A novel synthetic HTB derivative, BECT inhibits lipopolysaccharide-mediated inflammatory response by suppressing the p38 MAPK/JNK and NF-κB activation pathways

Kang, Seong-Mook; More, Sandeep Vasant; Park, Ju‐Young; Kim, Byungwook; In, Park Jeong; Yoon, Seo Hyun; Choi, Dong‐Kug

doi:10.1016/j.pharep.2013.08.015

Cited by 26 publications

(11 citation statements)

References 39 publications

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“…Microglia are found clustered around amyloid plaques where they phagocytize and degrade plaques as an integral part of clearance mechanism (El-Shimy et al, 2015). Activated microglial cells control the release of proinflammatory mediators through activation of the MAPK signaling pathways (Kang et al, 2014). The basic structure of MAPKs is comprised of serine/threonine protein kinases which execute and promote a large number of cellular functions in various cell types.…”

Section: Introductionmentioning

confidence: 99%

The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

Shah

Zhao

Hussain

et al. 2017

Front. Aging Neurosci.

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Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrP Sc ) in the brain. PrP Sc accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca 2+ ) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear. Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that rule the signaling of many extracellular stimuli from plasma membrane to the nucleus. However the identification of numerous points of cross talk between the UPR and MAPK signaling pathways may contribute to our understanding of the consequences of ER stress in prion diseases. Indeed the MAPK signaling network is known to regulate cell cycle progression and cell survival or death responses following a variety of stresses including misfolded protein response stress. In this article, we review the UPR signaling in prion diseases and discuss the triad of MAPK signaling pathways. We also describe the role played by MAPK signaling cascades in Alzheimer’s (AD) and Parkinson’s disease (PD). We will also overview the mechanisms of cell death and the role of MAPK signaling in prion disease progression and highlight potential avenues for therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

Shah

Zhao

Hussain

et al. 2017

Front. Aging Neurosci.

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“…The released κBp65 translocates into the nucleus, binding to the κBp65 on the DNA. The above reaction generates TNF-α mRNA and participate in the body's inflammatory responses (Kang et al, 2014;Kim et al, 2012). Our results indicate SMP pretreatment suppresses IĸBα kinase and p65 phosphorylation in LPS-induced hepatitis, which in turn inhibites the activation of NF-ĸB.…”

Section: Discussionmentioning

confidence: 63%

Salvia miltiorrhiza polysaccharides protect against lipopolysaccharide-induced liver injury by regulating NF-κb and Nrf2 pathway in mice

Han

Wei

Wang

et al. 2019

Food and Agricultural Immunology

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2019) Salvia miltiorrhiza polysaccharides protect against lipopolysaccharide-induced liver injury by regulating NF-κb and Nrf2 pathway in mice, Food and Agricultural Immunology, 30:1, 979-994, ABSTRACTThe current study was conducted to investigate the hepatoprotective effects of Salvia miltiorrhiza polysaccharides (SMP) against lipopolysaccharide (LPS) induced liver injury. The mice were treated with SMP first and LPS later. Results showed that SMPs significantly reduced the activities of serum alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), malondialdehyde (MDA) and contents of inflammation factors and mRNA expressions in LPS induced liver injury mice. However, SMP significantly increased the contents of glutathione (GSH), Superoxide dismutase (SOD) and Total antioxidant capacity (T-AOC). SMP also downregulated the expressions of p-p65, p-IκBα, inducible nitricoxide synthase (iNOS) and improved the expression of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Heme Oxygenase-1 (HO-1). The study indicates SMP protects the liver via attenuating inflammatory reactions and antioxidant effects.

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“…Limiting the production of neuroinflammatory mediators is crucial for neuronal protection and repair. Abnormal activation of the microglia and upregulation of pro-neuroinflammatory mediators are pathological features of neurodegenerative disorders (29)(30)(31). Furthermore, abnormal microglial accumulation and release of neuroinflammatory mediators is deleterious to neighboring neurons and may be related to neurodegenerative disease (32).…”

Section: Discussionmentioning

confidence: 99%

Petasites japonicus bakkenolide B inhibits lipopolysaccharide‑induced pro‑inflammatory cytokines via AMPK/Nrf2 induction in microglia

et al. 2017

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Abnormal neuroinflammatory responses have diverse roles in neuronal death, oxidative stress and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Microglia regulate these responses via molecular signaling cascades that involve inflammatory cytokines and complement proteins. Bakkenolide B from Petasites japonicus exhibits significant anti‑inflammatory and anti‑allergic bioactivities. The present study investigated the anti‑neuroinflammatory effects and underlying molecular mechanisms of bakkenolide B on the lipopolysaccharide (LPS)‑mediated neuroinflammatory response in microglia. The results indicated that bakkenolide B pretreatment significantly reduced microglial production of interleukin (IL)‑1β, IL‑6, IL‑12, and tumor necrosis factor (TNF)‑α. Furthermore, this effect was associated with reduced production of reactive oxygen species. The role of bakkenolide B was then evaluated in the upregulation of nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. The results suggested that bakkenolide B significantly upregulated Nrf2/ARE pathway‑related downstream factors, such as NADPH dehydrogenase quinone‑1 (NQO‑1) and heme oxygenase‑1 (HO‑1). Silencing of Nrf2, HO‑1 and NQO‑1 diminished the anti‑neuroinflammatory properties of bakkenolide B. AMP‑activated protein kinase (AMPK) activates the Nrf2/ARE signaling pathway, and the results of the present study demonstrated that bakkenolide B increased AMPK phosphorylation in microglia. In addition, an AMPK inhibitor abolished the bakkenolide B‑induced increase in nuclear Nrf2, NQO‑1 and HO‑1 protein expression. Finally, an AMPK inhibitor diminished the bakkenolide B‑mediated inhibition of LPS‑stimulated TNF‑α production. Taken together, the present results demonstrate that bakkenolide B may be an effective and therapeutically relevant AMPK/Nrf2 pathway activator for suppressing abnormal neuro-inflammation in neurodegenerative diseases.

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A novel synthetic HTB derivative, BECT inhibits lipopolysaccharide-mediated inflammatory response by suppressing the p38 MAPK/JNK and NF-κB activation pathways

Cited by 26 publications

References 39 publications

The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

Salvia miltiorrhiza polysaccharides protect against lipopolysaccharide-induced liver injury by regulating NF-κb and Nrf2 pathway in mice

Petasites japonicus bakkenolide B inhibits lipopolysaccharide‑induced pro‑inflammatory cytokines via AMPK/Nrf2 induction in microglia

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