• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1067-1073
• /
• 2003

Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1$\beta$, and nitric oxide (NO) in microglia. In the study, we found that 100 $\mu$ g/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 hand 48 h, compared to the $A\beta$42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as $A\beta$42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1$\beta$ and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in $A\beta$42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1$\beta$ and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive AD peptides in the AD progressing brain.

• Korean Journal of Plant Resources
• /
• v.31 no.4
• /
• pp.303-311
• /
• 2018

In this study, a preliminary evaluation of the antioxidant and anti-inflammatory activity of the Ficus erecta var. sieboldii (Miq.) King (FES) leaf extract has been performed to assess its potential as a natural resource for food and medicinal materials. FES was extracted using 70% EtOH and then fractionated sequentially using n-hexane, $CH_2Cl_2$, EtOAc, and n-BuOH. To screen for antioxidant and anti-inflammatory agents effectively, the inhibitory effect of the FES extracts on the production of oxidant stresses (DPPH, xanthine oxidase, and superoxide) and pro-inflammatory factors (NO, iNOS, COX-2, $PGE_2$, IL-6, and $IL-1{\beta}$) in the murine macrophage cell line RAW 264.7 activated with lipopolysaccharide (LPS) was examined. Among the sequential solvent fractions of FES, the $CH_2Cl_2$ and EtOAc fractions showed decreased production of oxidant stresses (DPPH, xanthine oxidase and superoxide), and the hexane and $CH_2Cl_2$ fractions of FES inhibited the production of pro-inflammatory factors (NO, iNOS, COX-2, and $PGE_2$). The $CH_2Cl_2$ fraction also inhibited the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$). These results suggest that FES has a significant effects on the production of oxidant stresses and pro-inflammatory factors and may be used a natural resource for antioxidant and anti-inflammatory agents.

• BMB Reports
• /
• v.51 no.11
• /
• pp.545-546
• /
• 2018

With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

• Preventive Nutrition and Food Science
• /
• v.18 no.1
• /
• pp.23-29
• /
• 2013

This study was designed to investigate the anti-inflammatory effect of oyster shell extract on the production of pro-inflammatory factors [NO, reactive oxygen species (ROS), nuclear factor-kappa B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2)] and pro-inflammatory cytokines [Interleukin-$1{\beta}$ (IL-$1{\beta}$), Interleukin-6 (IL-6) and TNF-${\alpha}$] in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Cell viability, as measured by the MTT assay, showed that oyster shell extract had no significant cytotoxicity in Raw 264.7 cells. The treatment with oyster shell extract decreased the generation of intracellular reactive oxygen species dose dependently and increased antioxidant enzyme activities, such as SOD, catalase, GSH-px in LPS-stimulated macrophage cells. Oyster shell extract significantly suppressed the production of NO and also decreased the expressions of iNOS, COX-2 and NF-${\kappa}B$. Additionally, oyster shell extract significantly inhibited the production of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-stimulated Raw 264.7 cells. Thus, these results showed that the oyster shell extract had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells.

• Journal of the Korea Convergence Society
• /
• v.8 no.1
• /
• pp.239-243
• /
• 2017

This study aims to demonstrate the inhibitory effect of proinflammatory cytokines by using Frankinsense. The present data was designed to determine the production of the frankincence on pro-inflammatory factors such as $TNF-{\alpha}$ and $IL-1{\beta}$ in lipopolysaccharide(LPS) stimulated RAW264.7 macrophages cell. The cell toxicity was identified by CellTiter 96 AQueous One solution cell proliferation assay. To evaluate of anti-inflammatory effect of frankincence, pro-inflammatory cytokines were measured by ELISA kit. As a result, the frankincence reduced NO and $TNF-{\alpha}$ production without cytotoxicity. As a result, Francincense was not cytotoxic at 10 ug / ml-1000 ug / ml and significantly inhibited the proinflammatory cytokines $TNF-{\alpha}$ and $IL-1{\beta}$. The secretion inhibition effect of proinflammatory cytokine is believed to be applicable to various physiological activity data and functional materials to demonstrate the anti - inflammatory properties of frankincense.

• Biomedical Science Letters
• /
• v.19 no.1
• /
• pp.61-69
• /
• 2013

The aim of this study was to evaluate the effect of exercise-based cardiac rehabilitation on pro- and anti-inflammatory markers in patients with acute coronary syndrome (ACS). ACS patients who underwent percutaneous coronary intervention (PCI) and took medicine during phase II of rehabilitation were recruited for study. Subjects were divided into two groups; exercise group (EX, n=21) and a non-exercise group (non-EX, n=13). Supervised exercise program in hospital consisted of treadmill and bicycle exercise was performed three times per week for 6 weeks. Patients of EX received individual counseling, including knowledge of heart disease, risk factor modification, and physical training. Cardiopulmonary fitness, body composition, and biochemical blood factors were analyzed before and after experiment. There was no significant difference in serum levels of hs-CRP and TGF-${\beta}1$ between groups, and between time intervals. But there was a significant decrease in serum levels of IL-18 (P<.001). And there was a significant increase in ratio of IL-18 to IL-10 (P<.01) and serum levels of IL-10 (P<.001). After cardiac rehabilitation, there was significant increase in exercise duration (P<.001), maximal oxygen uptake ($VO_{2peak}$; P<.001) and decrease in submaximal rate-pressure product (sRPP; P<.05) in EX. In conclusion, exercise-based cardiac rehabilitation during phase II in patients with ACS after PCI decreased serum IL-18 (pro-inflammatory) content and ratio of IL-18 to IL-10 in serum (highly related with disease recurrence), and increased serum IL-10 (anti-inflammatory) content. In addition, it led to improved cardiopulmonary fitness.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3173-3181
• /
• 2015

Background: It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape. Materials and Methods: The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods. Results: The findings indicated that the mutant heterozygous and homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI: 0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as -819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants. Conclusions: We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

• YAKHAK HOEJI
• /
• v.55 no.6
• /
• pp.456-461
• /
• 2011

The aim of the present study is to investigate the anti-inflammatory effect of a Rice Bran Ethanol Extract (RBE). Inflammation, such as a bacterial infection in vivo metabolites, such as external stimuli or internal stimuli to the defense mechanisms of the biological tissue a variety of intracellular regulatory factors deulin inflammatory TNF-${\alpha}$, IL-$1{\beta}$, IL-6, IL-8, such as proinflammatory cytokines, prostagrandin, lysosomal enzyme, free radicals are involved in a variety of mediators. The present study was designed to determine the effect of the RBE on pro-inflammatory factors such as NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 in lipopolysaccharide (LPS) - stimulated RAW264.7 macrophages cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of RBE, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, the RBE reduced NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 production without cytotoxicity. Our results suggest that the RBE may have an anti-inflammatory property through suppressing inflammatory mediator productions and appears to be useful as an anti-inflammatory material.

• Development and Reproduction
• /
• v.21 no.1
• /
• pp.35-46
• /
• 2017

The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

• Korean Journal of Plant Resources
• /
• v.28 no.5
• /
• pp.574-581
• /
• 2015

This study describes a preliminary evaluation of the anti-inflammatory activity of Acrosorium yendoi Yamada extracts. A. yendoi Yamada was extracted using 80% ethanol and then fractionated sequentially with n-hexane, ethyl acetate and butanol. To screen for anti-inflammatory agents effectively, we first examined the inhibitory effect of 80% EtOH extract and solvent fractions of A. yendoi Yamada on the production of pro-inflammatory factors and cytokines stimulated with lipopolysaccharide. In addition, we examined the inhibitory effect of 80% EtOH extract and solvent fractions of A. yendoi Yamada on pro-inflammatory mediators (NO, iNOS, PGE₂, and COX-2) in RAW 264.7 cells. In the sequential fractions of n-hexane and EtOAc inhibited the NO and PGE₂ production and the protein level of iNOS and COX-2, and protein expression of pro-inflammatory cytokines (TNF-α, and IL-6). These results suggest that A. yendoi Yamada may have significant effects on inflammatory factors and may be provided as possible anti-inflammatory therapeutic seaweed.