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Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway

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Abstract

Objective

The currently available anti-inflammatory drugs often cause diverse side effects with long-term use. Exploring anti-inflammatory drugs with better efficacy and lower toxicity presents an ongoing challenge. Aloperine is an alkaloid extracted from the leaves and seeds of Sophora alopecuroides L. However, the anti-inflammatory effects of Aloperine have not been fully elucidated. This study aimed to investigate whether Aloperine suppresses lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages.

Methods

RAW264.7 macrophages were stimulated with LPS (1 μg/mL) in the presence or absence of Aloperine (50 and 100 μM). mRNA expression was measured by real-time PCR, and protein expression was assessed by western blot analysis. The secretion of pro-inflammatory cytokines was measured by ELISA. The levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured by staining. The transcriptional activity of NF-κB was assayed by a luciferase activity assay.

Results

The results proved that Aloperine inhibited the expression of LPS-induced pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17A (IL-17A)] in macrophages. Treatment with Aloperine inhibited NO production through suppressing inducible nitric oxide synthase (iNOS) expression and the secretion of prostaglandin E2 (PGE2) by inhibiting cyclooxygenase 2 (COX-2) expression. Aloperine prevented LPS-induced oxidative stress by reducing the generation of ROS. Furthermore, aloperine significantly reduced Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd-88) levels and prevented the nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated macrophages.

Conclusion

Taken together, our findings show that Aloperine could suppress LPS-induced macrophage activation by inhibiting the TLR4/Myd-88/NF-κB pathway.

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Acknowledgements

Key research fund of wannan medical college (WK2018ZF05).

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Authors and Affiliations

  1. Department of Nephrology, Yijishan Hospital of Wannan Medical College, # 92 Zheshan Road, Wuhu, 241002, Anhui Province, People’s Republic of China

    Yinyin Ye, Yuwei Wang & Yanlang Yang

  2. Medical Emergency Center, #158 Yueming Road, Baoshan District, Shanghai, 201900, People’s Republic of China

    Liangfei Tao

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  1. Yinyin Ye
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  2. Yuwei Wang
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Ye, Y., Wang, Y., Yang, Y. et al. Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway. Inflamm. Res. 69, 375–383 (2020). https://doi.org/10.1007/s00011-019-01313-0

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  • DOI: https://doi.org/10.1007/s00011-019-01313-0

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