• 생약학회지
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• 제34권3호통권134호
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• pp.228-232
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• 2003

For effective management of atopic dermatitis, it is important to introduce a therapeutic agent although having the fewest side effects, has the greatest anti- inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM composed of several plant extracts. This study was designed to investigate anti-inflammatory and immunomodulatory effects of BSASM. As a first step, $NF-{\kappa}B$ luciferase reporter assay was performed to know the involvement of BSASM in the production of proinflammatory cytokines because $NF-{\kappa}B$ element has been known to play a major role in expression of cytokine genes such as interleukin-8 (IL-8) or tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. LPS (lipolysaccharide)-induced $NF-{\kappa}B$ activation was inhibited by BSASM. In addition, we found the fact that BSASM inhibits LPS-induced produced production of IL-8 and $TNF-{\alpha}$ proinflammatory cytokines, indicating BSASM has anti-inflammatory effect. In interleukin-2 (IL-2) luciferase reporter assay in Jurkat T cells, BSASM reduced PHA (Phytohemagglutinin)-induced IL-2 luciferase activity, suggesting the possibility that BSASM might also have an immunomodulatory function in T cell-mediated immune response. Based on these results, we suggest the possibility that BSASM can be introduced to improve symptom of immune-related skin diseases, namely, atopic dermatitis.

• Clinical and Experimental Reproductive Medicine
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• 제44권3호
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• pp.146-151
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• 2017

Objective: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Methods: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. Results: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. $PPAR-{\gamma}$ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p= 0.034 and p= 0.018, respectively), but the expression of IL-6 and $TNF-{\alpha}$ mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the $PPAR-{\gamma}$, COX-2, IL-6, and $TNF-{\alpha}$ mRNA levels. Conclusion: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of $PPAR-{\gamma}$ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.

• Archives of Pharmacal Research
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• 제29권4호
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• pp.302-309
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• 2006

Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-${\alpha}$, IL-6, IL-10 and IFN-${\gamma}$, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 hand 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-${\gamma}$ and bronchoalveolar lavage (BAL) IL-6 and IFN-${\gamma}$ were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-${\alpha}$ were not. And levels of BAL TNF-${\alpha}$, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-${\alpha}$, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-${\alpha}$, IL-6, and IL-10 in lupuslike chronic inflammation syndrome compared with normal condition.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.217-225
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• 2021

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

• 대한본초학회지
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• 제32권3호
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• pp.1-7
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• 2017

Objective : The purpose of this study was to investigate the effects of Scrophulariae Radix Water Extract (SR) on the production of inflammatory mediators in RAW 264.7 mouse macrophages cells induced by lipopolysaccharide (LPS). Method : We examined effect of Scrophulariae Radix Extract on the cell viability of mouse macrophages cells. Futhermore, After 24 hours treatment we investigated anti-inflammatory effect of Scrophulariae Radix Extract by the production of Bio-Plex cytokine assay, concentrations of various cytokines such NO, $interleukin(IL)-1{\alpha}$, IL-3 and interferon inducible protein-10(IP-10). Result : No significant changes have been found in the mouse macrophge cell viability by the Scrophulariae Radix Extract at the concentration of 25, 50, 100 and $200{\mu}g/m{\ell}$. The water extract of Scrophulariae Radix significantly inhibited the production of NO in the LPS-induced macrophage at the concentration of 25, 50, 100 and $200{\mu}g/m{\ell}$. The water extract of Scrophulariae Radix significantly inhibited the production of $IL-1{\alpha}$, IL-3 and IP-10 in the LPS-induced macrophage at the concentration of 50, 100 and $200{\mu}g/m{\ell}$. Conclusion : The water extract of Scrophulariae Radix significantly inhibited the production of NO, $IL-1{\alpha}$, IL-3 and IP-10 at the concentration of $50{\mu}g/m{\ell}$ or higher in the LPS-induced macrophages with no changes in the cell viability of them. These results suggest that water extract of Scrophulariae Radix has anti-inflammatory effect related with its inhibition of proinflammatory cytokines such as $IL-1{\alpha}$, IL-3 and IP-10 in the LPS-induced macrophages.

• 대한본초학회지
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• 제24권2호
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• pp.49-56
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• 2009

Objectives : Inflammation is important event in the development of vascular diseases including hypertension, atherosclerosis, and restenosis. Bodusan (BDS) was a traditional Korean herbal medicine and widely used in treatment of gastrointestinal complaint and stomach ulcer. The aim of this study was to determine whether BDS and its components inhibit production of nitrite, PGE2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Methods : Cytotoxic activity of BDS and its components on RAW 264.7 cells was using 5-(3caroboxymcrophages. eth-oxyphenyj)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : Our results indicated that BDS and its components significantly inhibited the LPS-induced NO and PGE2 production. Moreover. BDS and its components inhibited iNOS and COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-11${\beta}$, IL-6 and MCP-1 formation in macrophages. Conclusions: These results indicate that BDS and its components have potential as an anti-inflammatory agent.

• 한국축산식품학회지
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• 제44권1호
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• pp.132-145
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• 2024

Sarcopenia, the age-related muscle atrophy, is a serious concern as it is associated with frailty, reduced physical functions, and increased mortality risk. Protein supplementation is essential for preserving muscle mass, and horse meat can be an excellent source of proteins. Since sarcopenia occurs under conditions of oxidative stress, this study aimed to investigate the potential anti-muscle atrophy effect of horse meat hydrolysate using C2C12 cells. A horse meat hydrolysate less than 3 kDa (A4<3kDa) significantly increased the viability of C2C12 myoblasts against H₂O₂-induced cytotoxicity. Exposure of C2C12 myoblasts to lipopolysaccharide led to an elevation of cellular reactive oxygen species levels and mRNA expression of proinflammatory cytokines, including tumor necrosis factor-α and interleukin 6, and these effects were attenuated by A4<3kDa treatment. Additionally, A4<3kDa activated protein synthesis-related proteins through the protein kinase B/mechanistic target of rapamycin pathway, while decreasing the expression of activity and degradation-related proteins, such as Forkhead box O3, muscle RING finger protein-1, and Atrogin-1 in dexamethasone-treated C2C12 myotubes. Therefore, the natural material A4<3kDa has the potential of protecting against muscle atrophy, while further in vivo study is needed.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.180-188
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• 2015

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-${\kappa}B$ and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권5호
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• pp.370-378
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• 2005

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-${\alpha}$, IL-1${\beta}$ and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines' level and frequencies of detection were compared. The level of IL-1${\beta}$was not significant different in all groups. but the level of TNF-${\alpha}$, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p<0.01) and the level of TNF-a(p<0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p<0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson's correlation coefficient (r=0.833)(p<0.001). The results indicated that the TNF-${\alpha}$, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-${\alpha}$, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders.

• Journal of Nutrition and Health
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• 제39권4호
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• pp.372-380
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• 2006

The purpose of this study was to investigate the association between inflammatory cytokines and chronic disease status in Korean elderly. The subjects were 248 elderly people aged over 65 years recruited from Health Center in Seoul. The subjects were classified into 3 groups based on their disease (diabetes, hypertension, and hyperlipidemia) status: subjects with one diagnosed disease of diabetes, hypertension, and hyperlipidemia fall into singular group (n=89), subjects with more than 2 disease into multiple group (n=39), and those with free of the diseases into normal (n=122). Anthropometric and biochemical characteristics, and dietary intakes were assessed. Dietary intakes were surveyed by 24-recall method. The means of IL-2, IL-6, MCP-1 and C3 were not differ among 3 groups. However, when subjects classified into tertiles of IL-6, MCP-1, TNF-$\alpha$ and C3 and frequencies of each fertile were compared, the multiple group showed significantly lower frequencies in lowest fertile than normal group (p<0.05), suggesting higher tendency of inflammatory responses. For hematological values, blood pressure, triglycerides, fasting blood glucose levels were highest in multiple group (p<0.05) compared to other 2 groups. BMI, body fat(kg), and triceps skinfold thickness were also significantly higher in multiple group than in 2 other groups(p<0.05). Moreover, the concentrations of IL-2, IL-6 and C3 were significantly correlated with hematologic values of fasting blood glucose, total cholesterol, LDL-cholesterol, and triglycerides or obesity factors such as triceps skinfold thickness, BMI, and body fat(%). Among singular and multiple group, the subjects with higher intakes for vitamins A, C, and E showed the higher level of IL-2 and the lower level of MCP-1, and C3. In conclusion, blood concentrations of triglycerides and proinflammatory cytokines, blood pressure, obesity parameters (BMI, body fat, triceps skinfold thickness) were higher in multiple group than in normal, but this result strongly suggest that the increasement of the vitamin A, C, and E intakes would modify the cytokine levels to reduce the inflammatory response in the elderly people with chronic diseases.