Ferulic acid produces neuroprotection against radiation-induced neuroinflammation by affecting NLRP3 inflammasome activation

Abstract

Purpose

After radiation therapy of brain tumors, radiation-induced cognitive impairment is a common and severe complication. Neuroinflammation mediated by microglia is a critical event that accelerates cognitive or functional decline. Ferulic acid (FA), a phenolic plant component, possesses multiple pharmacological effects, such as anti-inflammatory and anti-radiation. The current research attempts to ascertain the protection of FA on radiation-induced neuroinflammation and the mechanism of this effect.

Materials and methods

C57BL/6 mice were irradiated with ⁶⁰Co γ-ray to establish a brain injury model. The Morris water maze experiment was used to observe the effects of FA on the spatial learning and memory impairment of irradiated mice. The pathological changes of hippocampal tissue were observed by HE staining. Besides, microglia BV-2 cell lines were used to study the anti-neuroinflammatory impacts of FA on radiation-induced microglial activation and further elucidate the potential mechanisms influencing FA-mediated neuroprotective properties. The cell morphological changes were observed using an optical microscope. The cytotoxicity of FA and radiation to BV-2 cells was determined using the CCK-8 assay. Additionally, Western blot and quantitative real-time PCR detected the expression and transcription of NLRP3 inflammasome and pro-inflammatory cytokines in hippocampus and BV-2 cells.

Results

FA could enhance learning and memory capacity and ameliorate pathological changes in the hippocampal tissues of irradiated mice. The cell radiation injury model was established by 8 Gy ⁶⁰Co γ-ray, and the concentration of subsequent administration was determined to be 2.5, 5, and 10 μmol/L. Furthermore, FA could suppress the transcription and expression of NLRP3 in hippocampal tissue and microglia, and also the increased secretion of pro-inflammatory factors.

Conclusion

This study established that FA targeting the NLRP3 inflammasome has a neuroprotective effect against radiation-induced nerve damage, implying that FA might have some potential in the treatment of radiation-induced cognitive impairment.

Keywords:

• Radiation cognitive impairment
• neuroinflammation
• ferulic acid
• neuroprotection

Acknowledgments

BV-2 cells were donated by Pro. Wenxia Zhou from Beijing Institute of Pharmacology and Toxicology (Beijing, China).

Ethical approval

The animal experiments were conducted in compliance with Animal Ethics Committee’s guidelines (Ethics Number: IACUC-DWZX-2020-770). All animal experiments were conducted in compliance with the Guidelines of Chinese Animal Care and Welfare. This article contains no experiments involving human subjects conducted by any of the authors.

Author contributions

GL, YN, CSH, and GZ planned experiments. GL, XZ, and CKH performed experiments. ZL provided equipment. YG and ZM planed radiation treatment. GL and ZM analyzed data and wrote the paper.

Disclosure statement

The other authors declare that they do not have any conflicting interests.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (NO. 81873063) and Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (NO. ZYYCXTD-C-202009).

Notes on contributors

Guifang Liu

Guifang Liu, master, is a postgraduate jointly trained by School of Traditional Chinese Medicine, Guangdong Pharmaceutical University and Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Yao Nie

Yao Nie, master, is a student of Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Congshu Huang

Congshu Huang, master, is a postgraduate jointly trained by School of Traditional Chinese Medicine, Guangdong Pharmaceutical University and Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Guihua Zhu

Guihua Zhu, master, is a student of Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Xuemei Zhang

Xuemei Zhang, master, is a postgraduate jointly trained by School of Traditional Chinese Medicine, Guangdong Pharmaceutical University and Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Changkun Hu

Changkun Hu, master, is a student of Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Zhihui Li

Zhihui Li, experimenter, is an experimenter at Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Yue Gao

Yue Gao, PhD, is a Professor of Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.

Zengchun Ma

Zengchun Ma, PhD, is an associate professor of Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine.