Isotrifoliol inhibits pro-inflammatory mediators by suppression of TLR/NF-κB and TLR/MAPK signaling in LPS-induced RAW264.7 cells

Li, Hua; Yoon, Ju-Duk; Won, Hyo-Jun; Ji, Hyeon-Seon; Yuk, Heong Joo; Park, Ki Hun; Park, Ho-Yong; Jeong, Tae‐Sook

doi:10.1016/j.intimp.2017.01.033

Cited by 63 publications

(46 citation statements)

References 43 publications

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“…LPS-stimutated degradation of IκB could be strongly inhibited by aspirin (Yang et al, 2014). Anti-inflammatory property is mediated by inhibition of several members of MAPK family, e.g., p38 MAPK and ERK1/2 (Jung et al, 2009;Li et al, 2017); according to recent data, aspirin enhances the inhibition of p38-MAPK and ERK phosphorylation in a microglial cell line (Yang et al, 2014). Cytokines are important to the normal and pathologic immunomodulatory functions of the microglia.…”

Section: Discussionmentioning

confidence: 96%

A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells

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Földesi

Feher³

et al. 2017

Brain Research Bulletin

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Aspirin, one of the most widely used non-steroidal anti-inflammatory drugs, has extensively studied effects on the cardiovascular system. To reveal further pleiotropic, beneficial effects of aspirin on a number of pro- and anti-inflammatory microglial mechanisms, we performed morphometric and functional studies relating to phagocytosis, pro- and anti-inflammatory cytokine production (IL-1β, tumor necrosis factor-α (TNF-α) and IL-10, respectively) and analyzed the expression of a number of inflammation-related genes, including those related to the above functions, in pure microglial cells. We examined the effects of aspirin (0.1mM and 1mM) in unchallenged (control) and bacterial lipopolysaccharide (LPS)-challenged secondary microglial cultures. Aspirin affected microglial morphology and functions in a dose-dependent manner as it inhibited LPS-elicited microglial activation by promoting ramification and the inhibition of phagocytosis in both concentrations. Remarkably, aspirin strongly reduced the pro-inflammatory IL-1β and TNF-α production, while it increased the anti-inflammatory IL-10 level in LPS-challenged cells. Moreover, aspirin differentially regulated the expression of a number of inflammation-related genes as it downregulated such pro-inflammatory genes as Nos2, Kng1, IL1β, Ptgs2 or Ccr1, while it upregulated some anti-inflammatory genes such as IL10, Csf2, Cxcl1, Ccl5 or Tgfb1. Thus, the use of aspirin could be beneficial for the prophylaxis of certain neurodegenerative disorders as it effectively ameliorates inflammation in the brain.

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Section: Discussionmentioning

confidence: 96%

A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells

Kata

Földesi

Feher³

et al. 2017

Brain Research Bulletin

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“…Toll-like receptor (TLR)-4 is a member of the TLR family, which serves a vital role in the innate immune system and may be activated by LPS ( 4 ). TLR4 and its associated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways have been demonstrated to be correlated with LPS-induced inflammation ( 5 , 6 ). An increased level of cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6, aggravates the development and progression of the septic myocardial dysfunction ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Glutamine ameliorates lipopolysaccharide‑induced cardiac dysfunction by regulating the toll‑like receptor 4/mitogen‑activated protein kinase/nuclear factor‑kB signaling pathway

Zhang

et al. 2017

Exp Ther Med

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The inflammatory response of sepsis induced by lipopolysaccharide (LPS) may result in irreversible cardiac dysfunction. Glutamine (GLN) has a multitude of pharmacological effects, including anti-inflammatory abilities. Previous studies have reported that GLN attenuated LPS-induced acute lung injury and intestinal mucosal injury. The present study investigated whether GLN exerts potential protective effects on LPS-induced cardiac dysfunction. Male Sprague-Dawley rats were divided into three groups (15 rats per group), including the control (saline-treated), LPS and LPS+GLN groups. Pretreatment with 1 g/kg GLN was provided via gavage for 5 days in the LPS+GLN group, while the control and LPS groups received the same volume of normal saline. On day 6, a cardiac dysfunction model was induced by administration of LPS (10 mg/kg). After 24 h, the cardiac functions of the rats that survived were detected by echocardiography and catheter-based measurements. The serum levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay, while the mRNA levels of toll-like receptor (TLR)4, TNF-α, IL-1β and IL-6 were examined by reverse transcription-quantitative polymerase chain reaction. The protein expression of TLR4, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were also determined by western blot analysis. The results of echocardiography and catheter-based measurements revealed that GLN treatment attenuated cardiac dysfunction. GLN treatment also attenuated the serum and mRNA levels of the pro-inflammatory cytokines. In addition, the protein levels of TLR4, phosphorylated (p-)extracellular signal-regulated kinase, p-c-Jun N-terminal kinase and p-P38 were reduced upon GLN pretreatment. Furthermore, GLN pretreatment resulted in decreased activation of the NF-κB signaling pathway. In conclusion, GLN has a potential therapeutic effect in the protection against cardiac dysfunction mediated by sepsis through regulating the TLR4/MAPK/NF-κB signaling pathway.

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“…Generally, the inactive form of the NF‐κB p65/p50 heterodimers associated with IκBα is sequestered in the cytoplasm, which prevents the translocation of NF‐κB to the nucleus, where it performs transcriptional regulation of genes. However, stimulation by inflammatory stimuli triggers the IKK‐mediated phosphorylation and degradation of IκBα, leading to the release of the NF‐κB complex and its translocation to the nucleus, which ultimately results in the transcription of inflammation‐related genes . In the present study, the effect of GBSP3a on the NF‐κB signaling pathway in RAW 264.7 cells was elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…During inflammation, a large number of macrophages are recruited, leading to the secretion of increased amounts of inflammatory mediators such as NO and prostaglandin E 2 (PGE 2 ) as well as pro‐inflammatory cytokines, including TNF‐α, interleukins (ILs) and interferon. The excessive production of inflammatory mediators by activated macrophages can cause cell and tissue damage and eventually chronic inflammation …”

Section: Introductionmentioning

confidence: 99%

Ginkgo biloba sarcotesta polysaccharide inhibits inflammatory responses through suppressing both NF‐κB and MAPK signaling pathway

Huang

et al. 2018

J Sci Food Agric

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BACKGROUND: Polysaccharides, common components of natural products extensively studied as dietary supplements and functional foods, have been found to have various activities. In the present study, a water-soluble polysaccharide, namely GBSP3a, was isolated and purified from G. biloba sarcotesta. The anti-inflammatory activity of GBSP3a in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and the potential underlying molecular mechanisms were then assessed. RESULTS: GBSP3a exerted its anti-inflammatory effect by remarkably inhibiting the secretion of pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin E 2 (PGE 2 ), tumor necrosis factor-(TNF-), interleukin-6 (IL-6) and interleukin-1 (IL-1 ) in LPS-stimulated RAW264.7 macrophages. Excessive mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose-dependently inhibited by GBSP3a in LPS-stimulated RAW264.7 cells. Further research suggested that the anti-inflammatory effect of GBSP3a can be attributed to the modulation of the NF-B and MAPK signaling pathways. CONCLUSION: GBSP3a exhibits anti-inflammatory activity and exerts its anti-inflammatory effect probably through suppressing both NF-B and MAPK signaling pathway, indicating that GBSP3a could be used for the development of anti-inflammatory agent or nutraceuticals. Statistical analysisAll results were from at least triplicate experiments and are presented as the mean ± standard deviation (SD). Statistical analysis was conducted using the SPSS 13.0 software (IBM Corp., Armonk, NY, USA). Analysis of significant difference was assessed by one-way analysis of variance (ANOVA), followed by the Duncan's multiple-range test. Statistical significance was set as P < 0.05. RESULTS Homogeneity, molecular weight and monosaccharide composition of GBSP3aAfter purification by gel filtration chromatography, GBSP3a was obtained as an off-white powder. It had no absorption at 280 or 260 nm in the UV spectrum and had a negative response to the Folin-phenol test and barium chloride test, indicating the absence of protein, nucleic acid and sulfated groups. The content of uronic acid in GBSP3a was 7.92% as detected by the meta-hydroxydiphenyl colorimetric method. 35 The HPGPC profile of GBSP3a (Fig. 1A) displays a single and symmetrical peak, indicating that GPSB3a is a homogeneous polysaccharide. The weight average molecular weight of GBSP3a, as determined by high-performance size exclusion chromatography, was J Sci Food Agric 2019; 99: 2329-2339 CONCLUSIONIn the present study, a water-soluble polysaccharide called GBSP3a was isolated from G. biloba sarcotesta. The anti-inflammatory activity of GBSP3a was then assessed in LPS-induced RAW264.7 macrophages. The results indicated that GBSP3a exerted its J Sci Food Agric 2019; 99: 2329-2339

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Isotrifoliol inhibits pro-inflammatory mediators by suppression of TLR/NF-κB and TLR/MAPK signaling in LPS-induced RAW264.7 cells

Cited by 63 publications

References 43 publications

A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells

A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells

Glutamine ameliorates lipopolysaccharide‑induced cardiac dysfunction by regulating the toll‑like receptor 4/mitogen‑activated protein kinase/nuclear factor‑kB signaling pathway

Ginkgo biloba sarcotesta polysaccharide inhibits inflammatory responses through suppressing both NF‐κB and MAPK signaling pathway

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