Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways

Wang, Xiaoxiao; Wang, Chunming; Wang, Jiming; Zhao, Siqi; Zhang, Kuo; Wang, Jingmin; Zhang, Wei; Wu, Chunfu; Yang, Jingyu

doi:10.1016/j.neuropharm.2014.01.022

Cited by 115 publications

(76 citation statements)

References 90 publications

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“…A dedicated cyclase that makes epDM as its major product has not been reported before our work to our knowledge. Triterpene glycosides based on the DM and epDM skeletons have important pharmaceutical and antibacterial properties (44)(45)(46). Our results open up the possibility of manipulating both the nature of the precursor and the product specificity of the cyclization process for the production of diverse and novel triterpenes.…”

Section: Discussionmentioning

confidence: 85%

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Salmon

Thimmappa

Minto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.terpenes | natural products | plant defense | cyclization | mutants

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Section: Discussionmentioning

confidence: 85%

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Salmon

Thimmappa

Minto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been reported that suppressing Toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) results in inhibiting the translocation of nuclear factor (NF-B) and affecting the levels of inducible nitric oxide synthase (iNOS), NO, interleukin-1 beta (IL-1␤), IL-6 and tumor necrosis factor ␣ (TNF-␣) (Wang et al, 2014). Thus, TLR4/MyD88 signal pathway is very important for regulating inflammation.…”

Section: Introductionmentioning

confidence: 99%

Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation

Zhang

Yin

Tao

et al. 2016

Environmental Toxicology and Pharmacology

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“…A large number of studies have demonstrated that AKT, NF-κB and mitogen-activated protein kinases (MAPKs) play an important role in regulating the production of pro-inflammatory mediators in activated microglia [26,27,28]. In order to clarify the anti-inflammatory mechanism of TBMS1, we investigated the effects of TBMS1 on LPS-induced phosphorylation of NF-κB p65, AKT, p38, ERK1/2 and JNK1/2 in BV-2 cells.…”

Section: Resultsmentioning

confidence: 99%

Tubeimoside I Protects Dopaminergic Neurons Against Inflammation-Mediated Damage in Lipopolysaccharide (LPS)-Evoked Model of Parkinson’s Disease in Rats

Huang

et al. 2018

IJMS

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Parkinson’s disease (PD), a frequent degenerative disease in the elderly, is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc). Neuroinflammation caused by over-activated microglia plays a crucial role in the pathogenesis of PD. Tubeimoside I (TBMS1) has a broad anti-inflammatory effect in peripheral tissues, but the effect on neuroinflammation has not been reported. Therefore, we explored whether TBMS1 could protect dopaminergic neurons by inhibiting the activation of microglia in lipopolysaccharide (LPS)-induced PD rat model. In addition, then, the effect and mechanism of TBMS1 on neuroinflammation were assessed in LPS-exposed murine microglial BV-2 cells. The results in vivo showed that TBMS1 suppressed microglial activation and dopaminergic neurons’ reduction in LPS-injected PD rat model. In vitro study found that TBMS1 could inhibit LPS-induced inflammatory responses in BV-2 cells, and this effect was mediated by suppressing the phosphorylation of protein kinase B (AKT), nuclear factor-kappa B (NF-κB p65), p38 and extracellular regulated protein kinases (ERK1/2). Taken together, these results demonstrated for the first time that TBMS1 played a role in protecting dopaminergic neurons by inhibiting neuroinflammation mediated by microglia.

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Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways

Cited by 115 publications

References 90 publications

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation

Tubeimoside I Protects Dopaminergic Neurons Against Inflammation-Mediated Damage in Lipopolysaccharide (LPS)-Evoked Model of Parkinson’s Disease in Rats

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