Structural analysis and anti-neuroinflammatory activity of the water-soluble heteropolysaccharide PTTBP-2-2 from...

Neuroinflammation is closely linked to Alzheimer's disease, where the deposition of amyloid-beta activates microglia, triggering multiple processes that lead to neuronal damage and cognitive decline. However, studies have shown that water extract of Pinellia ternata can improve cognitive function and reduce inflammatory response in the brain injury of mice. Herein, a water-soluble polysaccharide, PTTBP-2-2, with a molecular weight of 11.7 kDa, consisting of D-Glc, D-Gal, D-Xyl, and L-Ara was isolated from P. ternata. Methylation analysis, partial acid hydrolysis, and nuclear magnetic resonance revealed that the of PTTBP-2-2 backbone consisted of →4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, and →6)-α-D-Galp-(1→ residues, with side chains substituted at O-2, O-3, and O-6 positions of →4)-α-D-Glcp-(1→. In vitro experiments demonstrated that PTTBP-2-2 significantly reduced nitric oxide levels in BV2 microglia cells and suppressed the expression of pro-inflammatory genes, including COX2, iNOS, TNF-α, IL-1β, and IL-6. These factors are key mediators of neuroinflammation. Mechanistic investigations revealed that the anti-neuroinflammatory activity of PTTBP-2-2 was mediated through the regulation of NF-κB and Nrf2/HO-1 signaling pathways. Overall, PTTBP-2-2 shows potential as a therapeutic agent for the treatment of neuroinflammation.