Micheliolide attenuates neuroinflammation to improve cognitive impairment of Alzheimer's disease by inhibiting NF-κB and PI3K/Akt signaling pathways

Guizhen Yang; You Hu; Xiangyang Qin; Jinxia Sun; Zhulei Miao; Lixin Wang; Zunji Ke; Yuejuan Zheng

doi:10.1016/j.heliyon.2023.e17848

Micheliolide attenuates neuroinflammation to improve cognitive impairment of Alzheimer's disease by inhibiting NF-κB and PI3K/Akt signaling pathways

Heliyon. 2023 Jul 4;9(7):e17848. doi: 10.1016/j.heliyon.2023.e17848. eCollection 2023 Jul.

Authors

Guizhen Yang^{1

2

3}, You Hu^{1

3}, Xiangyang Qin⁴, Jinxia Sun^{2

3}, Zhulei Miao^{2

3}, Lixin Wang^{2

3}, Zunji Ke⁵, Yuejuan Zheng^{1

3}

Affiliations

¹ The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosafety, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
² Department of Immunology and Microbiology, School of Basic Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
³ Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ Department of Chemistry, School of Pharmacy, Air Force Medical University, Xi'an, Shaanxi, 710032, China.
⁵ Institute of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Abstract

Inflammatory reaction in the brain activates glial cells, and over-activated glial cells secrete inflammatory mediators, which aggravates the inflammatory response in the brain and accelerates the development of Alzheimer's disease (AD) in turn. Numerous natural compounds from herbs can alleviate inflammation, and it is very promising to find anti-neuroinflammatory natural compounds. Micheliolide (MCL) is an asesquiterpene lactone. Studies have proved that MCL showed an obvious anti-inflammatory property. Nevertheless, whether MCL can treat AD has not been determined. In this research, AD model mice were fed with a diet supplemented MCL for 3 months, the cognitive ability and inflammatory state of mice were detected. We found that MCL raised the frequency of touching novel objects, cut down the escape latency, raised the number of crossing platform, inhibited the infiltration of inflammatory cells and the secretion of interleukin-1α (IL-1α), IL-12p40, IL-13, IL-17A, tumor necrosis factor-α (TNF-α), granulocyte colony stimulating factor (G-CSF), macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) in peripheral blood samples, inhibited the hyperplasia of glial cells and the production of IL-1α, IL-4, G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), MIP-1α and MIP-1β, and reduced the deposition of Aβ peptides in the brain of AD mice. We also concluded that MCL dropped the expression of IL-1β, TNF-α, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the phosphorylation of IκB, p65 and Akt in BV-2 cells. In conclusion, MCL alleviates the intensity of systemic inflammatory reaction via inhibiting nuclear transcription factor κ gene binding (NF-κB) and phosphoinositide-3-kinase/serine/threonine kinase (PI3K/Akt) pathways in glial cells, and improves the cognitive impairment of AD mice. Therefore, MCL could be a therapeutic candidate for AD.

Keywords: Alzheimer's disease; Glial cells; Micheliolide; NF-κB; Neuro-inflammation; PI3K/Akt.