Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling

Changcheng Lu; Chen Huang; Shuhui Qu; Huiyuan Lin; Hai-Jing Zhong; Cheong-Meng Chong

Biomedicine & Pharmacotherapy (Apr 2024)

Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling

Changcheng Lu,
Chen Huang,
Shuhui Qu,
Huiyuan Lin,
Hai-Jing Zhong,
Cheong-Meng Chong

Affiliations

Changcheng Lu: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao Special Administrative Region of China, China
Chen Huang: Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macao Special Administrative Region of China, China
Shuhui Qu: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao Special Administrative Region of China, China
Huiyuan Lin: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao Special Administrative Region of China, China
Hai-Jing Zhong: State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Correspondence to: State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Cheong-Meng Chong: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao Special Administrative Region of China, China; Correspondence to: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China, China.

Journal volume & issue: Vol. 173
p. 116379

Abstract

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Background: Microglia-mediated neuroinflammation is an important pathological feature in many neurological diseases; thus, suppressing microglial activation is considered a possible therapeutic strategy for reducing neuronal damage. Oxyimperatorin (OIMP) is a member of furanocoumarin, isolated from the medicinal herb Glehnia littoralis. However, it is unknown whether OIMP can suppress the neuroinflammation. Purpose: To investigate the neuroprotective activity of oxyimperatorin (OIMP) in LPS-induced neuroinflammation in vitro and in vivo models. Methods: In vitro inflammation-related assays were performed with OIMP in LPS-induced BV-2 microglia. In addition, intraperitoneal injection of LPS-induced microglial activation in the mouse brain was used to validate the anti-neuroinflammatory activity of OIMP. Results: OIMP was found to suppress LPS-induced neuroinflammation in vitro and in vivo. OIMP significantly attenuated LPS-induced the production of free radicals, inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines in BV-2 microglia without causing cytotoxicity. In addition, OIMP could reduce the M1 pro-inflammatory transition in LPS-stimulated BV-2 microglia. The mechanistic study revealed that OIMP inhibited LPS-induced NF-κB p65 phosphorylation and nuclear translocation. However, OIMP did not affect LPS-induced IκB phosphorylation and degradation. In addition, OIMP also was able to reduce LPS-induced microglial activation in mice brain. Conclusion: Our findings suggest that OIMP suppresses microglia activation and attenuates the production of pro-inflammatory mediators and cytokines via inhibition of NF-κB p65 signaling.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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