• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.79-85
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• 2009

Polyphenolic compounds are reported to have various pharmacological activities such as anti-oxidative, anti-cancerous, anti-inflammatory and anti-aging effects. Although numerous papers explore their functional roles in many different cellular actions, not many studies handle their structural features in anti-inflammatory responses. In this study, therefore, we examined structural role of substituted transstilbenes in their NO inhibitory and NF-${\kappa}B$ suppressive activities. Of 10 compounds tested, 4 compounds (cinnamic acid, resveratrol, piceatannol and curcumin) displayed NO inhibitory activities in a dose-dependent manner. Similarly, these compounds blocked LPS-induced cytotoxicity of RAW264.7 cells. All NO inhibitory compounds also inhibited $I{\kappa}B{\alpha}$ phosphorylation, a hallmark for NF-${\kappa}B$ activation. However, these inhibitory compounds exhibited distinct suppressive pattern in tumor necrosis factor (TNF)-${\alpha}$- or phorbol-12-myristate-13-acetate (PMA)-induced NF-${\kappa}B$ and AP-1 activation. According to structure-activity relationship study, polarity and size of ring B seem to be important for diminishing NO production. Therefore, our data suggest that substituted trans-stilbenes can be developed as novel anti-inflammatory drug or further developed as lead compounds for another improvement.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.262-266
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• 1995

Bacterial lipopolysaccharide (LPS) is one of the most potent inducers of various cytokines nad other proinflammatory mediators in macrophages. Although pathophysiological consequences of LPS-induced responses are well established, the mechanisms through which LPS-generated singals are transduced remain unclear. In the present study, we attempted to determine early intracellular events after LPS binding which transduced the signal for the induction of arachidonic acid metabolism in rat alveolar macrophages. While H-7, a protein kinase C(PKC) inhibitor, did not affect LPS-stimulated prostaglandin synthesis, staurosporine enhanced archidonic acid etabolism in macropahages treated with LPS. Phorbol-12-myristate-13 acetate snesitive to LPS compare with control group. PMA and H-7 did not alter the effect of flucose. Pertussis toxin did not show nay effect, thus pertussis toxin snesitive G-protein pathway appears not to play a role in this experimental system. Genistein and tyrphostin 25, protein tyrosine kinase 9PTK) inhibitors, markedly inhibited prostaglandin synthesis in macrophages nal transduction events leading to icnreased macrophage arachidonic acid metabolism.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.573-581
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• 2005

Flavonoids, a group of low molecular weight phenylbenzopyrones, have various pharmacological properties including antioxidant activity, anticancer, and immunomodulatory effects. In the present study, lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate/phytohemagglutinin (PMA/PHA) were used as stimulants for RAW 264.7 macrophages and human peripheral blood mononuclear cell (hPBMC), and tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-2 productions were measured. In addition, flavonoids were examined for their effects on LPS-induced NO production in RAW 264.7 macrophages. The results showed that all compounds were not strongly cytotoxic at the tested concentrations on hPBMC and RAW 264.7 macrophages. On immunomodulatory properties, catechin, epigallocatechin (EGC), naringenin, and fisetin repressed NO production and TNF-${\alpha}$ secretion. Furthermore, catechin, epigallocatechin gallate (EGCG), epicatechin (EC), luteolin, chrysin, quercetin, and galangin increased IL-2 secretion while EGC, apigenin, and fisetin inhibited the secretion. These results indicated that flavonoids have the capacity to modulate the immune response and have a potential anti-inflammatory activity. There was no obvious structure-activity relationship regard to the chemical composition of the flavonoids and their cell biological effects.

• Bulletin of the Korean Chemical Society
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• v.30 no.8
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• pp.1811-1816
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• 2009

An extensive phytochemical investigation of the polar fractions of a methanolic extract of Egyptian medicinal food, black cumin (seeds of Nigella sativa L.) led to the isolation of two new triterpene saponins, named sativosides A and B (1-2), along with four known saponins (3-6). Sativoside A (1) is the first example of saponins containing 18-ene triterpene aglycon not only in this Nigella genus but also in the family Ranunculaceae. The structure of the new saponins was elucidated mainly by a combination of 1D and 2D NMR data, together with HRFABMS and acid hydrolysis. Three compounds (1-3) showed the significant inhibition effect of phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced production of IL-6 in a human mast cell (HMC-1) line.

• BMB Reports
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• v.55 no.3
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• pp.136-141
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• 2022

Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.

• Reproductive and Developmental Biology
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• v.28 no.3
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• pp.187-190
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• 2004

Protein kinase C exists as a family of serine/threonine kinases which are broadly classified into three groups as cPKC nPKC and aPKC depending on their cofactor requirements. Previous studies have shown that the role of PKC in the process of mouse oocyte maturation. For example, phorbol 12-myristate 13-acetate which is known as an activator of cPKC and nPKC inhibits germinal vesicle break down and 1st polar body extrusion in maturing oocytes. In this study, the effect of thymeleatoxin, a specific activator of cPKC not nPKC, was tested comparing with PMA to address the roles of cPKC and nPKC during mouse oocyte maturation. Cumulus-oocyte complex were cultured in M16 medium for 6 or 12 hr with each of these PKC activators to investigate the effect of germinal vesicle breakdown (GVBD) or the extrusion of 1st polar body. IC/sup 50/ of GVBD were at concentrations of 50nM in PMA and 400nM in thymeleatoxin and of 1st polar body extrusion were 20nM in PMA and 200nM in thy- meleatoxin. The results suggest that activation of nPKC is more closely related to the inhibition of GVBD and 1st polar body extrusion than activation of cPKC. Additionally, we found that the oocytes inhibited 1st polar body extrusion with PMA or thymeleatoxin were arrested in metaphase I of first meiosis.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.2
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• pp.31-48
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• 2004

Objective : KagamJwagwiEum(KJE) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of KJE, the author examined cytotoxicity and inflammatory cytokines secretion with human leukemic mast cell line, HMC-1. Methods: HMC-1 was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. KJE by itself had no effect on viability of HMC-l. The effects of KJE on the secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$, interleukin(IL)-6 and IL-8 from HMC-1 were evaluated with enzyme-linked immunosorbent assay. Results : KJE inhibited PMA plus A23187-induced $TNF-{\alpha}$ and IL-6 secretion. But KJE had no effect IL-8 secretion: KJE had immunoregulatory effects on cytokines, increased secretion of NO and $TNF-{\alpha}$ but did not effect IL-12 secretion when the cells were primed and trigged with $IFN-{\gamma}$ in the peritoneal macrophages of C57BL/6 mice. Conclusions : Taken together, these results suggest that KJE inhibit the production of inflammatory cytokines in HMC-1 cells and activate macrophages.

• The Korean Journal of Zoology
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• v.39 no.1
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• pp.12-20
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• 1996

A multipotential hematopojetic cell line, 1(562 cell, was differentiated into megakaryocyte by a chemical inducer, PMA, with an enhanced expression of gpIlla accompaning with a distinct morphological change. On the other hand, 1(562 cells were differentiated into erythrocytes by other chemical inducers, DMSO or butyrate, with a concomitant increase in hemoglobin accumulation. An antigen of apparent molecular weight of 61 kDa was identified on the surface of 1(562 cells by using monoclonal antibody raised against 1(562 cells. The antigen was considered to be a glycoprotein molecule rich in sialic acids and the epitope of antigen was sensitive to neuraminidase digestion or peroxidase oxidation, but resistant to heat treatment. The 61 kDa surface antigen was increased or decreased in its expression along differentiation of 1(562 cells into megakaryocytes or erythrocytes, respedively.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.496-504
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• 2022

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

• Biomedical Science Letters
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• v.18 no.2
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• pp.104-111
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• 2012

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.