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<p>Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder affecting approximately 55.2 million individuals globally, with complex pathogenesis involving amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. Current treatments offer only symptomatic relief without halting disease progression. Dl-3-n-butylphthalide (NBP), a small-molecule compound originally derived from celery seeds, has emerged as a promising multi-target therapeutic candidate for AD. Preclinical studies demonstrate that NBP exerts its therapeutic effects in AD by alleviating oxidative stress, enhancing superoxide dismutase (SOD) and glutathione activities, suppressing neuroinflammation by inhibiting NLRP3 inflammasome activation and pro-inflammatory cytokine release (e.g., IL-1β, TNF-α), reducing Aβ deposition and tau hyperphosphorylation, promoting autophagy, and improving synaptic plasticity. A meta-analysis of six trials (<i>n</i> = 851) confirmed that NBP improves Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores with a favorable safety profile, primarily mild gastrointestinal symptoms and transient liver enzyme elevations. This review systematically summarizes recent advances in NBP research, integrating both preclinical mechanisms and clinical evidence, and highlights its potential as a novel multi-target strategy for AD treatment. Further large-scale, long-term trials are warranted to validate its efficacy and explore optimized delivery systems and combination therapies.</p>

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Recent Advances of the Role of Dl-3-n-Butylphthalide in the Treatment of Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年1月3日

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  • Hansi Huang,
  • Jingtao Wu,
  • Zibo Fang,
  • Yuqing Wang,
  • Jingwei Xie,
  • Yiting Guan

摘要

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder affecting approximately 55.2 million individuals globally, with complex pathogenesis involving amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. Current treatments offer only symptomatic relief without halting disease progression. Dl-3-n-butylphthalide (NBP), a small-molecule compound originally derived from celery seeds, has emerged as a promising multi-target therapeutic candidate for AD. Preclinical studies demonstrate that NBP exerts its therapeutic effects in AD by alleviating oxidative stress, enhancing superoxide dismutase (SOD) and glutathione activities, suppressing neuroinflammation by inhibiting NLRP3 inflammasome activation and pro-inflammatory cytokine release (e.g., IL-1β, TNF-α), reducing Aβ deposition and tau hyperphosphorylation, promoting autophagy, and improving synaptic plasticity. A meta-analysis of six trials (n = 851) confirmed that NBP improves Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores with a favorable safety profile, primarily mild gastrointestinal symptoms and transient liver enzyme elevations. This review systematically summarizes recent advances in NBP research, integrating both preclinical mechanisms and clinical evidence, and highlights its potential as a novel multi-target strategy for AD treatment. Further large-scale, long-term trials are warranted to validate its efficacy and explore optimized delivery systems and combination therapies.