Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells

Wu, Fang; Zhang, Wei; Li, Lin; Zheng, Fenping; Shao, Xueting; Zhou, Jiaheng; Li, Hong

doi:10.1016/j.ejphar.2010.11.022

Cited by 33 publications

(22 citation statements)

References 25 publications

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“…1a, HBZY-1 cells exposed to ALA of different concentrations retained almost the same viability when compared with those cultured in normal medium, suggesting that ALA of concentration no more than 400 μM hardly affected the normal cell function. According to a previous reported study [21], LPS of 1 μg/mL was used to stimulate HBZY-1 cells. As indicated in Fig.…”

Section: Effects Of Ala On Hbzy-1 Cell Viability and The Expression Omentioning

confidence: 99%

Alpha-Lipoic Acid Exerts Anti-Inflammatory Effects on Lipopolysaccharide-Stimulated Rat Mesangial Cells via Inhibition of Nuclear Factor Kappa B (NF-κB) Signaling Pathway

Jia-hong

Zhao

et al. 2014

Inflammation

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Sepsis is often initiated by invasive infection, characterized by overwhelming induction of pro-inflammatory cytokines. The incidence and mortality of sepsis and the associated development of acute kidney injury (AKI) remain high, and lines of research into potential treatments are needed. This study was conducted to investigate effects of alpha-lipoic acid (ALA) on septic AKI in vitro. ALA of 200 or 400 μM was used to pretreat rat HBZY-1 mesangial cells before commencement of 1 μg/mL lipopolysaccharide (LPS). Our data indicated that ALA pretreatment reduced LPS-stimulated release of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 beta (IL-1β), as well as IL-6, in HBZY-1 cell supernatant. Moreover, LPS-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was inhibited by ALA pretreatment, and consequently, the secretion levels of their respective enzymatic products prostaglandin E2 (PGE2) and nitric oxide (NO) were significantly decreased. LPS-enhanced phosphorylation of nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα) and IκB kinase alpha/beta (IKKα/β) and nuclear translocation of NF-κB subunit p65 in HBZY-1 cells were inhibited by ALA pretreatment. Additionally, the NF-κB inhibitor N-acetylcysteine (NAC) exerted similar inhibitory effects as ALA on COX-2 and iNOS expression. In summary, our study demonstrates that ALA mitigates LPS-induced inflammatory responses in rat mesangial cells probably via inhibition of NF-κB signaling pathway, suggesting a therapeutic potential of ALA in AKI related to sepsis.

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Section: Effects Of Ala On Hbzy-1 Cell Viability and The Expression Omentioning

confidence: 99%

Alpha-Lipoic Acid Exerts Anti-Inflammatory Effects on Lipopolysaccharide-Stimulated Rat Mesangial Cells via Inhibition of Nuclear Factor Kappa B (NF-κB) Signaling Pathway

Jia-hong

Zhao

et al. 2014

Inflammation

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“…Accumulating evidence indicates that chronic inflammation plays a critical role in several chronic degenerative pathologies, including cardiovascular diseases, renal damage, and cancer [7,8]. Several anti-LPS or anti-cytokine clinical trials have been conducted, but none has so far been successful.…”

Section: Introductionmentioning

confidence: 99%

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells

Li¹,

Gao²,

Wu³

et al. 2015

ABBS

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Parthenolide (PTL) shows potent anti-inflammatory and anti-cancer activities. In the present study, the molecular mechanisms of PTL's activities were explored in lipopolysaccharide (LPS)-induced human leukemia monocytic THP-1 cells and human primary monocytes. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay was used to analyze the effect of PTL on THP-1 cell viability. Enzyme-linked immunosorbent assay was used to determine the effect of PTL on LPS-induced inflammatory cytokine secretion. Flow cytometry and quantitative real-time polymerase chain reaction were used to assess the effect of PTL on LPSinduced toll-like receptor 4 (TLR4) expression. Phosphorylation levels of signaling molecules were determined by western blot analysis. Results showed that PTL <12.5 μM did not significantly affect THP-1 cells viability. LPS treatment led to a marked up-regulation of interleukin (IL)-6, IL-1β, IL-8, IL-12p40, tumor necrosis factor-α, IL-18, and NO in THP-1 cells. However, PTL inhibited the expression of these cytokines in a dose-dependent manner, with IC 50 values of 1.091-2.620 μM. PTL blocked TLR4 expression with an IC 50 value of 1.373 μM as determined by the flow cytometry analysis, and this blocking effect was verified at both protein and mRNA levels. Up-regulation of phosphorylation levels of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, p38, nuclear factor κB (NF-κB) p65, and IκBα and up-regulation of expressions of other molecules (inducible nitric oxide synthase, TLR4, and TNF receptor-associated factor 6) induced by LPS were abolished by PTL in a dose-dependent manner. The anti-inflammatory mechanisms of PTL operate partly through the TLR4-mediated mitogen-activated protein kinase and NF-κB signaling pathways. Therefore, TLR4 may be a new target for anti-inflammation therapies.

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“…It has been shown to exert beneficial effects against neurological disorders, including Alzheimer's disease, Parkinson's disease, stroke, depression, and anxiety (Watanabe et al 1983;Maruyama et al 1998;Liu et al 2005;Chen et al 2011;Xu et al 2008;Chang-Mu et al 2010). Previous studies performed in our laboratory, as well as by others, had demonstrated anti-inflammatory effects of these compounds to mitigate production of ROS, iNOS/NO, and prostaglandins/leukotrienes in BV-2 microglial cells stimulated with LPS/IFNc Kuo et al 2010;Oh et al 2009;Wu et al 2011). The mechanism of action was suggested to involve inhibition of ERK1/2 phosphorylation, NADPH oxidase activation/translocation, and NFjB activation.…”

Section: Discussionmentioning

confidence: 88%

Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2

et al. 2016

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Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al. in J Neuroinflammation 12(1):199, 2015. doi: 10.1186/s12974-015-0419-0 ). In this study, we investigate the action of botanical compounds and assess whether suppression of cPLA2 in microglia is involved in the neurotoxic effects on neurons. Differentiated SH-SY5Y neuroblastoma cells were used to test the neurotoxicity of conditioned medium from stimulated microglial cells, and WST-1 assay was used to assess for the cell viability of SH-SY5Y cells. Botanicals such as quercetin and honokiol (but not cyanidin-3-O-glucoside, 3CG) were effective in inhibiting LPS-induced nitric oxide (NO) production and phosphorylation of cPLA2. Conditioned medium from BV-2 cells stimulated with LPS or IFNγ caused neurotoxicity to SH-SY5Y cells. Decrease in cell viability could be ameliorated by pharmacological inhibitors for cPLA2 as well as by down-regulating cPLA2 with siRNA. Botanicals effective in inhibition of LPS-induced NO and cPLA2 phosphorylation were also effective in ameliorating microglial-induced neurotoxicity. Results demonstrated cytotoxic factors from activated microglial cells to cause damaging effects to neurons and potential use of botanical polyphenols to ameliorate the neurotoxic effects.

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Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells

Cited by 33 publications

References 25 publications

Alpha-Lipoic Acid Exerts Anti-Inflammatory Effects on Lipopolysaccharide-Stimulated Rat Mesangial Cells via Inhibition of Nuclear Factor Kappa B (NF-κB) Signaling Pathway

Alpha-Lipoic Acid Exerts Anti-Inflammatory Effects on Lipopolysaccharide-Stimulated Rat Mesangial Cells via Inhibition of Nuclear Factor Kappa B (NF-κB) Signaling Pathway

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells

Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2

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