• The Korea Journal of Herbology
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• v.35 no.1
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• pp.35-44
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• 2020

Objectives : The objective of this study was to investigate the therapeutic effect of Corni Fructus 30% ethanol extract (CFE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal group (N, n=10), MIA-induced osteoarthritis control group (Con, n=10), indomethacin 5 mg/kg treated group (INDO, n=10), CFE 200 mg/kg treated group (CFE, n=10). Blood and articulation tissues were collected after two weeks of drug administration. Oxidative stress was analyzed with reactive oxygen species (ROS), peroxynitrite (ONOO-). And the Nuclear factor erythroid-2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), Nuclear Factor Kappa B p65 (NF-κBp65), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), Interleukin 1β (IL-1β), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot. Results : The administration of CFE showed a significant reduction of changes in relative hind paw weight distribution. Reactive oxygen species (ROS) and peroxy nitrite (ONOO-) levels of articulation tissues were significantly decreased in CFE compared to the control group. Western blot measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2 showed that the CFE group was increased compared to the Con group. And western blot measurements of NF-κBp65, COX-2, iNOS, TNFα, IL-6, IL-1β showed that the CFE group was reduced compared to the Con group. Also CFE group decreased MMP-1 and increased TIMP-1. Conclusion : Based on the above results, it can be seen that osteoarthritis is improved when Corni Fructus 30% ethanol extract treated.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.166-182
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• 2022

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.9-18
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• 2022

Objectives This study was conducted to confirm the anti-inflammatory effect of Naetakbaekryeom-san (NTB), and whether it could be another treatment for inflammatory diseases. Methods The NTB water extract was extracted with hot water at 100℃ for 2 hours, concentrated at 80℃ under reduced pressure, and used. After 2 hours of pretreatment with NTB and positive control Bay11-7082, nitric oxide (NO), inducible NO synthase (iNOS), interleukin (IL)-6, IL-1𝛽, tumor necrosis factor alpha (TNF-𝛼) were measured in RAW264.7 cells activated with lipopolysaccharides (LPS) 500 ng/mL. After 2 hours of pretreatment with NTB, the anti-inflammatory effect of NTB was evaluated by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B) in RAW264.7 cells and 293T cells activated with phorbol 12-myristate 13-acetic acid (PMA) 30 ng/mL. Results In RAW264.7 cells activated with LPS, NTB at concentrations of 0.1, 0.3, and 1.0 mg/mL showed no cytotoxicity, significantly inhibited NO production and inhibition of iNOS expression. TNF-𝛼 cytokine levels was not regulated, but NTB at each concentration inhibited the production of IL-1𝛽 and IL-6, and the effect was higher than that of the positive control Bay11-7082 (20 𝜇M). In PMA-activated RAW264.7 cells and 293T cells, each concentration of NBT decreased the NF-𝜅B transcriptional activity, with the greatest decrease at 1 mg/mL. Conclusions These results demonstrated the anti-inflammatory effect of NTB water extracts, but further studies such as comparison of anti-inflammatory effects and antioxidant effects by NTB component, comparison of effects according to extraction solvents, and clinical studies are needed.

• Journal of Life Science
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• v.33 no.5
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• pp.397-405
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• 2023

Although glutathione (GSH) has been shown to play an important role in the prevention of oxidative damage as an antioxidant, studies on immune regulation by it have not been properly conducted. In this study, we investigated whether luthione^®, a reduced GSH, has an immune enhancing effect in murine macrophage RAW 264.7 cells. The results of flow cytometry and immunofluorescence experiments indicated that luthione increased phagocytic activity, a representative function of macrophages, compared to the control cells. According to the results of the cytokine array, the expression of interleukin (IL)-5, IL-1β, and IL-27 was significantly increased in the luthione-treated cells. Luthione also enhanced the production of tumor necrosis factor-α and IL-1β through increased expression of their proteins, and increased release of the immune mediators such as nitric oxide (NO) and prostaglandin E₂ was associated with increased expression of inducible NO synthase and cyclooxygenase-2. In addition, the expression of cluster of differentiation 86, an M1 macrophage marker, was dramatically enhanced in RAW 264.7 cells treated with luthione. Furthermore, as a result of heat map analysis, we found that cytokine signaling 1/3-mediated signal transducer and activator of transcription/Janus tyrosine kinase signaling pathway was involved in the immunomodulatory effect by luthione. In conclusion, our data suggested that luthione could act as a molecular regulator in M1 macrophage polarization and enhance immune capacity by promoting macrophage phagocytic function.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.2
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• pp.1-18
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• 2023

Objectives The purpose of this study was to evaluate the antioxidant, anti-inflammatory and wound healing effects of Samul-tang-ga-dansam water extract (SD) in wound-induced mice. Methods The mice were divided into five groups (n=7): the normal group, the control group, the positive control group, the low-dose SD group and the high-dose SD group. The normal group had no wounds and the other groups were wounded on the back with a leather punch. Distilled water was administered to the control group, 200 mg/kg of vitamin E was administered to the positive control group. In the low-dose SD group and the high-dose SD group, 1.23 g/kg and 2.47 g/kg of SD were administered, respectively. Antioxidant and anti-inflammatory protein levels were evaluated using western blot analysis. Skin tissue was analyzed by H&E, Masson's trichrome staining method. Results Oral administration of the SD significantly reduced the visible skin damage and decreased the reactive oxygen species and ONOO^- activity of the serum. It significantly increased heme oxygenase-1, superoxide dismutase, catalase, GPx-1/2, Nrf2 and Keap-1 which are antioxidant-related factors in skin tissue and reduced NF-κB p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor α, interleukin (IL)-1β, IL-6 which are inflammation-related factors. Also, SD significantly decreased NOX2, p22^phox and p47^phox and increased α-smooth muscle actin and COL1A1 protein expression in fibroblasts involved in connective tissue repair. According to histological examination, the thickened epithelial layer was thinned and collagen fibers were increased to accelerate wound healing. Conclusions It is suggested that Samul-tang-ga-dansam has antioxidant and anti-inflammatory effects and promotes wound tissue repair.

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.1
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• pp.1-11
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• 2023

In the present study, the antioxidant and anti-inflammatory activities of ethanolic extracts from Lathyrus japonicus at concentrations of 50, 100, and 200 ㎍/mL were investigated in LPS-stimulated, RAW264.7 cells. Antioxidant properties were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power assay. In addition, the production of reactive oxygen species (ROS) was measured using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe by flow cytometry. To examine the anti-inflammatory activity of the extracts of L. japonicus, their effects on the levels of nitric oxide (NO); production of cytokines such as interleukin (IL)-1β, IL-10, and tumor necrosis factor-α (TNF-α); and the activities of enzymes such as inducible NOS (iNOS) and cyclooxygenase-2 (COX-2) were assessed. The IC₅₀ values of the DPPH and ABTS radical scavenging assays were 476.09 ± 1.50 and 34.91 ± 0.37 ㎍/mL, respectively. In addition, L. japonicus extracts not only inhibited ROS production, but also the production of NO, IL-1β, and IL-10, and the activity of iNOS in a dose-dependent manner. In summary, the ethanolic extracts of L. japonicus could be used as a functional food additive and an anti-inflammatory agent owing to their antioxidant and anti-inflammatory activities

• 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.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Korean Journal of Acupuncture
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• v.41 no.2
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.