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

IF 8.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2025-04-01 Epub 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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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. Aβ1–42-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 Aβ1–42-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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姜黄文玉金提取物通过PINK1/Parkin介导的自噬减轻阿尔茨海默病的认知缺陷,抑制焦亡
背景:焦亡和线粒体自噬在阿尔茨海默病(AD)的治疗中引起了极大的关注。姜黄(Curcumae Radix, CR)是一种被广泛用于治疗神经系统疾病的中药。然而,其在AD中的影响和机制作用尚不清楚。目的探讨CR活性部位在AD治疗中的作用及其潜在机制。方法采用UHPLC-Triple-TOF/MS对scr提取物进行定性分析。a β1 - 42诱导小鼠每天灌胃给药3周。通过Y迷宫、新物体识别和八臂迷宫测试评估AD模型小鼠的认知能力。用定量蛋白质组学方法鉴定了CR提取物的治疗靶点。在体内和体外环境下,通过Western blot (WB)、免疫荧光(IF)染色和ELISA检测对焦亡和有丝分裂的影响。结果川芎提取物乙酸乙酯(EAC)部位抗ad效果最佳。CR提取物增强了Aβ1 - 42诱导小鼠的记忆和认知能力,改善了神经元形态,减少了Aβ在大脑中的积累。蛋白质组学分析表明,CR的抗ad特性可能涉及炎症减少、细胞存活增强和线粒体自噬调节。在AD小鼠和a β诱导的SH-SY5Y细胞中,CR处理导致焦亡减少,LC3和Beclin1水平升高,PINK1/Parkin通路激活。结论CR的EAC部分可通过PINK1/Parkin通路减轻焦亡,减轻神经炎症,促进有丝分裂,从而有效治疗AD。
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来源期刊
Phytomedicine
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.
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