Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing NF-κB.

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.