Andrographolide exerts a neuroprotective effect by regulating the LRP1-mediated PPARγ/NF-κB pathway

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Low-density lipoprotein receptor-associated protein 1 (LRP1) is crucial in brain function, and its reduced expression exacerbates Alzheimer's disease (AD) pathology.
• Andrographolide (Andro) exhibits neuroprotective effects, but its mechanism in AD, particularly concerning neuroinflammation, is not fully understood.

Purpose of the Study:

• To investigate if Andrographolide (Andro) can mitigate neuroinflammation in Alzheimer's disease (AD) by targeting the LRP1-mediated Peroxisome proliferator-activated receptor gamma (PPARγ)/Nuclear factor-kappa B (NF-κB) pathway.

Main Methods:

• Utilized Aβ-induced BV-2 cell models to assess Andro's effects on cell viability, LRP1 expression, and inflammatory markers.
• Investigated the role of LRP1 and PPARγ by employing knockdown techniques in conjunction with Andro and Aβ treatment.
• Measured key indicators including p-NF-κB (p65) and NF-κB(p65) expression, NF-κB DNA binding activity, and levels of IL-1β, IL-6, and TNF-α.

Main Results:

• Andrographolide (Andro) treatment increased BV-2 cell viability and LRP1 expression while decreasing p-NF-κB (p65), NF-κB(p65), IL-1β, IL-6, and TNF-α levels in Aβ-induced cells.
• Knockdown of LRP1 or PPARγ reversed the anti-inflammatory effects of Andro, leading to increased p-NF-κB (p65), NF-κB(p65), and inflammatory cytokine expression.
• These results indicate Andro's efficacy in attenuating Aβ-induced cytotoxicity through the LRP1-mediated PPARγ/NF-κB pathway.

Conclusions:

• Andrographolide (Andro) demonstrates potential in reducing Alzheimer's disease (AD)-associated neuroinflammation.
• The study highlights the LRP1-mediated PPARγ/NF-κB pathway as a key mechanism through which Andro exerts its neuroprotective effects against Aβ-induced neuroinflammation.