacarpine Extract (ERE) on macrophage, we tested tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with ERE to observe innate immune modulating effect of ERE on RAW 264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In cytotoxicity analysis, ERE significantly affected tumor cell growth above specific concentration. Also, ERE significantly affected macrophage growth above specific concetration. As compared with the control group, the production of TNF-α, IL-12 and IL-6 were increased in TG-induced macrophage. As compared with the control group, TNF-α and IL-6 were significantly up-regulated in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating ERE was significantly decreased compared with control group. In addition, We observed ERE inhibited the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38 in western blotting by treating ERE on RAW 264.7 cell. Conclusions: ERE seems to have considerable impact on the anti-cancer effect by activation of innate immune system and inflammation control.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.11 no.1
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• pp.58-73
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• 2005

Objectives : This study was to investigate the effect of Kagammokbanggi-tang on the Freund's Complete Adjuvant(FCA)-induced arthritis in rats. Methods : Arthritis was induced by intradermal injection of FCA into base of tail. Arthritic rats were divided into control(n=10) and sample(n=10) group. Control group was taken normal saline for twenty days and sample group was taken extracts of Kagammokbanggi-tang for same duration. Normal group(n=10), non-arthritic group, was injected with mineral oil and was taken normal saline for twenty days. Body weight, paw edema volume and ankle joint thickness were measured at 0, 10, 15, 20 days after treatment. $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, $PGE_2$ in synovia were analysed by ELISA at 20 days after treatment. Histochemical investigation of NADPH-d in the PAG and histopathological study on the ankle joint were performed at 20 days after treatment. Results : Paw edema volume, ankle joint thickness, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, $PGE_2$, NADPH-d of sample group were significantly decreased compared with control group. Conclusions : These results indicated that Kagammokbanggi-tang has antiarthritic and analgesic effects, and inhibited expression of NOS on the progression of FCA- induced arthritis in rats.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.59-69
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• 2022

Purpose: Natural medicinal plant extracts have recently attracted attention as health beneficial foods and potential therapeutic agents for prevention of various diseases. This study was undertaken to measure the anti-inflammatory effect of the ethanol-water fraction obtained from the above-ground portion of Spiraea prunifolia var. simpliciflora, a wild-growing plant in Korea. The final fraction used in this study was the H₂O-EtOH (40:60) fraction (SP60), which had the highest antioxidant activity, as determined in previous studies. Methods: The amounts of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β production were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells exposed to SP60. Western blot was performed to measure the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and the activation of nuclear factor (NF)-κB. Results: SP60 exerted no cytotoxicity up to concentrations of 125 ㎍/mL. The levels of inflammatory cytokines, such as NO, TNF-α, IL-6, and IL-1β, were significantly decreased in LPS-stimulated RAW264.7 cells exposed to SP60. In addition, the expression levels of iNOS, COX-2, and phosphorylated p65 showed a concentration-dependent decrease subsequent to SP60 treatment. These results indicate that SP60 inhibits the LPS-induced production of inflammatory cytokines, iNOS, and COX-2, by inhibiting the activation of NF-κB, which is responsible for the expression of inflammatory mediators. Conclusion: The results presented in this study indicate that the H₂O-EtOH (40:60) fraction (SP60) extracted from the above-ground portion of Spiraea prunifolia var. simpliciflora has the potential to be developed as a medicine or healthcare food and functional material possessing anti-inflammatory effects. However, it is necessary to first confirm the anti-inflammatory effects of SP60 in in vivo models.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.105-112
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• 2007

Background: Oxidative stress may play an important role in the pathogenesis of endotoxin-induced acute lung injury (ALI). This study evaluated the therapeutic effect of ${\alpha}$-lipoic acid, a nonenzymatic antioxidant, in a rat model of lipopolysaccharide (LPS) induced ALI. Materials and Methods: ALI was induced in Sprague-Dawley rats by instilling LPS (E.coli, 3mg/Kg) into the trachea. The rats were classified into the control, control+${\alpha}$-lipoic acid, LPS, and LPS+${\alpha}$-lipoic acid groups.The lung lavage neutrophil count, cytokine-induced neutrophil chemoattractant (CINC), lung myeloperoxidase (MPO), and cytokine concentrations (TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and IL-10) were measured at 2 h and 6 h after LPS administration. Results: The total cell and neutrophil counts of the LPS+${\alpha}$-lipoic acid groups were significantly lower than the LPS groups. The protein concentration in the BAL fluid was similar in the LPS groups and LPS+${\alpha}$-lipoic acid groups. The TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 concentrations in the BAL fluid were not decreased by the ${\alpha}$-lipoic acid treatment in the LPS treated rats. Conclusions: Although ${\alpha}$-lipoic acid decreased the level of LPS-induced neutrophil infiltration into the lung, it could not attenuate the LPS-induced ALI at the dose administered in this study.

• The Journal of Dong Guk Oriental Medicine
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• v.6 no.2
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• pp.99-107
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• 1998

Cyclosporin A(CsA) is a selective immunosuppressive agent that has been credited with improved survival of solid organ allografts. Lymph node of BALB/C mouse administered CsA immunohistochemically observed to understand immunosuppressive effects of CsA on T lymphocytes, IL-2 receptors, and natural killer NK cells in lymph node. CsA orally administered daily for 10days at the dose 45mg/kg/day/. The lymph node were obtained at day 3, 7, and 14 after CsA administration and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25), and NK-1.1(CD56). There were little changes of reactive degree and number of helper T lymphocytes, cytotoxic T lymphocytes, IL-2 receptors, and NK cells at day 3 after CsA administration, but they began to decrease at day 7. These decrease were greatest at day 14. The helper T lymphocytes. cytotoxic T lymphocytes, IL-2 receptors, and NK cells distributed in paracortex and medullary sinus. These results indicated that the secretion of IL-2 began to decrease at day 7 after CsA administration and subsequently to suppress T lymphocytes and NK cell as components of cell-mediated immunity.