Curcuma wenyujin extract alleviates cognitive deficits and restrains pyroptosis through PINK1/Parkin mediated autophagy in Alzheimer's disease

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-02-07 DOI:10.1016/j.phymed.2025.156482

Yu Qi , Jingwen Zhang , Yuanlong Zhang , Haoyun Zhu , Jiabao Wang , Xiao Xu , Shengjie Jin , Chunlai Wang , Fang Zhang , Min Zhao , Zhigang Wu , Haoru Zhu , Pengcheng Yan

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引用次数: 0

Abstract

Background

Pyroptosis and mitophagy have gained significant attention in Alzheimer's disease (AD) treatment. Curcumae Radix (CR), the dried radix of Curcuma wenyujin Y. H. Chen et C. Ling, is a traditional Chinese medicine (TCM) extensively utilized for neurological disorders. Yet, its impact and mechanistic role in AD remain unclear.

Purpose

This study aims to explore the active fraction of CR in AD treatment and its potential mechanisms.

Methods

CR extracts were qualitatively analyzed using UHPLC-Triple-TOF/MS. Aβ_1–42-induced mice received daily intragastric drug treatments for three weeks. Cognitive abilities of AD model mice were assessed through Y maze, novel object recognition, and eight-arm maze tests. Therapeutic targets of CR extracts were identified using quantitative proteomics. In both in vivo and in vitro settings, effects on pyroptosis and mitophagy were examined by Western blot (WB), immunofluorescence (IF) staining, and ELISA assays.

Results

The ethyl acetate (EAC) fraction of CR extract exhibited optimal anti-AD effects. CR extracts enhanced memory and cognition in Aβ_1–42-induced mice, improved neuronal morphology, and reduced Aβ accumulation in the brain. Proteomics analysis suggested the anti-AD properties of CR might involve inflammation reduction, cell survival enhancement, and mitophagy modulation. CR treatments in both AD mice and Aβ-induced SH-SY5Y cells resulted in reduced pyroptosis, increased LC3 and Beclin1 levels, and activation of the PINK1/Parkin pathway.

Conclusion

The EAC fraction of CR is effective in AD treatment by mitigating pyroptosis, reducing neuroinflammation, and promoting mitophagy, actions facilitated through the PINK1/Parkin pathway.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.