The anti-inflammatory effect of 3-deoxysappanchalcone is mediated by inducing heme oxygenase-1 via activating the AKT/mTOR pathway in murine macrophages

Kim, Junhyeong; Choo, Young-Yeon; Tae, Nara; Min, Byung‐Sun; Lee, Jeong‐Hyung

doi:10.1016/j.intimp.2014.07.025

Cited by 32 publications

(24 citation statements)

References 35 publications

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“…mTOR is found downstream of the PI3K/Akt signal transduction, Akt phosphorylates mTOR, and the phosphorylated mTOR interacts with IKK to cause the activation of NF-κB. mTOR plays an important role in the LPS-induced inflammatory response, and the inhibition of mTOR reduces the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in the neutrophils [8,9,10,11,33]. Our experimental results show that the administration of SS-1 prior to induction with LPS can downregulate the signal transduction pathways triggered by the immune response in ALI tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Akt regulates LPS-induced NF-κB activation and promotes NF-κB phosphorylation via IκB kinase (IKK), thus enhancing the transcription ability of NF-κB [9]. Recent studies indicate that Akt also regulates mechanistic target of rapamycin (mTOR) activity, when mTOR binds to and phosphorylates IKK after being phosphorylated by Akt, thereby promoting the NF-κB activation [10]. On the contrary, the inhibition of mTOR reduces LPS-induced synthesis of pro-inflammatory cytokines and NF-κB phosphorylation, indicating that the PI3K/Akt/mTOR/IKK signal transduction pathways greatly affect the activation of NF-κB [8,9,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

Lin

Deng

Huang

et al. 2017

IJMS

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Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes Heme oxygenase 1 (HO-1) and Thioredoxin-1 (Trx-1) in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/nuclear factor erythroid-2-related factor Nrf2/Kelch Like ECH associated Protein 1 (Keap1) pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced ALI in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

Lin

Deng

Huang

et al. 2017

IJMS

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“…Since 3-DSC has been reported to elicit the activation of cell survival pathways (Kim et al ., 2014), we examined the effects of 3-DSC on growth of HDPCs. Analysis of real-time cell proliferation using xCELLigence system revealed that the proliferation of HDPCs was promoted by 3-DSC treatment in a concentration-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

Kim

Choi

Lee

et al. 2016

Biomolecules & Therapeutics

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3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of β-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/β-catenin and STAT signaling.

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“…9 This indicates that the route for PI3K/Akt/mTOR/IKK signal transduction has an essential impact on NF-kB activation.…”

Section: 9mentioning

confidence: 99%

“…Previous studies have shown that LPS causes phosphorylation of Akt through PI3K, and phosphorylated Akt promotes activation of the NF-kB and MAPK downstream signaling pathways through IKK, which regulates the release of proinammatory cytokines by the respiratory epithelium and maintains cell viability. 9,27,[29][30][31][32][33][34] Recent studies have implicated mTOR in the regulation of cell survival and immune responses. mTOR is downstream of PI3K/Akt during signal transduction.…”

Section: 33mentioning

confidence: 99%

Anti-inflammatory activity of Sanghuangporus sanghuang by suppressing the TLR4-mediated PI3K/AKT/mTOR/IKKβ signaling pathway

et al. 2017

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Sanghuangporus sanghuang (SS) is a mushroom that belongs to the genus Sanghuangporus and it is commonly called "Sangwhang" in Taiwan. It is popular in oriental countries and has been traditionally used as food and medicine. The mystery surrounding it was solved in 2012, when it was discovered. However, existing research has not extensively investigated the anti-inflammatory effect of sanghuang that grows on Morus trees. The aim of this study is to investigate the protective effects and underlying mechanism of SS on inflammation by lipopolysaccharide (LPS) induced in vitro and in vivo. Results showed that SS treatment markedly attenuated LPS-induced lung edema, by elevation of the levels of interleukin (IL)-1b, tumor necrosis factor (TNF)-a and IL-6 in bronchoalveolar lavage fluid (BALF) accompanied by a remarkable improvement of lung histopathological symptoms. Additionally, western blotting results suggest that anti-inflammatory effects of SS against the LPS-induced ALI may be due to its ability to inhibit the PI3K/Akt/mTOR/IKK, NF-kB and MAPK signaling pathways. Notably, our results suggest that SS suppresses LPS-induced ROS by inducing Nrf2 activation and HO-1, thioredoxin-1 expression in the lung tissues. Moreover, these findings suggest a potential application of SS in pulmonary inflammatory disease therapy.

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The anti-inflammatory effect of 3-deoxysappanchalcone is mediated by inducing heme oxygenase-1 via activating the AKT/mTOR pathway in murine macrophages

Cited by 32 publications

References 35 publications

Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

Anti-inflammatory activity of Sanghuangporus sanghuang by suppressing the TLR4-mediated PI3K/AKT/mTOR/IKKβ signaling pathway

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