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Effects of Jatrorrhizine on inflammatory response induced by H2O2 in microglia by regulating the MAPK/NF-κB/NLRP3 signaling pathway

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Abstract

Microglia-induced neuroinflammation is a contributing factor to neurodegenerative diseases. Jatrorrhizine (JAT), an alkaloid isolated from Huanglian, has been shown to have neuroprotective effects against various neurodegenerative diseases, but its impact on microglia-induced neuroinflammation remains unclear. In this study, we investigated the role of JAT in MAPK/NF-κB/NLRP3 signaling pathway in an H2O2-induced oxidative stress model using microglia (N9 cells). We divided cells into six groups, including control, JAT, H2O2, H2O2 + 5 μmol/L JAT, H2O2 + 10 μmol/L JAT, and H2O2 + 20 μmol/L minocycline groups. Cell viability was measured using MTT assay and TNF-α levels were detected with an ELISA Kit. Western blot was used to detect NLRP3, HMGB1, NF-κB, p-NF-κB, ERK, p-ERK, p38, p-p38, p-JNK, JNK, IL-1β, and IL-18 expressions. Our results showed that JAT intervention improved H2O2-induced cytotoxicity in N9 cells and reduced the elevated expression of TNF-α, IL-1β, IL-18, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-p65/p65, NLRP3, and HMGB1 in H2O2 group. Furthermore, treatment with ERK inhibitor SCH772984 specifically blocked ERK phosphorylation, resulting in decreased protein levels of p-NF-κB, NLRP3, IL-1β, and IL-18 in H2O2 group. These results suggest that the MAPK/NF-κB signaling pathway may regulate the protein levels of NLRP3. Overall, our study indicates that JAT may have a protective effect on H2O2-treated microglia via inhibition the MAPK/NF-κB/NLRP3 pathway and could be a potential therapeutic approach for neurodegenerative diseases.

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Funding

This work was supported by Natural Science Foundation of Guangdong Province (No.2020A1515010580, 2021A1515011516, 2015A030313066), Science and Technology Planning Project of Guangzhou (No. 202102080239), National Natural Science Foundation of China (No. 81501093), Science and Technology Planning Project of Guangdong Province (No. 2014A020212622).

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Sheng Wang, Cai-Li Xu, Tao Luo & Hua-Qiao Wang

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  1. Sheng Wang
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  2. Cai-Li Xu
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  3. Tao Luo
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Conceptualization: Sheng Wang, Tao Luo, and Hua-Qiao Wang; data curation: Sheng Wang and Cai-Li Xu; formal analysis: Sheng Wang, Cai-Li Xu; funding acquisition: Tao Luo and Hua-Qiao Wang; investigation: Sheng Wang; methodology: Sheng Wang; supervision: Tao Luo and Hua-Qiao Wang; writing–original draft: Sheng Wang; writing – review & editing: Tao Luo. All authors read and approved the final manuscript.

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Correspondence to Tao Luo or Hua-Qiao Wang.

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Wang, S., Xu, CL., Luo, T. et al. Effects of Jatrorrhizine on inflammatory response induced by H2O2 in microglia by regulating the MAPK/NF-κB/NLRP3 signaling pathway. Mol Neurobiol 60, 5725–5737 (2023). https://doi.org/10.1007/s12035-023-03385-w

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