According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 → 6)-β-D-galp-(1 → [6)-β-D-manp-(1] → 4)-α-D-Glcp-(1 → 6)-α-D-glcp-(1 → 2)-β-D-galp-(1 → [4)-α-D-glcp-(1 → 6)-β-D-manp-(1 → 2)-β-D-galp-(1] → 6)-β-D-glcp-(1 → 6)-β-D-glcp-(1→ with two side chains attached to O-4 of →6)-β-D-galp-(1→ and O-3 of →6)-β-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD. 3 2
