• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.442-448
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• 2015

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-$1{\beta}$-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.70-74
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• 2013

L-ascorbic acid (vitamin C) is one of the well-known antiviral agents, especially to influenza virus. Since the in vivo antiviral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-${\alpha}/{\beta}$, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-${\alpha}/{\beta}$, were increased in the lung. Taken together, vitamin C shows in vivo antiviral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-${\alpha}/{\beta}$.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.628-647
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• 2018

Purpose: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. Methods: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin $(IL)-1{\beta}$, -4, -5, -6, -13, and tumor necrosis factor $(TNF)-{\alpha}$, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. Results: Body composition, asthma control, and the levels of $IL-1{\beta}$, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. Conclusions: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

• Korean Journal of Medicinal Crop Science
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• v.27 no.4
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• pp.247-258
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• 2019

Background: Astragali radix (A) and Lithospermi radix (L) have long been used as traditional medicines due to their known anti-inflammatory effects. This study aimed at evaluating, their optimal mixing ratio and their functional compounds by investigating the inhibitory effects of mixed extracts of A and L and their active compounds on matrix metalloproteinases (MMPs). Methods and Results: A and L extracts were obtained by extraction at $80^{\circ}C$ using 50% and 70% fermented alcohol, respectively, and then mixed at a ratio of 5 : 5, 6 : 4, 7 : 3 and 8 : 2 (w/w). The activities of MMP-1, MMP-3, and MMP-13 were evaluated in interleukin-1beta ($IL-1{\beta}$)-induced SW1353 cells. The extract mixtures showed synergistic inhibitory effects on MMP-3 and MMP-13, higher than the effects of the individual A and L extracts. The 7 : 3 mixture (ALM16) showed the most effective MMPs inhibitory activity, while among the active ingredients, calycosin-7-O-${\beta}$-D-glucoside and lithospermic acid exhibited excellent MMPs inhibitory activity. Additionally, an HPLC method was established for simultaneous quantification of the effective components of the extract mixtures, and validated by measuring the linearity, precision and accuracy of the limit of detection (LOD) and limit of quantification (LOQ). Conclusions: ALM16 showed the most effective MMPs inhibitory activity. Calycosin-O-${\beta}$-D-glucoside, calycosin and lithospermic acid were identified as useful candidates, as they were the major functional compounds in the MMP inhibitory activity. Summarily, ALM16 might be a highly effective in osteoarthritis management, owing to its because it exhibits a protective effect on cartilage via excellent inhibition of MMPs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.217-222
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• 2014

Lonicerae Flos containing formulation, Geumeumyoungji-tang (GYT), is an herbal prescription prepared using 5 different herbal drugs, namely, Lonicerae Flos, Ganoderma, Lactucae Herba, Xanthii Fructus, and Smilacis Rhizoma. This study was focused on the investigation of the pharmacological effects of GYT on allergic reactions. As the first step of the study, GYT was administered BALB/c mice which were sensitized by 2,4-dinitrofluorobenzene (DNFB). As the result GYT ameliorated dermatitis provoked by DNFB. The serum IgE level of the DNFB sensitized-mouse was significantly decreased when GYT was administered. In order to confirm the moderating effect of this prescription on allergic reaction, GYT was pretreated to human mast cells (HMC-1) before they were stimulated by phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI). GYT suppressed secretion of inflammatory cytokines, interleukin (IL)-6 and IL-8, from HMC-1. Additionally, pretreatment of GYT showed regulating effect on COX-2 expression. Collectively, these findings provide insights into the pharmacological actions of GYT as a potential agent for treatment of allergic dermatitis.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.39-44
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• 2008

Objectives: Notopterygium incisum(N. incisum) and Saposhnikovia divaricata(S. divaricata) have been clinically used in traditional oriental medicine for treatment of inflammatory diseases. Also, a herbal mixture prepared with N. incisum and S. divaricata has been strongly linked to the anti-inflammatory effect. In this study, we evaluate the synergistic anti-inflammatory effect of N. incisum and S. divaricata. Methods: For evaluating the anti-inflammatory activity of a herbal mixture of N. incisum and S. divaricata in vivo, we measured the changed ear thickness in 12-O-tetradecanoyl-phorbol-13-acetate(TPA)-induced mouse ear edema model after topical application of herbal mixture. In addition, the levels of markers for inflammation, such as tumore necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$, and nitric oxide(NO), were determined by ELISA assay in lipopolysaccharide-stimulated Raw 264.7 cells. Results: We reported that water extracts of N. incisum and S. divaricata combination significantly inhibited the mouse ear edema induced by TPA. Moreover, the water extracts of N. incisum and S. divaricata combination exhibited synergistic effects in down-regulating IL-1${\beta}$ level, but not TNF-${\alpha}$ and NO. Conclusions: These results suggest that combined treatment of N. incisum and S. divaricata, based on seven methods in prescription compatibility, has a synergistic effect in down-regulating inflammatory response both in vivo and in vitro models. Especially, it seems that IL-1${\beta}$ is a one of main target of the mixture of N. incisum and S. divaricata on anti-inflammatory activity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.82-93
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• 2008

Objective: Previously, the methanol extracts of the semen of Xanthium strumsrium could involved anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated Raw 264,7 cells, We evaluated the anti-allergic effects of X. strumarium on rat basophilic leukemia (RBL-2H3) cells, Methodes : To investigate the effect of X. strumarium on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced RBL-2H3 cells. The effects of X. strumarium on the degranulation and the pro-inflammatory cytokines secretion and expression from RBL-2H3 cells were evaluated with $\beta$-hexosaminidase assay, ELISA, and RT-PCR analysis, In addition, we examined the effects of X. strumarium on nuclear factor (NF)-${\kappa}B$ activation and $I{\kappa}B-\alpha$ degradation using Western blot analysis. Results : X. strumarium inhibited degranulation and secretions and expressions of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-\alpha$), interleukin (IL)-4 and cyclooxygenase (COX)-2, on stimulated RBL-2H3 cells, however, X. strumarium not affect cell viability. In stimulated RBL-2H3 cells, the protein expression level of nuclear factor-kappa B (NF-${\kappa}B$) was decreased in the nucleus by X. strumarium. In addition, X. strumarium suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein in RBL-2H3 cells. Conclusion : These results suggest that X. strumarium inhibits the degranulation and secretion of pro-inflammatory cytokines through blockade of NF-${\kappa}B$ activation and I $I{\kappa}B-{\alpha}$ degradation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1572-1578
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• 2008

In previous report, Seungmagalgeun-tang (SGT) could exert its anti-inflammatory actions in the BV-2 microglial cells. However, study on the anti-inflammatory effect of SGT in mast cells has not been identified. Therefore, we examined on the anti-inflammatory effect of SGT on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced rat basophilic leukemia (RBL-2H3) cells. SGT inhibited the release of ${\beta}$-hexosaminidase and secretion and expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-4 on RBL-2H3 cells, without affecting cell viability. The protein expression level of nuclear factor (NF)-${\kappa}B$ (p65) was decreased in the nucleus by SGT. In addition, SGT suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein, the activation of p38 mitogen-activated protein kinase (MAPK), and the expressions of cyclooxygenase (COX)-2 mRNA and protein level in RBL-2H3 cells. These results suggest that SGT could be involved anti-allergic effect by control of NF-${\kappa}B$ (p65) translocation into the nucleus through inhibition of $I{\kappa}B-{\alpha}$ degradation and suppression of COX-2 expression.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.174-180
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• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• Journal of Microbiology and Biotechnology
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• v.24 no.1
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• pp.127-131
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• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.