Hydroxy-safflor yellow A attenuates Aβ1-42-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway

Zhang, Zuo-hui; Yu, Liu; Hui, Xinchen; Wu, Ze; Yin, Kang; Yang, Hui; Xu, Yun

doi:10.1016/j.brainres.2014.03.036

Cited by 92 publications

(56 citation statements)

References 23 publications

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“…We think this could be a mechanism for our observed beneficial effect of Ani/Neo combination on CS in this study. Furthermore, our study also showed that α7nAChR activation by the combined Ani/Neo application could produce anti-inflammation via JAK2-STAT3 activation293031, which was attested by the reduction of the levels of TNFα and IL-6 in the crushed muscle. The anti-inflammation lead to better survival of skeletal muscle fibers during and after CS.…”

Section: Discussionsupporting

confidence: 60%

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Shao

Peng

et al. 2016

Sci Rep

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Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 60%

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Shao

Peng

et al. 2016

Sci Rep

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“…Time course differences in the nuclear translocation of p65 and STAT3 in response to propofol, combined with the results of our STAT3 inhibitor or knockdown studies may be indicative of distinct roles for NFκB either in the preservation of nuclear levels of STAT3, or the prevention of sustained STAT3 activation in our model 16 , 23 . Whether propofol stimulates the NFκB and STAT3 pathways to act in synergism or antagonize each other’s function remains unknown and requires clarification.…”

Section: Discussionmentioning

confidence: 73%

“…Although it is activated in the presence of inflammatory stimuli such as tumor necrosis factor α (TNFα) to transcribe pro-inflammatory genes, it has also been shown to increase transcription of cell survival genes, including Bcl-2 15 . Inhibition of STAT3 has been shown to reverse the inactivation of the p65 subunit of NFκB 16 . NFκB functionally could ensure STAT3 nuclear retention or prevent sustained STAT3 activation to enhance cell survival.…”

Section: Introductionmentioning

confidence: 99%

Propofol mediates signal transducer and activator of transcription 3 activation and crosstalk with phosphoinositide 3-kinase/AKT

et al. 2014

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We previously demonstrated that propofol, an intravenous anesthetic with anti-oxidative properties, activated the phosphoinositide 3-kinase (PI3K)/AKT pathway to increase the expression of B cell lymphoma (Bcl)-2 and, therefore the anti-apoptotic potential on cardiomyocytes. Here, we wanted to determine if propofol can also activate the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway, another branch of cardioprotective signaling. The cellular response of nuclear factor kappa B (NFκB) and STAT3 was also evaluated. Cardiac H9c2 cells were treated by propofol alone or in combination with pretreatment by inhibitors for JAK2/STAT3 or PI3K/AKT pathway. STAT3 and AKT phosphorylation, and STAT3 translocation were measured by western blotting and immunofluorescence staining, respectively. Propofol treatment significantly increased STAT3 phosphorylation at both tyrosine 705 and serine 727 residues. Sustained early phosphorylation of STAT3 was observed with 25~75 μM propofol at 10 and 30 min. Nuclear translocation of STAT3 was seen at 4 h after treatment with 50 μM propofol. In cultured H9c2 cells, we further demonstrated that propofol-induced STAT3 phosphorylation was reduced by pretreatment with PI3K/AKT pathway inhibitors wortmannin or API-2. Conversely, pretreatment with JAK2/STAT3 pathway inhibitor AG490 or stattic inhibited propofol-induced AKT phosphorylation. In addition, propofol induced NFκB p65 subunit perinuclear translocation. Inhibition or knockdown of STAT3 was associated with increased levels of the NFκB p65 subunit. Our results suggest that propofol induces an adaptive response by dual activation and crosstalk of cytoprotective PI3K/AKT and JAK2/STAT3 pathways. Rationale to apply propofol clinically as a preemptive cardioprotectant during cardiac surgery is supported by our findings.

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“…4C). Similarly, NF-κB activation could lead to the activation of various pro-inflammatory markers that are implicated in neuronal degeneration37. The levels of activated inflammatory markers such as inducible nitric oxide synthase (iNOS) were analyzed in Aβ 1-42 -treated brains via western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice

Amin

Shah

Kim

2017

Sci Rep

159

115

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Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer’s disease (AD). The aims of the present study were to determine and explore the antioxidant nature and potential mechanism of vanillic acid (VA) in Aβ1-42-induced oxidative stress and neuroinflammation mediated cognitive impairment in mice. An intracerebroventricular (i.c.v.) injection of Aβ1-42 into the mouse brain triggered increased reactive oxygen species (ROS) levels, neuroinflammation, synaptic deficits, memory impairment, and neurodegeneration. In contrast, the i.p. (intraperitoneal) administration of VA (30 mg/kg, for 3 weeks) after Aβ1-42-injection enhanced glutathione levels (GSH) and abrogated ROS generation accompanied by an induction of the endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) via the activation of Akt and glycogen synthase kinase 3β (GSK-3β) in the brain mice. Additionally, VA treatment decreased Aβ1-42-induced neuronal apoptosis and neuroinflammation and improved synaptic and cognitive deficits. Moreover, VA was nontoxic to HT22 cells and increased cell viability after Aβ1-42 exposure. To our knowledge, this study is the first to reveal the neuroprotective effect of VA against Aβ1-42-induced neurotoxicity. Our findings demonstrate that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.

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Hydroxy-safflor yellow A attenuates Aβ1-42-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway

Cited by 92 publications

References 23 publications

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

Propofol mediates signal transducer and activator of transcription 3 activation and crosstalk with phosphoinositide 3-kinase/AKT

Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice

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