• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4609-4614
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• 2016

Purpose: To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methods: In the present block randomized, placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum interleukin-6 (IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), vascular endothelial growth factor (VEGF) and copper levels were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning, middle and end of the study. Results: The patients had a mean age and Karnofsky Performance Scale of 43.7 years and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group were also significantly reduced compared to the placebo group and $TNF-{\alpha}$ increased less. Conclusions: It seems that reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors such as VEGF, IL-6 and $TNF-{\alpha}$. Approaches targeting angiogenesis may improve survival and can be used as a future therapeutic strategy.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.71-80
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• 2008

Objective: There is increasing evidence that chronic non-bacterial prostatitis is recognized to be a local inflammatory disease, and there is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and clinical value in the evaluation of therapeutic efficacy. Prunella vulgaris has been traditionally used in treatment of inflammatory diseases, including of scrofula, goiter, and allergy diseases. In this study, we investigated the effects of Prunella vulgaris on inflammatory cytokines and cytopathological alternation in the rat model of non-bacterial prostatitis induced by castration and $17{\beta}-estradiol$ treatment. Methods: Two-month-old rats were treated with $17{\beta}-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Prunella vulgaris as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathological parameters including the epithelial score and epithelial-stromal ratio for glandular damage, and the expression of inflammatory cytokine genes including the interleukin $(IL)-1{\beta}$, IL-5, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Prunella vulgaris showed a diminished range of tissue damage. Epithelial score was improved in Prunella vulgaris over that of the control (P<0.05). The epithelial-stromal ratio was lower with Prunella vulgaris when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytokine genes, Prunella vulgaris inhibited the expression of $IL-1{\beta}$ and $TNF-{\alpha}$ genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions: These findings suggest that Prunella vulgaris may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and promotion of anti-inflammatory cytokine. From theses results, we suggest that Prunella vulgaris could be a useful remedy agent for treating chronic non-bacterial prostatitis.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.206-217
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• 2023

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-β were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-β) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.855-869
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• 2023

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

• Korean Journal of Medicinal Crop Science
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• v.17 no.2
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• pp.90-96
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• 2009

The objective of this study was to investigate the effect of crude ginseng total saponins (CGS) against airway inflammation (AI) and airway hyperresponsiveness (AH) induced by diesel exhaust particles (DEP) in mice. AI and AH were induced by the intratracheal instillation with 0.1 $mg/m{\ell}$ of DEP suspension once a week for 10 weeks combined with ovalbumin (OVA) sensitization. Mice were also treated orally with 75 $mg/m{\ell}$ of CGS, 5 days a week for 10 weeks. Oral CGS treatment decreased in the level of serum immunoglobulin (IgE) and histamine increased by DEP and OVA, and declined respiratory resistance. It also dropped an enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, and an increased T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that CGS may alleviate allergen-related AI and AH in mice and may play an important role in the modulation of asthmatic inflammation.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.947-952
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• 2008

The unripe fruit of Momordica charantia (MC) has been shown to possess antidiabetic activity. However, the mechanism of its antidiabetic action has not been fully understood. In this study, the effects of the aqueous ethanolic extract of MC (AEE-MC) were evaluated on the apoptosis in pancreatic $\beta$-cells treated with a combination of the cytokines, interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-$\alpha$, and interferon (IFN)-$\gamma$. In MIN6N8 cells, the inhibitory effect of AEE-MC was significantly observed at 2 to 50 ${\mu}g/mL$: a 26.2 to 55.6% decrease of cytoplasmic DNA fragments quantified by an immunoassay. The molecular mechanisms, by which AEE-MC inhibited $\beta$-cell apoptosis, appeared to involve the inhibition on the expression of p21, Bax, and Bad, the up-regulation of Bcl-2 and Bcl-$X_L$, and the inhibition on the cleavage of caspase-9, -7, and -3 and poly (ADP-ribose) polymerase. This study suggests that MC may inhibit cytokine-induced apoptosis in $\beta$-cells and, thus, may contribute via this action to the antidiabetic influence in diabetes.

• Journal of Dairy Science and Biotechnology
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• v.41 no.1
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• pp.34-43
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• 2023

Hydrolysis of whey-derived proteins using lactic acid bacteria (LAB) utilizes the mass culture method and fermentation of LAB to produce effective bioactive peptides. Whey protein has the biological potential of its precursors, but the active fragments may not be released depending on the hydrolysis method. As an alternative to these problems, the nutritional and bioactive functionality of the hydrolysis method have been reported to be improved using LAB for whey protein. Peptide fractions were obtained using a sample fast protein liquid chromatography device. Antioxidant activity was verified for each of the five fractions obtained. In vitro cell experiments showed no cytotoxicity and inhibited nitric oxide production. Cytokine (IL [interleukin]-1α, IL-6, tumor necrosis factor-α) production was significantly lower than that of lipopolysaccharides (+). As a result of checking the amino acid content ratio of the fractions selected through the AccQ-Tag system, 17 types of amino acids were identified, and the content of isoleucine, an essential amino acid, was the highest. These properties show their applicability for the production of functional products utilizing dietary supplements and milk. It can be presented as an efficient method in terms of product functionality in the production of uniform-quality whey-derived peptides.

• Journal of Microbiology and Biotechnology
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• v.33 no.6
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• pp.823-830
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• 2023

Lactococcus lactis is a lactic acid bacterium and used in the dairy food industry. The ameliorating effects of Lactobacillus species on atopic dermatitis (AD) have been extensively studied, but the specific effect of L. lactis strains has not yet been investigated. In this study, the efficacy of L. lactis LB 1022, isolated from natural cheese, was evaluated using RAW 264.7, HMC-1 and HaCaT cell lines and an ovalbumin-sensitized AD mouse model. L. lactis LB 1022 exhibited nitric oxide suppression and anti-allergy and anti-inflammatory activity in vitro. Oral administration of L. lactis LB 1022 to AD mice significantly reduced the levels of IgE, mast cells, and eosinophils, and a range of T cell-mediated T helper Th1, Th2, and Th17-type cytokines under interleukin (IL)-10, transforming growth factor-β (TGF-β), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP). In addition, L. lactis LB 1022 treatment increased the concentration of short-chain fatty acids. Overall, L. lactis LB 1022 significantly modulated AD-like symptoms by altering metabolites and the immune response, illustrating its potential as candidate for use in functional food supplements to alleviate AD.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.4
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• pp.214-223
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• 2017

Objective: In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. Methods: This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. Results: Before seminal plasma exposure, the expression levels of T-bet (p< 0.007), $interferon-{\gamma}$ (p= 0.013), and tumor necrosis factor $(TNF)-{\alpha}$ (p= 0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p< 0.001), Foxp3 (p= 0.001), and interleukin (IL)-35 (p< 0.003) were lower. After seminal exposure, the expression of T-bet (p= 0.02), Rorc (p< 0.001), $TNF-{\alpha}$ (p= 0.001), Foxp3 (p= 0.02), and $interferon-{\gamma}$ (p= 0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p= 0.02), Rorc (p< 0.001), IL-23 (p= 0.04), IL-17 (p= 0.02), IL-6 (p< 0.001), transforming growth $factor-{\beta}$ (p= 0.01), and IL-35 (p< 0.001) increased in the successful IVF group. Conclusion: In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.17-26
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• 2022

Objective : The aim of the present study is to examine hepatic lipid-lowering and anti-inflammatory effects of silymarin combined with Jakyakgamcho-tang on non-alcoholic fatty liver disease in a high fat diet-induced obese mice model. Methods : C57BL/6 mice were divided into four dietary groups: (1) Normal, (2) Control (60% high-fat diet), (3) Control + silymarin 50 mg/kg/day (Silymarin), (4) Control + Silymarin 50 mg/kg/day + Jakyakgamcho-tang 100 mg/kg/day (SPG). After 12 weeks administration, mice were sacrificed and lipids and inflammation-related biomarkers were analyzed liver and plasma. Results : Silymarin and SPG treatments significantly lowered body and liver weights compared to the Control. Serumlipids (triglyceride (TG), total cholesterol) and pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1𝛽, and IL-6) concentrations were significantly lowered in the Silymarin and SPG groups than the Control group. Silymarin and SPG treatments suppressed hepatic TG level and hepatic lipid droplets compared to the Control. Theses two treatments significantly increased hepatic kinase B1 and AMP-activated protein kinase protein levels, and significantly decreased hepatic key lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase and stearyl coenzyme A desaturase 1) protein levels than the Control. SPG also significantly increased hepatic fatty acid oxidation-related protein (peroxisome proliferator-activated receptor alpha and uncoupling protein 2) levels than the Control. Conclusions: Silymarin and SPG suppressed hepatic lipid accumulation by regulating hepatic protein expression, and lowered blood pro-inflammatory cytokines concentrations though the synergic effect of silymarin and Jakyakgamchotang was not clear.