Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing NF-κB

Haishan Jiao; Jianping Jia

doi:10.1016/j.bbrc.2021.12.071

Ginsenoside compound K acts via LRP1 to alleviate Amyloid β₄₂-induced neuroinflammation in microglia by suppressing NF-κB

Biochem Biophys Res Commun. 2022 Jan 29:590:14-19. doi: 10.1016/j.bbrc.2021.12.071. Epub 2021 Dec 21.

Authors

Haishan Jiao¹, Jianping Jia²

Affiliations

¹ Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, 45 Changchun Street, Beijing, China.
² Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, 45 Changchun Street, Beijing, China; Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China; Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China; Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. Electronic address: jjp@ccmu.edu.cn.

PMID: 34968779
DOI: 10.1016/j.bbrc.2021.12.071

Abstract

Background: Alzheimer's disease (AD), has caused a mass of disability and mortality in elder populations, which increases global health burden. There are still limited effective disease-modifying drugs. Alleviating microglia-evoked neuroinflammation has become a promising treatment strategy for AD. Ginsenoside Compound K has been demonstrated to exhibit anti-inflammatory and neuroprotective benefits. Here we measured the effects of Ginsenoside Compound K in inhibiting amyloid-induced microglia inflammation and the possible molecular mechanisms and target of action in vitro.

Methods: The cytotoxicity of all chemical reagents on BV2 cells were evaluated using the MTT assay. qRT-PCR and ELISA were carried out to detect the inflammatory cytokines levels. Western blot was utilized to determine the effect of Ginsenoside Compound K on the nuclear factor-κB (NF-κB) p65 nuclear translocation. Antagonist Receptor Associated Protein (RAP) was used to verify the engagement of low-density lipoprotein receptor-related protein 1(LRP1).

Results: Ginsenoside Compound K diminished inflammatory cytokine production and reversed NF-κB p65 nuclear translocation induced by Aβ₄₂ oligomers. LRP1 expression was up-regulated by Ginsenoside Compound K. When LRP1 was blocked by antagonist RAP, the protective effect of Ginsenoside Compound K was massively eliminated.

Conclusion: These observations provide evidence for anti-inflammatory effect of Ginsenoside Compound K through NF-κB pathway via LRP1 activation, and support further evaluation of Ginsenoside Compound K as a potential effective modulator for AD.

Keywords: Alzheimer's disease; Amyloid β(42) oligomers; Ginsenoside compound K; LRP1; Microglia; Neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / toxicity*
Animals
Anti-Inflammatory Agents / pharmacology
Brain / pathology*
Cell Line
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Cytokines / biosynthesis
Ginsenosides / pharmacology*
Inflammation / pathology*
LDL-Receptor Related Protein-Associated Protein
Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
Mice
Microglia / drug effects
Microglia / metabolism
Microglia / pathology*
NF-kappa B / metabolism*
Transcription Factor RelA / metabolism

Substances

Amyloid beta-Peptides
Anti-Inflammatory Agents
Cytokines
Ginsenosides
LDL-Receptor Related Protein-Associated Protein
Low Density Lipoprotein Receptor-Related Protein-1
NF-kappa B
Transcription Factor RelA
ginsenoside M1