Astaxanthin acts via LRP-1 to inhibit inflammation and reverse lipopolysaccharide-induced M1/M2 polarization of microglial cells

Microglia become activated during neuroinflammation and produce neurotoxic and neurotrophic factors, depending on whether they acquire M1 proinflammatory or M2 anti-inflammatory phenotypes. Astaxanthin (ATX), a natural carotenoid, has anti-inflammatory and neuroprotective effects. We investigated whether ATX could reverse M1/M2 polarization and suppress neuroinflammation via low-density lipoprotein receptor-related protein-1 (LRP-1). We observed increased expression of M1 (TNF-α, IL-1β, and CD86) and decreased expression of M2 (Arg-1, IL-10, and CD206) markers in BV2 microglial cells stimulated with lipopolysaccharide (LPS). These alterations were reversed by pretreating the cells with ATX. Activation of the NF-κB and JNK pathways was observed upon LPS stimulation, which was reversed by ATX. ATX-induced M2 polarization was attenuated by inhibition of NF-κB and JNK. Pretreatment of LPS-stimulated BV2 cells with ATX resulted in increased LRP-1 expression. The addition of receptor-associated protein, an LRP-1 antagonist, ameliorated ATX-induced inactivation of NF-κB and JNK signaling, and M2 polarization. ATX promotes M2 polarization to suppress neuroinflammation via LRP-1 by inhibiting NF-κB and JNK signaling. This novel mechanism may suppress neuroinflammation in diseases such as Alzheimer's disease.