Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 × Tg-AD transgenic mice

Zhiwei Xu; Xiaojie Zhou; Xiao Hong; Sichen Wang; Jiale Wei; Junhao Huang; Liting Ji; Yuanxiao Yang; Thomas Efferth; Chunlan Hong; Changyu Li

doi:10.1016/j.phymed.2023.154695

Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 × Tg-AD transgenic mice

Phytomedicine. 2023 Apr:112:154695. doi: 10.1016/j.phymed.2023.154695. Epub 2023 Feb 7.

Authors

Zhiwei Xu¹, Xiaojie Zhou², Xiao Hong¹, Sichen Wang¹, Jiale Wei¹, Junhao Huang¹, Liting Ji¹, Yuanxiao Yang³, Thomas Efferth⁴, Chunlan Hong⁵, Changyu Li⁶

Affiliations

¹ School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
² Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
³ School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, China.
⁴ Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz 55128, Germany.
⁵ School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: chunlan.hong@outlook.com.
⁶ School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lcyzcmu@sina.com.

PMID: 36774844
DOI: 10.1016/j.phymed.2023.154695

Abstract

Background: Shi chang pu (Acorus tatarinowii Schott) is a herbal used in the treatment of Alzheimer's disease (AD) in China. The essential oil of Shi chang pu (SCP-oil) is the main active component. However, its effects on the neuroinflammation of AD have not been well studied.

Purpose: Neuroinflammation mediated by the NLRP3 inflammasome plays a crucial role in AD. This study was designed to evaluate the effect of SCP-oil on cognitive impairment of App_Swe/PSEN1_M146V/MAPT_P301L triple transgenic (3 × Tg-AD) mice model and investigate the mechanism underlying its anti-inflammation effects.

Methods: Thirty-two 3 × Tg-AD mice at 12 months and 8 wild-type B6 mice were used for this experiment. The 3 × Tg-AD mice were administered with SCP-oil or donepezil hydrochloride for 8 weeks. Morris water maze test and step-down test were used to evaluate the cognitive ability of mice. The pathological changes, neuroinflammation, and the NLRP3 inflammasome related-protein of AD mice were detected by histomorphological examination, TUNEL staining, immunofluorescence, immunohistochemistry, qRT-PCR, Elisa, and western blot assays.

Results: SCP-oil treatment attenuated cognitive dysfunction of 3 × Tg-AD mice. Moreover, SCP-oil also ameliorated characteristics pathological of AD, such as pathological changes damage, deposition of Aβ, phosphorylation of Tau, and neuronal loss. Additionally, SCP-oil treatment alleviated the neuroinflammation and inhibited phosphorylation of IKKβ, NF-κB, and NLRP3 inflammasome related-protein NLRP3, ASC, Caspase-1, cleaved-Caspase-1, and GSDMD-N in the hippocampus of 3 × Tg-AD mice.

Conclusion: Overall, SCP-oil contributed to neuroprotection in 3 × Tg-AD mice by reduced activation of NLRP3 inflammasome by inhibiting the NF-κB signaling pathway.

Keywords: Acorus tatarinowii; Alzheimer's disease; NLRP3 inflammasome; Neuroinflammation; Phytotherapy.

MeSH terms

Acorus*
Alzheimer Disease* / metabolism
Animals
Caspase 1 / metabolism
Inflammasomes / metabolism
Mice
Mice, Transgenic
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Neuroinflammatory Diseases
Oils, Volatile* / pharmacology
Oils, Volatile* / therapeutic use

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NF-kappa B
Oils, Volatile
Caspase 1
Nlrp3 protein, mouse