Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase

Kim, Young‐Ho; Lee, SangHan; Lee, Jai-Youl; Choi, Sang-Won; Park, Jong‐Wook; Kwon, Taeg Kyu

doi:10.1016/j.ejphar.2004.04.040

Cited by 95 publications

(58 citation statements)

References 28 publications

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“…Phosphorylation of IκB-α results in its proteolytic degradation by ubiquitination [15], thus liberating the NF-κB complex and enabling translocation to the nucleus with subsequent activation of pro-inflammatory genes such as iNOS [15]. In addition, mitogen-activated protein kinase (MAPK) signaling is considered to play important roles in cell-cell adhesion [31,33] and has been implicated in the regulation of iNOS expression [4,5,20]. In this study, the underlying mechanisms by which Maesil extract dampens the inflammatory response were investigated.…”

Section: Introductionmentioning

confidence: 99%

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Lee¹,

Park²,

Lee³

et al. 2015

Journal of Life Science

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Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Lee¹,

Park²,

Lee³

et al. 2015

Journal of Life Science

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“…Although to the author's knowledge only few studies exist to date that investigated the anti-inflammatory in vitro effect of TPL in chondrocytes [24], its effects were tested in a collagen-induced arthritis mouse model in vivo. Results indicate that TPL can reduce inflammatory responses and cartilage damage in the joint tissues by inhibiting expression of MMP3, MMP13, PGE2, COX-2, IL-1b, IL-6, TNF-a [16][17][18]. While we can confirm the inhibition of MMP3, MMP13 and IL-6 in human IVD cells in vitro, expression of TNF-a was induced in our system and will thus be subject to further scrutiny in next experiments.…”

Section: Discussionmentioning

confidence: 64%

“…Based on the promising gene expression results, we further sought to investigate the underlying molecular mechanism. Findings in the literature indicate that the NFjB pathway is one of the molecular mechanisms underlying the cellular responses observed after TPL treatment [16][17][18][19][20]. However, the effects of TPL seem to be mediated by a complex interplay of various signaling mechanisms, including the MAP kinases p38 [17], ERK [21] or JNK [17,18] as well as the transcription factor AP-1 [19].…”

Section: Discussionmentioning

confidence: 99%

“…However, molecular biological research of the past decades indicates that the MAP kinase pathways as well as the transcription factor nuclear factor-jB (NF-jB) are the major mechanisms regulating inflammatory responses in vivo and in vitro. Additionally, TPL has been described to not only influence NF-jB [16][17][18][19][20] and MAP kinases [17,18,21], but also to reduce levels of RNA polymerase II (=enzyme that is essential in the process of transcription) in cancer cells [5], thus possibly explaining the broad spectrum of genes whose expression is influenced upon TPL treatment.…”

Section: Introductionmentioning

confidence: 99%

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Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells

et al. 2011

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Introduction Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. Materials and methods In order to investigate the antiinflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1b prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-a, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-jB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). Results Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-a at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-jB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. Conclusions In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

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“…The following three well-defined mitogen-activated protein kinases (MAPKs)-extracellular signal-regulated kinase (ERK), p38, and c-Jun NH 2 -terminal kinase (JNK)-have been implicated in the transcriptional regulation of the iNOS gene. Also, specific MAPK inhibitors suppress the expression of the iNOS gene (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Codium fragile Ethanol Extraction Inhibited Inflammatory Response through the Inhibition of JNK Phosphorylation

Han

Kim²,

Lee³

et al. 2010

JFN

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Codium fragile (CF) is an edible green alga consumed as a traditional food source in Korea. In this study, the ethanol extract of CF was evaluated to determine if it has anti-inflammatory activity. Lipopolysaccharide (LPS), a toxin from bacteria, is a potent inducer of inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. Therefore, we studied whether CF extracts have an anti-inflammatory effect in LPS-induced murine macrophage cell lines (RAW 264.7). In the present study, IL-6 production was measured using an enzymelinked immunosorbent assay (ELISA), prostaglandin E 2 (PGE 2 ) production was measured using the EIA kit, and cyclooxygenase (COX)-2 and mitogen-activated protein kinase (MAPK) activation were determined by Western blot analysis. IL-6 mRNA, COX-2 mRNA and iNOS mRNA expression were measured using reverse transcriptionpolymerase chain reaction (RT-PCR). The results indicated that CF extracts inhibit LPS-induced IL-6, NO and PGE 2 production in a dose-dependent manner, as well as expression of iNOS and COX-2. CF extracts significantly inhibited LPS-induced c-Jun N-terminal kinase (JNK) 1/2 phosphorylation. Taken together, these findings may help elucidate the mechanism by which CF modulates RAW 264.7 cell activation under inflammatory conditions.

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Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase

Cited by 95 publications

References 28 publications

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells

Codium fragile Ethanol Extraction Inhibited Inflammatory Response through the Inhibition of JNK Phosphorylation

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