Polysaccharide from Schisandra chinensis acts via LRP-1 to reverse microglia activation through suppression of the NF-κB and MAPK signaling

Abstract

Ethnopharmacological relevance: Schisandra chinensis (Turcz.) Baill (S. Chinensis), a traditional Chinese medicine frequently used in the traditional treatment of dementia, its polysaccharide component has been widely reported.

Aim of the study: In this paper, we studied whether SCP2-1, a natural product of homogeneous polysaccharide from S. Chinensis, could improve M1 and M2 polarization and inhibit neuroinflammation through lipoprotein receptor-related protein-1 (LRP-1), and futher exerted anti-inflammatory and neuroprotective effects.

Materials and methods: SCP2-1 was obtained from crude polysaccharide of S. Chinensis, BV2 microglia cells and mice stimulated by LPS were served to detect the positive role of SCP2-1 in M1/M2 polarization. The concentration of cytokine expression, IL-1β, TNF-α, IL-12 and IL-6 for M1 polarization and TGF-β, IL-10, IL-4 and Arg-1 for M2 polarization, in the BV2 and hippocampus were tested by ELISA kits. CD86 and CD206, as surface markers of M1 and M2, were tested by flow cytometry. We examined the expression of LRP-1 in BV2 cells and mouse hippocampus. The addition of siRNA for LRP-1 demonstrated the important role of LRP-1 in the neuroprotection of SCP2-1. Western blot was used to detect the activation of various mitogen-activated protein kinase (MAPKs) pathway, i.e. the phosphorylation of JNK and ERK proteins, and nuclear translocation of nuclear factor κB (NF-κB). H.E. staining was used to observe Histopathological changes.

Results: SCP2-1 could reverse M1/M2 polarization in vitro culture and suppressed M1 polarization in the hippocampus of mice stimulated with LPS. After LPS stimulation, poor levels of LRP-1, hyperactivation of the JNK and NF-κB was appeared, which could improve by SCP2-1. The addition of siRNA for LRP-1 suppressed the protection of SCP2-1 in BV2 microglial cells. More importantly, SCP2-1 could improve LPS-induced cognitive dysfunction in mice in Y-maze and NOR test.

Conclusions: SCP2-1 could improve M1/M2 polarization, especially inhibit M1 polarization, and ameliorate the cognition of mice in Y-maze and NOR test. SCP2-1 play a neuroprotective role through LRP-1 to reverse activation of microglia via suppressing the overactive NF-κB and JNK pathway.

Keywords: Cognition; LRP-1; Microglia; Neuroinflammation; Polarization.