Preventive effects of arctigenin from Arctium lappa L against LPS-induced neuroinflammation and cognitive impairments in mice.

Abstract

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aβ) generation and the levels of amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.

• Authors: Quan Yuan, Yiran Wu, Gang Wang, Xiang Zhou, Xiaohui Dong, Zihan Lou, Sanqiang Li, Dongmei Wang
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 37 Issue 6 Pg. 2039-2052 (08 2022) ISSN: 1573-7365 [Electronic] United States
• PMID: 35731324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Amyloid beta-Protein Precursor
• Furans
• Lignans
• Lipopolysaccharides
• NF-kappa B
• Toll-Like Receptor 4
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• arctigenin

Topics

• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Arctium (metabolism)
• Aspartic Acid Endopeptidases (metabolism)
• Cognitive Dysfunction (chemically induced, drug therapy, prevention & control)
• Furans
• Inflammation (chemically induced, drug therapy, prevention & control)
• Lignans (pharmacology, therapeutic use)
• Lipopolysaccharides (pharmacology)
• Memory Disorders (metabolism)
• Mice
• Microglia (metabolism)
• NF-kappa B (metabolism)
• Neuroinflammatory Diseases
• Toll-Like Receptor 4 (metabolism)