Differential anti-inflammatory pathway by xanthohumol in IFN-γ and LPS-activated macrophages

Cho, Young-Chang; Kim, Hyun Jung; Kim, Young‐Jun; Lee, Kwang Youl; Choi, Hyun Jin; Lee, Ik‐Soo; Kang, Bok Yun

doi:10.1016/j.intimp.2007.12.017

Cited by 87 publications

(79 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,[21][22][23][24] We demonstrated here that C4 and C10 potently suppressed iNOS induction and NO production caused by LPS, but did not affect NF-κB, JNK, and p38 pathways. Interestingly, C10, but not C4, potently inhibited the MEK/ERK pathway.…”

Section: Discussionmentioning

confidence: 65%

Newly Synthesized ‘Hidabeni’ Chalcone Derivatives Potently Suppress LPS-Induced NO Production <i>via</i> Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

Hara

Ikeda

Ninomiya

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Chalcones are open-chain flavonoids that are biosynthesized in various plants. Some of them possess anti-inflammatory activity. We previously found that chalcone glycosides from Brassica rapa L. 'hidabeni' suppress lipopolysaccharide (LPS)-induced nitric oxide (NO) production in rat microglia highly aggressively proliferating immortalized (HAPI) cells. In this study, to explore chalcone derivatives with potent NO inhibitory activity, we synthesized ten compounds based on 'hidabeni' chalcone and examined their effects on LPS-triggered inducible NO synthase (iNOS) expression and NO production. Compounds C4 and C10 potently inhibited NO production (IC 50 : 4.19, 2.88 µM, respectively). C4 and C10 suppressed LPS-induced iNOS expression via the inhibition of the signal transduction and activator of transcription 1 (STAT1), but not nuclear factor-kappa B (NF-κB), c-Jun N terminal kinase (JNK), and p38, pathways. C10, but not C4, inhibited activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. C4 and C10 also suppressed LPS-induced expression of interferon regulatory factor 1 (IRF-1), which is an important transcription factor involved in iNOS expression. Our findings indicate that these chalcone derivatives are candidate compounds for preventing microglia-mediated neuroinflammation. Key words microglia; nitric oxide (NO); inducible NO synthase; lipopolysaccharide; interferon β; signal transduction and activator of transcription 1 (STAT1)There is growing evidence that inflammation is involved in the pathogenesis of neurodegeneration in many central nervous system (CNS) disorders, such as cerebral ischemia and Alzheimer's disease.1-3) Microglia, resident immune cells in the CNS, are activated in response to neuronal injury. Activated microglia produce inflammatory mediators including nitric oxide (NO), superoxide, and proinflammatory cytokines, leading to a robust neuroinflammatory response.4,5) NO produced by inducible NO synthase (iNOS) rapidly reacts with superoxide to form a highly toxic product, peroxynitrite. This product has been shown to exaggerate neuropathological injury.6) Therefore, suppression of iNOS expression is thought to ameliorate microglia-mediated neurodegeneration.The induction of iNOS has been reported to be mediated via activation of toll-like receptor 4 (TLR4) in microglia/macrophages.7) Lipopolysaccharide (LPS), an exogenous TLR4 ligand, stimulates TLR4 and provokes several signaling pathways including nuclear factor-κB (NF-κB) and the mitogenactivated protein kinase (MAPK) family (c-Jun N terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK)). 8,9) In addition, activation of the interferon-β (IFN-β) autocrine loop caused by LPS also plays a key role in LPSinduced iNOS expression.10) Previous reports have demonstrated that TLR4 participates in the exacerbation of ischemic brain injury. 7,11) It has been demonstrated that damaged or dying cells after cerebral ischemia release damage-associated molecular pattern molecules such as high mobility group box 1...

show abstract

Section: Discussionmentioning

confidence: 65%

Newly Synthesized ‘Hidabeni’ Chalcone Derivatives Potently Suppress LPS-Induced NO Production <i>via</i> Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

Hara

Ikeda

Ninomiya

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Its inhibited mechanism occurs through induction of the detoxification enzyme NAD (P) H: quinone oxidoreductase-1 (NQO1) [10]. XN also shows immunomodulatory activity in macrophage cell lines [11,12], but the efficient delivery system of XN remains to be searched.…”

Section: Introductionmentioning

confidence: 99%

Effect of blending HA-g-PLLA on xanthohumol-loaded PLGA fiber membrane

Qiao

Jiang

Song

et al. 2016

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

“…12). In addition, xanthohumol has been reported to reduce the production of inflammatory mediators in LPS/ IFN-γ stimulated macrophages by down-regulation of Stat1α and IRF-1 mRNA expression [66].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of TGF-β signaling, vasculogenic mimicry and proinflammatory gene expression by isoxanthohumol

et al. 2011

View full text Add to dashboard Cite

Differential anti-inflammatory pathway by xanthohumol in IFN-γ and LPS-activated macrophages

Cited by 87 publications

References 35 publications

Newly Synthesized ‘Hidabeni’ Chalcone Derivatives Potently Suppress LPS-Induced NO Production <i>via</i> Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

Newly Synthesized ‘Hidabeni’ Chalcone Derivatives Potently Suppress LPS-Induced NO Production <i>via</i> Inhibition of STAT1, but Not NF-κB, JNK, and p38, Pathways in Microglia

Effect of blending HA-g-PLLA on xanthohumol-loaded PLGA fiber membrane

Inhibition of TGF-β signaling, vasculogenic mimicry and proinflammatory gene expression by isoxanthohumol

Contact Info

Product

Resources

About