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CC BY 4.0 · Chinese medicine and natural products 2023; 03(03): e126-e132
DOI: 10.1055/s-0043-1773797
Original Article

Effect of Formononetin on Lipopolysaccharide-Induced Depressive-Like Behaviors and Neuroinflammation in Mice

Mengyuan Li
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
2   College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Hui Liu
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
2   College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Shuaijun Peng
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
2   College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Pan Su
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Erping Xu
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Ming Bai
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
,
Yucheng Li
1   Henan Key Laboratory for Modern Research on Zhang Zhongjing's Prescriptions, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (81973739, 82274496), Henan Province Outstanding Youth Science Foundation (202300410249).
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Abstract

Objective The objective of this article is to explore the effect of formononetin (FMN) on depressive-like behaviors and neuroinflammation in lipopolysaccharide (LPS)-induced mice.

Methods After acclimatization, male Institute of Cancer Research mice were randomly divided into normal group, LPS group, paroxetine group (20 mg/kg), FMN low-dose group (20 mg/kg, FMN20), and FMN high-dose group (40 mg/kg, FMN40), with eight mice in each group. The depressive-like behaviors were observed by sucrose preference test, tail suspension test (TST), and open field test. The protein and mRNA levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the hippocampus were determined by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The expression level of ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampus was observed by immunofluorescence staining to evaluate the activation level of microglia.

Results Compared with the control group, the sucrose preference rate, the activity time of the central area, the distance of the central area, and the number of times of entering the central area were significantly decreased in the LPS group (p < 0.01), and the immobility time of TST was significantly prolonged (p < 0.05), the expression levels of IL-6, IL-1β, and TNF-α protein and mRNA in hippocampus were significantly increased (p < 0.01), and the fluorescence intensity of Iba-1 in CA1, CA3, and DG regions of hippocampus was significantly increased (p < 0.01). Compared with the LPS group, the sucrose preference rate, central area activity time, central area activity distance, and the number of times of entering the central area were significantly increased (p < 0.05 or p <0.01) in the FMN group, and TST immobility time was significantly shortened (p < 0.01), the expression levels of IL-6, IL-1β, and TNF-α protein and mRNA in the hippocampus were significantly decreased (p < 0.05 or p < 0.01), and the fluorescence intensity of Iba-1 in CA1, CA3, and DG regions of hippocampus was significantly decreased (p < 0.01).

Conclusion FMN could inhibit LPS-induced activation of microglia, reduce hippocampal neuroinflammation, and improve depressive-like behaviors in mice.

Keywords

formononetin - depression - LPS - neuroinflammation - proinflammatory cytokines - activation of microglia

CRediT Authorship Contribution Statement

M.L. was responsible for conceptualization, data curation, validation, and writing original draft. H.L. was responsible for methodology, and investigation. S.P. was responsible for methodology, and supervision. E.X. was responsible for project administration and funding acquisition. M.B. was responsible for validation. Y.L. was responsible for project administration, conceptualization, supervision, and funding acquisition.




Publication History

Received: 21 February 2023

Accepted: 10 April 2023

Article published online:
27 September 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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