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Background <p>Alzheimer’s disease (AD) is a neurodegenerative disease that is often accompanied by neuropsychiatric problems, including depression. Lipocalin-2(LCN2), a proinflammatory mediator, exacerbates the symptoms of depression and memory impairment through neuroinflammation. This study investigated the potential of <i>Piper Longum</i> extract(PLE), a traditional Indian medicinal plant, in the treatment of AD and comorbid depression.</p> Methods <p>In this study, we investigated memory impairment and depression-like behaviors through behavioral experiments such as the Y-maze test, Morris water maze test, open field test (OFT), forced swim test (FST), and tail suspension test (TST). We used Western blot, RT-PCR analysis, and immunofluorescence to identify changes in AD-related markers, such as amyloid beta (Aβ) protein, tau phosphorylation, tumor necrosis factor-alpha (TNF-α), and LCN2-related astrocytes, in the brain of Streptozotocin/Chronic Restrain Stress (STZ/Res) mice treated with PLE.</p> Results <p>The PLE group showed significant improvements in the Morris water maze, Y-maze, FST, and TST. Aβ protein, hyperphosphorylation of tau, TNF-α level decreased when treated PLE compared to Donepezil(DPZ). LCN2 merged with GFAP and colocalization was significantly decreased in the PLE-treated group.</p> Conclusion <p>Our findings suggest that <i>Piper longum</i> is a potential natural treatment for AD and depressive comorbidities caused by LCN2-mediated neuroinflammation.</p> Graphical Abstract <p></p>

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Efficacy of Piper Longum Extract in a Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease Combined with Chronic Restraint Through Lipocalin-2-Associated Neuroinflammatory Mechanism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Hyun-Yee Ha,
  • Seung-Hyeon Han,
  • Seung-Hun Cho

摘要

Background

Alzheimer’s disease (AD) is a neurodegenerative disease that is often accompanied by neuropsychiatric problems, including depression. Lipocalin-2(LCN2), a proinflammatory mediator, exacerbates the symptoms of depression and memory impairment through neuroinflammation. This study investigated the potential of Piper Longum extract(PLE), a traditional Indian medicinal plant, in the treatment of AD and comorbid depression.

Methods

In this study, we investigated memory impairment and depression-like behaviors through behavioral experiments such as the Y-maze test, Morris water maze test, open field test (OFT), forced swim test (FST), and tail suspension test (TST). We used Western blot, RT-PCR analysis, and immunofluorescence to identify changes in AD-related markers, such as amyloid beta (Aβ) protein, tau phosphorylation, tumor necrosis factor-alpha (TNF-α), and LCN2-related astrocytes, in the brain of Streptozotocin/Chronic Restrain Stress (STZ/Res) mice treated with PLE.

Results

The PLE group showed significant improvements in the Morris water maze, Y-maze, FST, and TST. Aβ protein, hyperphosphorylation of tau, TNF-α level decreased when treated PLE compared to Donepezil(DPZ). LCN2 merged with GFAP and colocalization was significantly decreased in the PLE-treated group.

Conclusion

Our findings suggest that Piper longum is a potential natural treatment for AD and depressive comorbidities caused by LCN2-mediated neuroinflammation.

Graphical Abstract