• BMB Reports
• /
• v.53 no.3
• /
• pp.148-153
• /
• 2020

Erythropoietin and iron have individually shown beneficial effects on early-phase liver regeneration following partial hepatectomy (PHx); however, there are limited data on the combined effect on late-phase liver regeneration after PHx. Here we examined combined effects of recombinant human erythropoietin (rhEPO, 3,000 IU/kg) and iron isomaltoside (IIM, 40 mg/kg) on late-phase liver regeneration following PHx and investigated the possible underlying mechanism. Rats administrated with rhEPO showed significantly higher liver mass restoration, interleukin-6 (IL-6, a hepatocyte mitogen) levels, and Ki-67-positive hepatocytes on day 7 after PHx than saline-treated controls. These beneficial effects were further enhanced on days 7 and 14 by co-treatment with IIM. This combination also significantly improved liver function indices, such as increased albumin production and decreased bilirubin levels, but did not alter serum levels of toxic parameters, such as aspartate transaminase and alanine transaminase. This study demonstrates that the combination of rhEPO and IIM synergistically improves late-phase liver regeneration and function after PHx, probably by promoting IL-6-mediated hepatocyte proliferation without adverse effects. Thus, this combination treatment can be a potential therapeutic strategy for patients undergoing resection for hepatic malignancies.

• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1087-1095
• /
• 2003

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$\beta$ (IL-1$\beta$) and the tumor necrosis factor- $\alpha$ (TNF-$\alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$\alpha$ and IL-1$\beta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $\mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $\mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $\mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $\mu$g/mL with or without LPS. Furthermore, BA (20 $\mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.

• Toxicological Research
• /
• v.26 no.2
• /
• pp.101-108
• /
• 2010

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

• ALGAE
• /
• v.37 no.4
• /
• pp.331-347
• /
• 2022

Atopic dermatitis (AD) is one of major skin inflammatory diseases characterized by excessive Th2-mediated immune responses. Recent evidence provides that interlukin-13 (IL-13) plays the role of a key Th2 cytokine that drives the inflammation underlining AD. Due to adverse effects of commercially available synthetic drugs, the need for treatments based on natural products is gaining much attention. Sargassum horneri is an edible brown algae known for beneficial bioactivities including anti-inflammation. We investigated if polyphenol-rich S. horneri extracts (SHE) could suppress AD-like skin lesions in NC/Nga mice and if that involved inhibition of the infiltration of Th2-mediated cytokine IL-13. We observed markedly increased infiltration of IL-13 positive cells in AD-like skin lesions of mice but SHE treatments decreased it. Also, the dermal expression of IL-13 was sufficient to cause inflammatory responses in mice skin resembling human AD. SHE suppressed the dermal infiltration of inflammatory cells where IL-13 plays a crucial role in skin tissues and in the recruitment of inflammatory cells. Furthermore, it was confirmed that SHE reduced T cell, dendritic cell, and macrophage populations in spleen. Moreover, SHE decreased the collagen deposition in skin and ear dermis resulting in reduced fibrosis that occurs in AD due to excessive collagen. Taken together, our results reveal that SHE suppressed the infiltration of inflammatory cells into skin dermis by decreasing the infiltration of IL-13 positive cells. Therefore, SHE could be taken as a useful therapeutic agent to alleviate AD.

• Applied Chemistry for Engineering
• /
• v.30 no.5
• /
• pp.569-579
• /
• 2019

In this study, the effect anti-oxidant, anti-inflammatory, and liver protective activity was investigated via quick ultrasonic disintegration of pine pollen using a probe sonicator (PS) followed by the extraction with water, 70% ethanol, and 100% ethanol. The anti-inflammatory effect was studied by measuring the production of nitric oxide (NO) and cytokine in RAW264.7 cells induced with lipopolysaccharides (LPS). The cell toxicity was also checked with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the experiment was conducted using non-toxic $100{\mu}g/mL$. The NO inhibition rate was highest in the 70% ethanol PS group at $85.99{\pm}0.12%$. Also an excellent efficiency was obtained from the results of interlukin-1 beta ($IL-1{\beta}$) and tumor necrosis factor alpha ($TNF-{\alpha}$), which is related to inflammation-related cytokine, with the respective inhibition rates of 63 and 22%. To examine liver protective activity, HepG2 cells were treated with Taclin, and the generation of glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH) was measured in the culture solution. From GOT and LDH generation results, the inhibition rates in the 70% ethanol PS group were 28% and 13%, respectively, which was higher compared to that of using negative control group. Our results suggest that pine pollen extracted in 70% ethanol using PS may be used to develop food products that have anti-aging, anti-inflammatory, and liver protective effects.

• Journal of Chest Surgery
• /
• v.33 no.5
• /
• pp.407-418
• /
• 2000

Background: With open heart surgery(OHS), it has been recognized that many postoperative complications and postperfusion syndrome are associated with the activations of complements and leulocytes. Recently, some investigators also demonstrated that interlukin-6(IL-6) linked highly with postperfusion syndrome. The puropose of this study was to investigate the sequential changes of the IL-6 and to clarify each IL-6 relationship to the complements(C3, C4) and inflammatory response following cardiopulmonary bypass(CPB). Material and Method: To determine serum levels of IL-6, complements, leukocytes, and biochemistric markers of liver and renal function, blood samples were taken from th radial artery in 30 adult patients undergoing OHS with CPB. Result: Serum IL-6 levels incrased significantly at 10 minutes after CPB-on(CPB-10) in comparison with the control levels and reached the peak at CPB-off(p<0.05). Serum complement levels declined rapidly at CPB-10 and remained at the lower levels during CPB(p<0.01). Sequential changes of IL-6 levels had positive correlations with the changes of total leukocytes and neutrophil fractions(p<0.05), but had negative correlations with lymphocyte fractions(p<0.05). Changes of C3 related postively to monocyte fractions(p<0.05). Postoperative levels of total protein and albumin, decreased significantly in comparison with the control levels(p<0.01), while the postoperative levels of AST(aspartate transaminase) and bilirubin increased (p<0.01). At CPB-off, IL-6 levels had negative correlations with total protein and albumin levels(r=-0.60, -0.47 respectively, p<0.05), whereas C3 levels had positive correlations with albumin levels(r=0.40, p<0.05). IL-6 levels, as well as neutrophil fractions, had positive correlations with aortic clamp time(ACT) and total bypass time(TBT) (IL-6; r=0.82, 0.79 respectively, neutrophil fractions; r=0.50, 0.56 respectively, p<0.05), wheres lymphocyte frations and albumin levels had negative correlations whith ACT and TBT(lymphocyte fractions; r=-0.52, -0.58 respectively, albumin; r=-0.58, -0.55 respectively, p<0.05). Conclusion: These data showed that elevated production of serum IL-6 during CPB may play a pivotal role in systemic inflammatory responses and prologed CPB period may be assosiated with more sever postperfusion syndromes.

• Journal of Life Science
• /
• v.22 no.6
• /
• pp.744-750
• /
• 2012

The aim of the present study is to investigate the effects of 12 weeks-moderate aerobic exercise training on body composition, adiponectin, retinol-binding protein-4 (RBP-4), and vascular inflammation factors in obese children. The subjects were classified into two groups, one of which was an exercise group (n=15) practicing moderate aerobic exercise training for 12 weeks, and the other group, the control group (n=13), was not in that program. The exercise group participants performed on the treadmill running at heart rate reserve (HRR) 50% of exercise intensity for 300 kcal of the consumed time. The results of all the studies and inspections are as follows: Weight, body mass index, body fat, and systolic and diastolic blood pressure were significantly lower, while $VO_2$ max was higher in the exercise group than in the control group (p<0.05, respectively). Fasting glucose, insulin, and HOMA-IR levels in the exercise group were significantly decreased (p<0.05), whereas adiponectin levels in the exercise group were significantly increased after 12 weeks' exercise training (p<0.05). In addition, our results showed that RBP4, C-reactive protein (CRP), and interleukin-6 (IL-6) concentrations in the exercise group were significantly lower than those of the control group (p<0.05). This investigation has shown that a 12 weeks-regular aerobic exercise program offers useful effects such as an amelioration of inflammation and body indices in obese children.

• Nutrition Research and Practice
• /
• v.4 no.2
• /
• pp.99-105
• /
• 2010

Obesity is considered a mild inflammatory state, and the secretion of inflammation-related cytokines rises as adipose tissue expands. Inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interlukin 6 (IL-6) and monocyte-chemoattractant protein 1 (MCP-1), are modulated by adipose tissue and known to play an important role in insulin resistance which is the common characteristics of obesity related disorders. In this study we analyzed the effects of Sasa borealis leaves extract on inflammatory cytokines and insulin resistance in diet induced obese C57/BL6J mice. The obese state was induced by a high fat diet for 20 weeks and then the mice were divided into two groups; obese control group (OBC, n = 7) and experimental group (OB-SBE, n = 7). The OBC group was fed a high fat diet and the OB-SBE group was fed a high fat diet containing 5% Sasa borealis leaves extract (SBE) for 12 weeks. We also used mice fed a standard diet as a normal control (NC, n = 7). The body weight and adipose tissue weight in the OB group were significantly higher than those in the NC group. The effects of the high fat diet were reduced by SBE treatments, and the body weight and adipose tissue deposition in the OB-SBE group were significantly decreased compared to the OBC group. The OBC group showed higher serum glucose and insulin levels which resulted in a significant increase of incremental area under the curve (IAUC) and HOMA-IR than the NC group. Also, serum leptin, TNF-${\alpha}$, and IL-6 levels were significantly higher in the OBC group than in the NC group. In contrast, the OB-SBE group showed a reversal in the metabolic defects, including a decrease in glucose, insulin, IAUC, HOMA-IR, TNF-${\alpha}$, IL-6 and leptin levels. These results suggest that BSE can suppress increased weight gain and/or fat deposition induced by a high fat diet and theses effects are accompanied by modulation of the inflammatory cytokines, TNF-${\alpha}$ and IL-6 secretion resulting in improved insulin resistance.

• Food Science and Preservation
• /
• v.24 no.8
• /
• pp.1122-1128
• /
• 2017

Pumpkin has long been used as traditional health materials in oriental medicine, pharmacy, medicine, and food industries in many countries. In this study, the water extract and two active components from tendril of young C. moschata Duch. were investigated on inflammation inhibitory activity. The water extract of young C. moschata Duch. showed high cell viability over 95% and it decreased the production of interlukin 6 (IL-6) and tumor necrosis factor (TNF-${\alpha}$) in the capacity of mouse bone marrow-derived macrophages (BMDM) upon lipopolysaccharide (LPS) stimulation. Also, isolated fraction (B4) suppressed the secretion of IL-6 and TNF-${\alpha}$. Among the domestically cultivated pumpkins, B4 fraction contained in the tendril part of them and it comprised of the order of tendril from Cucurbita pepo var. cylindrica, old of C. moschata Duch., and young of C. moschata Duch. These results suggest that water extracts of C. moschata Duch. and purified active compound, rutin, show anti-inflammation activity by suppression of the secretion of IL-6 and TNF-${\alpha}$. It can be applicable as pharmaceutical materials.

• The Korean Journal of Mycology
• /
• v.38 no.2
• /
• pp.179-183
• /
• 2010

This study is to characterize the postulated anti-inflammatory effect of the hot water extracts from the Phellinus baumii. RAW264.7, macrophage cell line, was activated by lipopolysaccharide (LPS) and, further, treated with Phellinus baumii's aqueous extract. When the cultured macrophage cells were treated with LPS, they show typical signs of endoplasmic reticulum stress (ERS) and an increment in secretion of inflammatory cytokine compared to the non-treated control: The expression of glucose-regulated protein78 (Grp78), Grp94, and C/EBP homologous protein/GADD 153 (CHOP) increased along with augmented secretion of interlukin-6. Cellular nitric oxide content also significantly went up in comparison to the non-LPS treatment. When the LPS-treated RAW264.7 was treated with the aqueous Phellinus baumii extracts, however, the expression of ERS markers markedly reduced and the release of nitric oxide declined. Also, the expression of induced nitric oxide synthase (iNOS) notably diminished similarly as the NO content. In conclusion, this study strongly indicated that aqueous Phellinus baumii extract can be utilized directly as anti-inflammation agent and serves as a source of functional ingredient to lessen the inflammation.