An arabinoxylan (AOP70-1) isolated from Alpinia oxyphylla alleviates neuroinflammation and neurotoxicity by TLR4/MyD88/NF-κB pathway

Alpinia oxyphylla is famous for its neuroprotective and memory-improving effects. A crude polysaccharide AO70 from A. oxyphylla remarkably ameliorated neuroinflammation and cognitive dysfunction in Alzheimer's disease mice. This study aimed to explore the bioactive component of AO70 and its mechanism of action. A homogeneous polysaccharide (AOP70-1) rich in arabinose and xylose was purified from AO70, which was consisted of alpha-L-Araf-(1 ->, f-(1 ->, -> 5)-alpha-L-Ara f-(1 ->, (1-D-Xylp-(1 ->,-> 2,4)-(1-D-Xylp-(1 ->, p-(1 ->,-> 2,4)-(1-D-Xyl p-(1 ->, -> 2,3,4)-(1-D-Xyl p-(1 ->, alpha-L-Rhap-(1 ->, p-(1 ->, alpha-DManp-(1 ->, p-(1 ->, -> 4)-alpha-D-Glc p-(1 ->, -> 4)-alpha-D-Glc p A-(1 ->, (1-D-Galp-(1 ->, p-(1 ->, -> 2)-alpha-D-Gal p-(1 ->, -> 6)-alpha-D-Gal p-(1 -> and -> 3,6)-alpha-D-Man p-(1 ->. AOP70-1 (2.5, 5, 10 mu M) significantly suppressed NO, IL-1(1, and TNF-alpha production in a concentration-dependent manner and inhibited the migration of BV2 microglia. AOP70-1 inhibited LPSmediated activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), and nuclear factor kappa B (NF-kappa B). Moreover, AOP70-1 exerted neuroprotection on SH-SY5Y cells and primary neurons by reducing neuronal apoptosis (72 %, 44 %), alleviating ROS accumulation (63 %, 55 %), and improving mitochondrial membrane potential (63 %, 77 %). Overall, AOP70-1 is one of the major bioactive components in AO70 from A. oxyphylla, , which has great potential in the prevention and treatment of neuroinflammation.