Lycium barbarum glycopeptide alleviates retinal inflammation by suppressing microglial M1 polarization via NF-κB/MAPK pathways

Abstract

Lycium barbarum glycopeptide (LBGP) is a known glycoconjugate with various pharmacological benefits, notably anti-inflammatory properties, though its impact on retinal inflammatory conditions is not fully understood. This research evaluated the impact of LBGP on retinal inflammation using a diabetic retinopathy (DR) mouse model induced by streptozotocin (STZ), along with LPS/IFN-γ (L/I)-stimulated BV2 microglia and primary retinal microglia. In vivo, administration of LBGP effectively enhances retinal thickness, structure, and function in diabetic mice. Additionally, it prevents microglial activation and inflammation. In vitro, LBGP pretreatment significantly reversed L/I-induced morphological alterations in microglial area, perimeter, Feret's diameter, and roundness. LBGP significantly alleviated L/I-induced microglial activation in primary and BV2 microglia. LBGP shifted M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype by downregulating M1 markers (IL-6, IL-1β, iNOS, COX2, CD86, and CD16) and upregulating M2 markers (CD206 and arginase 1). Additionally, LBGP reduced the upregulation of NF-κB and MAPK pathways in L/I-stimulated BV2 microglial cells. Our study suggests that LBGP protects against microglial overactivation and diminishes the secretion of inflammatory molecules from microglia in vivo and vitro, potentially through attenuation of the NF-κB and MAPK signaling pathways.

Keywords: DR; LBGP; MAPK; Microglia; NF-κB; Polarization; Retinal inflammatory diseases.