数字农科院2.0

Nuciferine alleviates cognitive impairment by modulating endoplasmic reticulum stress in D-galactose-induced aging mice

文献类型： 外文期刊

作者： Xiaojie Yang;Juntao Zhang;Weimin Wang;Xinyan Wu;Yuxuan Liu;Jianjun Deng;Haixia Yang

作者机构：

关键词： Aging;Cognitive impairment;Endoplasmic reticulum stress;Neuroprotection;Nuciferine

期刊名称： Food Bioscience

ISSN： 2212-4292

年卷期： 2025 年 71 卷

页码：

收录情况： SCIE（2025版） ; ; 农林核心（2024版）

摘要： Aging is a ubiquitous process leading to functional decline, with the cognitive impairment as a general and critical geriatric challenge. Healthy diet effectively extends life span and health span. However, anti-aging potential of bioactive phytochemicals requires further investigation. Nuciferine (NF), an aporphine alkaloid extracted from lotus, has pharmacological effects including anti-obesity and anti-inflammation, but the impact of NF on aging-induced cognitive impairment hasn't been largely known. This study demonstrated that dietary NF (5 and 10 mg/kg) improved the appearance, locomotor, learning, and spatial memory ability of D-galactose (D-gal)-induced aging mice assessed by behavioral tests. Histopathological analysis showed NF ameliorated aging-induced cerebral injuries. Additionally, NF (5 and 10 mg/kg) improved neurogenesis and synaptogenesis via increasing the genes expression of Neun by 33.1% and 44.3%, Dcx by 44.1% and 50.2%, Bdnf by 55.7% and 61.8%, as well as Psd95 by 13.4% and 25.9%, respectively. NF also inhibited neuronal apoptosis and neuroinflammation genes expression. Molecular docking revealed NF spontaneously interacted with the endoplasmic reticulum (ER) transmembrane receptors, with PERK-NF complex as the most favorable interaction of −9.4279 kcal/mol calculated docking energy. Ten mg/kg NF was further demonstrated to downregulate ER stress protein expression, including p-PERK/PERK by 69.2%, GRP78 by 61.2%, and CHOP by 63.4% in vivo, corresponding with the gene expression inhibition. Suppressing ER stress in D-gal-treated SH-SY5Y cells abolished the neuroprotective effects of NF, confirming that NF mitigated neuronal dysfunction through the novel mechanism ER stress. Our findings suggest that NF is a potential phytochemical to improve aging-induced cognitive impairment, providing strategies for functional food exploration.

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