Anti-inflammatory effects of β-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway

Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Lee, Kyoungtae; Lee, Hak‐Ju; Choi, Yung Hyun; Jeong, Jin‐Woo; Kim, Gi‐Young

doi:10.1016/j.fct.2013.12.011

Cited by 52 publications

(34 citation statements)

References 32 publications

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“…Nrf2 directly affects the homeostasis of ROS and RNS by regulating the antioxidant defense systems through inducing the expression of Phase II enzyme genes, such as HO-1, GCL, and GPx. Various reports support the view that HO-1 induction results in the downregulation of inflammatory responses [9, 23, 31, 32]. Current data reveal that ME stimulates mRNA and protein expression of HO-1.…”

Section: Discussionsupporting

confidence: 56%

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract ofSolanum integrifoliumPoir.

Wang

Chiou

Shen

et al. 2014

BioMed Research International

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The green fruit of Solanum integrifolium Poir. has been used traditionally as an anti-inflammatory and analgesic remedy in Taiwanese aboriginal medicine. The goal of this study is to evaluate the anti-inflammatory activity and mechanism of the green fruit extract of S. integrifolium. A bioactivity-guided fractionation procedure was developed to identify the active partition fraction. The methanol fraction (ME), with the highest phenolic content, exhibited the strongest inhibitory effect against LPS-mediated nitric oxide (NO) release and cytotoxicity in RAW264.7 macrophages. ME also significantly downregulated the expression of LPS-induced proinflammatory genes, such as iNOS, COX-2, IL-1β, IL-6, CCL2/MCP-1, and CCL3/MIP1α. Moreover, ME significantly upregulated HO-1 expression and stimulated the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with the HO-1 inhibitor zinc protoporphyrin and MEK/ERK inhibitor U0126 attenuated ME's inhibitory activity against LPS-induced NO production. Taken together, this is the first study to demonstrate the anti-inflammatory activity of green fruit extract of S. integrifolium and its activity may be mediated by the upregulation of HO-1 expression and activation of ERK1/2 pathway.

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Section: Discussionsupporting

confidence: 56%

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract ofSolanum integrifoliumPoir.

Wang

Chiou

Shen

et al. 2014

BioMed Research International

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“…BV-2 cells, derived from primary mouse microglia cells, are considered as a reasonable model for in vitro pharmacological studies, since their response to LPS showed a similar pattern to primary microglia in vivo based on transcriptome and proteome analysis [26]. With respective to neurodegeneration studies, activated BV-2 cells by LPS secret pro-inflammatory cytokines, which have been shown to promote neuronal injury at high level [27]. This led us to evaluate the inhibitory effect of MME on inflammation using BV-2 cells, and we further investigated the possible molecular mechanisms underlying its anti-inflammatory action on cultured BV-2 cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells

Kim

Lee

et al. 2014

BMC Complement Altern Med

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BackgroundExcessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells.MethodsThe levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively.ResultsMME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy.ConclusionsThese results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways.

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“…In addition, other singling pathways are involved in beta-HIVSmediated tumor cell death as well [15,[24][25][26][27]. Early in 1999, Hashimoto et al had reported that beta-HIVS was able to activate caspase-3 in its anti-neoplastic effect [15].…”

Section: Discussionmentioning

confidence: 99%

Beta-Hydroxyisovalerylshikonin Inhibits the Growth of U266 Multiple Myeloma Cells by Triggering the Mitochondrial Pathway

Chen¹

2014

J Leuk

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Anti-inflammatory effects of β-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway

Cited by 52 publications

References 32 publications

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract ofSolanum integrifoliumPoir.

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract ofSolanum integrifoliumPoir.

Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells

Beta-Hydroxyisovalerylshikonin Inhibits the Growth of U266 Multiple Myeloma Cells by Triggering the Mitochondrial Pathway

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