Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing
1Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, 45 Changchun Street, Beijing, China.
Background:
Alzheimer's disease (AD), has caused a mass of disability and mortality in elder populations, which increases global health burden. There are still limited effective disease-modifying drugs. Alleviating microglia-evoked neuroinflammation has become a promising treatment strategy for AD. Ginsenoside Compound K has been demonstrated to exhibit anti-inflammatory and neuroprotective benefits. Here we measured the effects of Ginsenoside Compound K in inhibiting amyloid-induced microglia inflammation and the possible molecular mechanisms and target of action in vitro.
Methods:
The cytotoxicity of all chemical reagents on BV2 cells were evaluated using the MTT assay. qRT-PCR and ELISA were carried out to detect the inflammatory cytokines levels. Western blot was utilized to determine the effect of Ginsenoside Compound K on the nuclear factor-κB (NF-κB) p65 nuclear translocation. Antagonist Receptor Associated Protein (RAP) was used to verify the engagement of low-density lipoprotein receptor-related protein 1(LRP1).
Results:
Ginsenoside Compound K diminished inflammatory cytokine production and reversed NF-κB p65 nuclear translocation induced by Aβ42 oligomers. LRP1 expression was up-regulated by Ginsenoside Compound K. When LRP1 was blocked by antagonist RAP, the protective effect of Ginsenoside Compound K was massively eliminated.
Conclusion:
These observations provide evidence for anti-inflammatory effect of Ginsenoside Compound K through NF-κB pathway via LRP1 activation, and support further evaluation of Ginsenoside Compound K as a potential effective modulator for AD.
Insights
Ginsenoside Compound K reduces inflammation in Alzheimer's disease models by targeting the NF-κB pathway via LRP1 activation. This compound shows promise for treating neuroinflammation associated with Alzheimer's disease.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Alzheimer's disease (AD) poses a significant global health burden with limited disease-modifying treatments.
- Neuroinflammation, particularly microglia-evoked inflammation, is a key target for AD therapeutic strategies.
- Ginsenoside Compound K exhibits known anti-inflammatory and neuroprotective properties.
Purpose of the Study:
- To investigate the efficacy of Ginsenoside Compound K in inhibiting amyloid-beta-induced microglia inflammation in vitro.
- To elucidate the molecular mechanisms and identify the target of action for Ginsenoside Compound K's anti-inflammatory effects in AD.
Main Methods:
- Cytotoxicity was assessed using MTT assays on BV2 cells.
- Quantitative real-time PCR (qRT-PCR) and ELISA measured inflammatory cytokine levels.
- Western blot analyzed nuclear factor-kappa B (NF-κB) p65 nuclear translocation, with LRP1 engagement verified using antagonist Receptor Associated Protein (RAP).
Main Results:
- Ginsenoside Compound K significantly reduced inflammatory cytokine production and reversed amyloid-beta oligomer-induced NF-κB p65 nuclear translocation.
- The compound upregulated low-density lipoprotein receptor-related protein 1 (LRP1) expression.
- Blocking LRP1 with RAP diminished the protective effects of Ginsenoside Compound K.
Conclusions:
- Ginsenoside Compound K demonstrates anti-inflammatory effects in microglia via the NF-κB pathway, mediated by LRP1 activation.
- These findings support the potential of Ginsenoside Compound K as a therapeutic agent for Alzheimer's disease by modulating neuroinflammation.
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