• BMB Reports
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• 제48권10호
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• pp.549-558
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• 2015

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• IMMUNE NETWORK
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• 제19권1호
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• pp.3.1-3.17
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• 2019

Aging is a complex process associated with dysregulation of the immune system and low levels of inflammation, often associated with the onset of many pathologies. The lacrimal gland (LG) plays a vital role in the maintenance of ocular physiology and changes related to aging directly affect eye diseases. The dysregulation of the immune system in aging leads to quantitative and qualitative changes in antibodies and cytokines. While there is a gradual decline of the immune system, there is an increase in autoimmunity, with a reciprocal pathway between low levels of inflammation and aging mechanisms. Elderly C57BL/6J mice spontaneously show LGs infiltration that is characterized by Th1 but not Th17 cells. The aging of the LG is related to functional alterations, reduced innervation and decreased secretory activities. Lymphocytic infiltration, destruction, and atrophy of glandular parenchyma, ductal dilatation, and secretion of inflammatory mediators modify the volume and composition of tears. Oxidative stress, the capacity to metabolize and eliminate toxic substances decreased in aging, is also associated with the reduction of LG functionality and the pathogenesis of autoimmune diseases. Although further studies are required for a better understanding of autoimmunity and aging of the LG, we described anatomic and immunology aspects that have been described so far.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.186-196
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• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1612-1620
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• 2015

양파 껍질 에탄올 추출물(OPEE)의 in vitro 및 in vivo에서 항염증 효과를 알아보기 위해 lipopolysaccharide(LPS)로 활성화된 RAW 264.7 세포로부터 분비되는 염증 관련 매개인자들의 발현량과 ICR 마우스모델을 이용한 귀 부종 및 조직 분석을 진행하였다. NO 및 염증성 cytokine(IL-6, $IL-1{\beta}$ 및 $TNF-{\alpha}$)의 분비량이 OPEE에 의해 농도 의존적으로 감소함을 확인하였다. iNOS 및 COX-2의 발현량은 LPS에 의해 증가하였으나, OPEE 처리에 의해 농도 의존적으로 발현량이 감소하였다. 전사인자인 $NF-{\kappa}B$의 활성과 인산화효소인 MAPKs(p-38, JNK 및 ERK)에서도 LPS에 의해 증가된 발현량이 OPEE에 의해 억제됨을 확인하였다. 따라서 NO 및 염증성 cytokine의 분비량 감소는 $NF-{\kappa}B$와 MAPKs의 활성 저해에 의한 것임을 확인하였다. In vivo 실험에서는 croton oil로 귀 부종을 유발한 마우스에 OPEE를 처리하였을 때 prednisolone 처리구와 유사한 수준으로 귀 부종이 억제되었으며, 귀 조직 관찰에서도 경피 및 진피의 두께와 진피로 침윤된 mast cell의 수도 억제됨을 확인하였다. 이상의 결과 OPEE는 항염증 소재로서 염증을 예방하거나 치료하는 데 이용 가능성이 높음을 제시한다.

• 대한본초학회지
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• 제28권4호
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• pp.83-92
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• 2013

Objectives : Lespedeza Cuneata has been used to treat leukorrhea, asthma, stomach pain, diarrhea, acute mastitis, in Korean traditional medicine. According to recent studies, Lespedeza Cuneata has antioxidation, hypoglycemia, cell protective, insulin secretion, whitening, corpora cavernosa smooth muscle relaxation and antimicrobial activities, but it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Lespedeza Cuneata MeOH extract (LCE) in vivo and in vitro. Methods : In vitro, inflammatory mediators, such as cytokines, nitric oxide and prostaglandin $E_2$ were detected after the addition of LPS with or without LCE in Raw 264.7 macrophage cell line. In vivo, anti-edema effect of LCE was determined in the carrageenan-induced paw edema model in rats. Results : In vitro assay, LCE decreased release of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) via suppression of iNOS and COX-2 expression. LCE inhibited the phosphorylation of $I{\kappa}B$ indicating the suppression of NF-${\kappa}B$ pathway. In vivo assay, LCE significantly inhibited the formation of paw edema induced by carrageenan injection in rats. LCE effectively inhibited increases of hind paw skin thickness and inflammatory cell infilterations. Conclusion : These findings demonstrate that LCE has inhibitory effect on inflammatory mediators in LPS-activated Raw 264.7 cells and on paw edema in carrageenan-stimulated rats, showing the possibility of anti-inflammatory use of Lespedeza Cuneata.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.283-290
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• 2016

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.463-468
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• 2010

T-cell activation depends on signals received by the T-cell receptor and CD28 co-stimulatory receptor. Since B7.1 and B7.2 molecules expressed on the surface of antigen presenting cells provide co-stimulatory signals through CD28 to T-cells, an inhibitor of CD28-B7.1/B7.2 binding has been proposed as a therapeutic agent for suppression of excessive T-cell activity. Although anti-B7.1/B7.2 antibodies are known to block B7.1 and B7.2 molecules, their effects on intracellular events in antigen presenting cells remain unclear. In this study, anti-B7.1/B7.2 antibodies decreased secretion of nitric oxide and pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited $I{\kappa}B{\alpha}$ phosphorylation and down-regulated expression of co-stimulatory molecules including B7.1, B7.2, and PD-L1 in LPS-stimulated peritoneal macrophages. These findings suggest that CTLA4-Ig and anti-B7.1/B7.2 antibodies may be candidates to treat chronic inflammatory diseases and autoimmune responses caused by excessive activation of both T-cells and macrophages.

• 대한한의학방제학회지
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• 제25권4호
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• pp.537-551
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• 2017

Objectives : Jinnoe-san (JNS) is a novel herbal formula consisting of five oriental medicinal herbs including Polygalae Radix, Prunellae Spica, Perillae Herba, Betulae Cortex, and Lonicerae Flos. In this study, we investigated the effects and molecular mechanism of JNS on Parkinson's disease in vitro model. Methods : The effects of JNS on 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in SH-SY5Y cells were evaluated with a cell viability assay, flow cytometry, and western blots analysis. The effects of JNS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay, enzyme linked immunosorbent assays, and western blots analysis. Result : $MPP^+$-induced cell death in SH-SY5Y cells was significantly reduced by JNS pre-treatment in a dose-dependent manner. JNS inhibited the production of reactive oxygen species, mitochondria dysfunction, and apoptosis induced by $MPP^+$ in SH-SY5Y cells. Furthermore, JNS significantly activated Akt and ERK in SH-SY5Y cells and the ability of JNS to prevent mitochondria dysfunction by $MPP^+$ was antagonized by pre-treatment of LY294002 and PD98059, an Akt and ERK inhibitor, respectively. In addition, JNS inhibited LPS-induced NO and $PGE_2$ production as well as iNOS expression and secretion of TNF-${\alpha}$, pro-inflammatory cytokines without affecting the cell viability. JNS also suppressed LPS-induced ERK activation. Conclusions : These results demonstrate that JNS has a protective effect on the dopaminergic neurons against $MPP^+$-induced neurotoxicity and anti-inflammatory effect on the LPS-stimulated microglia. These findings provide evidences for JNS to be considered as a new prescription for treating Parkinson's disease.