• Molecules and Cells
• /
• 제41권3호
• /
• pp.244-255
• /
• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• 대한임상검사과학회지
• /
• 제48권3호
• /
• pp.176-182
• /
• 2016

대식세포에서 염증반응이 진행되면, interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) 등의 cytokine들이 발현되어 inducible nitric oxide synthase (iNOS), prostaglandin E2(PGE2) 등의 염증유발인자가 생성된다. 오가피, 우슬, 두충 각각의 추출물이 어느 정도의 항 염증 효능을 보이며 어떤 pro-inflammatory cytokine의 발현을 억제하는지에 대한 연구를 진행하였다. 오가피, 우슬, 두충은 물 추출하고 동결 건조시켰다. 각각의 추출물의 구성 성분들이 잘 추출되었는지 확인하기 위하여 지표물질인 acanthoside D, 20-hydroxyecdysone, pinoresinol diglucoside를 HPLC로 분석하였다. 항 염증 효능을 확인하기 위하여 lipopolysaccharide (LPS)로 RAW 264.7 세포주를 자극하여 염증 반응을 일으킨 상태에서 각각의 추출물을 농도 별로 처리하고 NO assay를 통해 항 염증 효능을 확인하였으며 real time PCR로 pro-inflammatory cytokine들의 발현량을 측정하였다. 결과적으로 각각의 추출물은 지표성분들이 검출되었으며 오가피와 우슬이 두충보다 NO assay에서 높은 활성을 보였다. Cytokine 발현량 측정에서는 오가피와 우슬은 iNOS와 IL-6의 발현을 억제하였고, 우슬은 TNF-${\alpha}$의 발현을 억제하였다. 우리나라는 전통적으로 약재를 조합하여 처방하여 왔다. 본 연구는 관절염에 전통적으로 사용해 오던 약재들이 어떤 기전에 의하여 항 염증 반응을 보이는지 확인하고 이들을 조합하여 사용하였을 때 어떤 근거에 의하여 시너지 효능을 보이는지 확인하였다.

• 대한한의학방제학회지
• /
• 제28권2호
• /
• pp.147-155
• /
• 2020

PURPOSE : Andrographis Herba is used as a traditional herbal medicine in the Asian countries for the treatment common cold, fever, diabetes, hypertension, hepatitis, skin infections, snake bite, and other diseases. In this study, we investigated the anti-inflammatory effect of MeOH extract of Andrographis Herba (AHME) on LPS-activated Raw 264.7 cells. METHODS : Cell viability was determined by MTT assay. Nitric oxide (NO) production was determined by Griess reagent. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Expression levels of pro-inflammatory proteins were determined by Western blot analysis. RESULTS : Production of NO in LPS activated Raw 264.7 cells, was significantly decreased by pre-treatment with 3-30 ㎍/mL of AHME. Production of pro-inflammatory mediators such as TNF-α and IL were significantly decreased by AHME 30 ㎍/mL pre-treatment. AHME significantly decreased p-IκB and NF-κB expression. CONCLUSION : The results of this study indicate that AHME could inhibit the acute inflammatory response, via modulation of NF-κB activation.

• Radiation Oncology Journal
• /
• 제32권3호
• /
• pp.103-115
• /
• 2014

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

• 한국식품저장유통학회지
• /
• 제30권1호
• /
• pp.65-77
• /
• 2023

In this study, we investigated the immunological properties of six strains of Acetobacter pasteurianus through nuclear factor-kappa B/activator protein-1 (NF-κB/AP-1) transcription factor activation and nitric oxide (NO) and cytokine production in macrophages. We found that the six A. pasteurianus strains had no significant inhibitory effect on the cell viability of RAW-Blue^TM cells at the concentration of (25, 50, 100 CFU/macrophage). The production of NO and cytokines (TNF-α, IL-1β, and IL-6) showed different abilities of immune activation for each strain, and it was 0.7 to 0.9 times higher than that of the LPS (100 ng/mL, v/v) positive control and 7 to 8 times superior to that of the negative control group. To explore the underlying mechanism, we evaluated the mRNA expression of pro-inflammatory genes. Consequently, we found that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression including genes expression of cytokines were elevated by the six A. pasteurianus treatment. These results suggested that the six strains of A. pasteurianus have an excellent industrial application value as a functional material for the purpose of enhancing immune function.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권5호
• /
• pp.413-420
• /
• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• 대한화학회지
• /
• 제65권5호
• /
• pp.327-332
• /
• 2021

Shiranuhi is a fruit of Citrus species widely cultivated in Jeju Island, Korea. From an extract of Shiranuhi tree branches were identified five polymethoxyflavones possessing anti-inflammatory effects; nobiletin (1), sinensetin (2), tetramethylscutellarein (3), 6-hydroxy-5,7,3',4'-tetramethoxyflavone (4) and 5-desmethylsinensetin (5). Evaluation of the activities was conducted by monitoring the production of nitric oxide (NO), prostaglandin E₂ and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as the levels of iNOS and COX-2 protein expression in LPS-induced RAW264.7 cells. Among the isolates, the compound 4 exhibited the most significant NO inhibition, and suppressed the levels of iNOS and related cytokines. Therefore, it was suggested that the extract and constituents from Shiranuhi tree branches could be useful as anti-inflammatory ingredient.

• 동의생리병리학회지
• /
• 제18권2호
• /
• pp.490-495
• /
• 2004

Brain cells produce cytokines and chemokines during the inflammatory process of many neuronal diseases both in animal models and in patients. Inflammatory cytokines are the main responsible for the onset of inflammatory cascade. During the past decade, a growing corpus of evidence has indicated an important role of these cytokines in the development of brain damage. ZhenganXifeng-tang (ZGXFT) is a Korean herbal prescription, which has been successfully applied for the treatment of various neuronal diseases. However, its effect in experimental models remains unknown. Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in inflammatory disease. An inflammatory response associated with β-amyloid (Aβ) and interleukin (IL)-1β is responsible for the pathology of inflammation disease. To investigate the biological effect of ZGXFT, the author examined cytotoxicity, effect of cytokines (IL-6 and IL-8) secretion and expression of cyclooxygenase-2 (COX-2) on human astrocytoma cell line U373MG stimulated with IL-1β plus M fragment 25-35 (Aβ [25-35]). ZGXFT by itself had no effect on cell viability on human astrocytoma cells. The secretion of IL-6 and IL-8 was inhibited by pre-treatment with ZGXFT in human astrocytoma cells. In addition, the expression of COX-2 was induced by IL-1β plus AB[25-35] and was partially inhibited by treatment with ZGXFT. The author demonstrates the regulatory effects of inflammatory reactions by ZGXFT in human astrocytes for the first time and suggest the anti-inflammatory effect of ZGXFT may reduce and delay pathologic events of inflammatory disease.

• Biomolecules & Therapeutics
• /
• 제18권2호
• /
• pp.135-144
• /
• 2010

The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the initiation and progression of atherosclerosis. In fact, inflammatory responses in vascular endothelium are primarily regulated through oxidative stress-mediated signaling pathways leading to overexpression of pro-inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion molecules in endothelial cells and their close interactions facilitate recruiting and adhering blood leukocytes to vessel wall, and subsequently stimulate transendothelial migration, which are thought to be critical early pathologic events in atherogenesis. Although interleukin-4 (IL-4) was traditionally considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies have provided robust evidence that IL-4 exerts pro-inflammatory effects on vascular endothelium and may play a critical role in the development of atherosclerosis. The cellular and molecular mechanisms responsible for IL-4-induced atherosclerosis, however, remain largely unknown. The present review focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS) generation as well as the pivotal role of ROS in IL-4-induced vascular inflammation. These studies will provide novel insights into a clear delineation of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation and subsequent development of atherosclerosis. It will also contribute to novel therapeutic approaches for atherosclerosis specifically targeted against pro-oxidative and pro-inflammatory pathways in vascular endothelium.

• 한국임상수의학회지
• /
• 제36권3호
• /
• pp.145-149
• /
• 2019

Previous report has suggested that the albumin levels were reduced in the peripheral blood mononuclear cells (PBMCs) and consequently oxidative stress was elevated in streptozotocin (STZ)-induced diabetic rats as albumin is the predominant antioxidant in plasma. In this study, we suggest that the levels of pro-inflammatory cytokine such as interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) were increased by approximately 3.4- and 2.9-fold, respectively, in the serum of STZ-diabetic rats, compared to those of normal rat. In addition to the cytokines, the levels of C-reactive protein (CRP) were also about 3.6-fold higher, indicating that STZ induced a pro-inflammatory response in rat blood. However, when purified rat albumin was externally co-administrated with STZ through the tail vein, the serum levels of IL-6, $TNF-{\alpha}$, and CRP were markedly reduced, although the values were still higher than those of normal (non-diabetic) rats. Albumin administration also decreased STZ-induced oxidative stress in serum and PBMCs. Moreover, the decrease in cytokine and CRP levels was dependent on the dose of injected albumin. These results suggest that STZ-induced pro-inflammation and oxidative stress in rat blood might be attenuated by treatment with exogenous albumin.