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Eburicoic acid from Laetiporus sulphureus (Bull.:Fr.) Murrill attenuates inflammatory responses through inhibiting LPS-induced activation of PI3K/Akt/mTOR/NF-κB pathways in RAW264.7 cells

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Abstract

Excessive activation of macrophages has been implicated in various types of inflammatory injury. Suppression of macrophage activation would have therapeutic benefits, leading to the alleviation of the progression of inflammatory diseases. Eburicoic acid (EA) is one of main bioactive components isolated from Laetiporus sulphureus (Bull.:Fr.) Murrill. In our previous study, we found that EA possessed anti-inflammatory activities. However, the cellular and molecular mechanisms underlying its anti-inflammatory activities remain to be poorly understood. The present study aimed to further evaluate its effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells. We investigated the anti-inflammatory effect by modulating LPS-induced activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/nuclear transcription factor-κB (NF-κB) pathway in RAW264.7 cells. The results showed that EA caused no obvious cytotoxicity, and its suitable concentrations on RAW264.7 cells were in the range from 0.02 to 0.08 μM. EA significantly inhibited the releases of inflammatory mediators, nitrite oxide (NO) and prostaglandin E2 (PGE2); suppressed mRNA and protein expression levels of inducible nitrite oxide synthase (iNOS) and cyclooxygenase-2 COX-2 and pro-inflammatory cytokine TNF-α, IL-6, and IL-1β; and reduced levels of phosphorylated PI3K, Akt, mTOR, and NF-κBp65 in LPS-induced RAW264.7 cells in dose- and time-dependent manners. These aforementioned results indicated that EA executed anti-inflammatory effect on LPS-induced RAW264.7 cells, and this effect might be achieved via suppressing the PI3K/Akt/mTOR/NF-κB signaling pathway and inhibiting the LPS-induced productions of inflammatory mediators and pro-inflammatory cytokines.

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Acknowledgments

This study was supported by the Common Projects from the National Natural Science Foundation of China (no. 31370373), National Drug Modernization Engineering Technology Research Center Foundation of Hubei Province (no. 20152Y007), and College of Biotechnology and Pharmaceutical Research Foundation of China Three Gorges University (no. Hy1402). We thanked Professor Chengfu Yuan for his valuable comments and suggestions for the revision of this paper.

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  1. Junzhi Wang and Pan Zhang are co-first authors.

    Junzhi Wang and Pan Zhang contributed equally to this work.

Authors and Affiliations

  1. Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei, 443002, China

    Junzhi Wang, Pan Zhang, Haibo He, Xinxin Se, Wenjun Sun, Beiyan Chen, Lin Zhang, Ximing Yan & Kun Zou

  2. Hubei Research Institute of Tujia Medicine, China Three Gorges University, Yichang, Hubei, China

    Junzhi Wang, Haibo He & Kun Zou

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  1. Junzhi Wang
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Wang, J., Zhang, P., He, H. et al. Eburicoic acid from Laetiporus sulphureus (Bull.:Fr.) Murrill attenuates inflammatory responses through inhibiting LPS-induced activation of PI3K/Akt/mTOR/NF-κB pathways in RAW264.7 cells. Naunyn-Schmiedeberg's Arch Pharmacol 390, 845–856 (2017). https://doi.org/10.1007/s00210-017-1382-3

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