Preparation and Multitarget Anti‐AD Activity Study of Chondroitin Sulfate Lithium in AD Mice Induced by Combination of D‐Gal/AlCl<sub>3</sub>
Debo Gao, Pingli Li, Fei Gao, Yangjun Feng, Xiaolin Li, Delong Li, Yuqin Li, Yuliang Xiao
Abstract
Previous studies have demonstrated that both CS and LiCl possess anti‐Alzheimer’s disease (AD) activities. We prepared chondroitin sulfate‐Li (CS‐Li) and investigated its effect on AD and explored the possible mechanisms both in vitro and in vivo . We found that CS‐Li could inhibit amyloid β (A β ) aggregation and protect SH‐SY5Y cells from A β 1-42 ‐induced cytotoxicity in vitro . In D‐gal and AlCl 3 ‐induced AD mouse model, CS‐Li improves the spatial learning and memory abilities of AD mice, reverses the nuclear pyknosis and cell edema, and increases the survival rate of neurons in hippocampus of mice. Moreover, CS‐Li significantly increased the levels of GSH‐Px, Na + /K + ‐ATPase, and ChAT and decreased the levels of MDA and AchE in AD mice. Western blot results demonstrated that CS‐Li could decrease the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of p‐GSK‐3 β (Ser9) and PP2A and inhibit the expression of proinflammatory factors through inhibiting NF‐ κ B nuclear translocation by activating the MAPK signaling pathways. In a word, CS‐Li can delay AD development through multitarget processes, including A β aggregation inhibition, oxidative stress damage, tau hyperphosphorylation, and inflammatory response, thereby improves learning and memory abilities.