• Journal of Ginseng Research
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• v.36 no.2
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• pp.146-152
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• 2012

Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-${\kappa}B$transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-${\alpha}$-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-${\alpha}$-induced NF-${\kappa}B$transcription activity and NF-${\kappa}B$-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with $IC_{50}$ values of $12.05{\pm}0.82$ and $8.84{\pm}0.99\;{\mu}M$, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-${\alpha}$-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-${\alpha}$-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.200-208
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• 2011

Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

• Journal of Applied Biological Chemistry
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• v.53 no.3
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• pp.147-153
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• 2010

$\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.436-446
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• 2018

Background: The potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated. Methods: We used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination. Results: Pretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein $(MBP)_{68-82}$ peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-${\gamma}$, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor ${\beta}1$, transforming growth factor ${\beta}$, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-${\kappa}B$ signaling pathways in microglia/macrophages, T cells, and astrocytes. Conclusion: Our findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-${\kappa}B$ signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.

• Archives of Pharmacal Research
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• v.29 no.7
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• pp.591-597
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• 2006

Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor $(NF)-{\kappa}B$ inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited $NF-{\kappa}B$ transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $5.8\;{\mu}M$. The compound was also effective in blocking $NF-{\kappa}B$ transcriptional activities elicited by the expression vector encoding the $NF-{\kappa}B$ p65 or p50 subunits bypassing the inhibitory kB degradation signaling $NF-{\kappa}B$ activation. The macrophages markedly increased their $PGE_2$ and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced $PGE_2$ and NO production with $IC_{50}$ values of $8.7\;{\mu}M$ and $6.4\;{\mu}M$, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a $NF-{\kappa}B$ inhibitor that attenuates LPS-induced production of $PGE_2$ or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica.

• Journal of Sasang Constitutional Medicine
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• v.21 no.1
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• pp.139-149
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• 2009

1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.11
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• pp.1776-1788
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• 2019

Objective: The demands for measures to improve disease resistance and productivity of livestock are increasing, as most countries prohibit the addition of antibiotics to feed. This study therefore aimed to uncover functional feed additives to help enhance livestock immunity and disease resistance, using Acanthopanax sessiliflorus fruit extract (ASF). Methods: ASF was extracted with 70% EtOH, and total polyphenolic and catechin contents were measured by the Folin-Ciocalteu and vanillin assay, respectively. The 3D4/31 porcine macrophage cells ($M{\Phi}$) were activated by phorbol 12-myristate 13-acetate (PMA), and cell survival and growth rate were measured with or without ASF treatment. Flow-cytometric analysis determined the lysosomal activity, reactive oxygen species levels (ROS), and cell cycle distribution. Nuclear factor kappa B ($NF-{\kappa}B$) and superoxide dismutase (SOD) protein expression levels were quantified by western blotting and densitometry analysis. Quantitative polymerase chain reaction was applied to measure the lipid metabolism-related genes expression level. Lastly, the antibacterial activity of 3D4/31 $M{\Phi}$ cells was evaluated by the colony forming unit assay. Results: ASF upregulated the cell viability and growth rate of 3D4/31 $M{\Phi}$, with or without PMA activation. Moreover, lysosomal activity and intracellular ROS levels were increased after ASF exposure. In addition, the antioxidant enzyme SOD2 expression levels were proportionately increased with ROS levels. Both ASF and PMA treatment resulted in upregulation of $NF-{\kappa}B$ protein, tumor necrosis factor $(TNF){\alpha}$ mRNA expression levels, lipid synthesis, and fatty acid oxidation metabolism. Interestingly, co-treatment of ASF with PMA resulted in recovery of $NF-{\kappa}B$, $TNF{\alpha}$, and lipid metabolism levels. Finally, ASF pretreatment enhanced the in vitro bactericidal activity of 3D4/31 $M{\Phi}$ against Escherichia coli. Conclusion: This study provides a novel insight into the regulation of $NF-{\kappa}B$ activity and lipid metabolism in $M{\Phi}$, and we anticipate that ASF has the potential to be effective as a feed additive to enhance livestock immunity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.320.3-321
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• 2002

Nuclear factor ${\kappa}$B (NF-${\kappa}$B) represents a family of eukaryotic transcription factors participating in the regulation of various cellular genes. Since aberrant regulation of NF-${\kappa}$B has been implicated in the pathogenesis of various diseases including inflammation. asthma. atherosclerosis. AIDS. septic shock. arthritis, and cancer. this transcription factor has been shown to be an interesting target of new drug discovery. (omitted)

• Advances in Traditional Medicine
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• v.10 no.3
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• pp.155-164
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• 2010

Lycii fructus is the fruit of Lycium chinense Miller and is part of the Solanaceae family. Lycii fructus produces various effects such as hypotensive, hypoglycemic, anti-pyretic, and anti-stress activities. Lycii fructus is known to contain betaine, carotene, nicotinic acid, zeaxanthin, and cerebroside. In the present study, the effects of Lycii fructus aqueous extract on lipopolysaccharide (LPS)-induced inflammation in murine raw 264.7 macrophage cells were investigated. In this study we utilized the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), Western blotting, and nitric oxide (NO) detection. Lycii fructus aqueous extract suppressed NO production by inhibiting the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-$\alpha$) mRNA and iNOS protein in murine raw 264.7 macrophage cells. Also, Lycii fructus aqueous extract suppressed the activation of nuclear factor-kappa B (NF-${\kappa}B$) in the nucleus. These results demonstrated that Lycii fructus aqueous extract causes an anti-inflammatory effect that was likely produced by the suppression of iNOS expression through the down-regulation of NF-$\hat{e}B$ binding activity.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.261-268
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• 2013

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.