Nano-Honokiol ameliorates the cognitive deficits in TgCRND8 mice of Alzheimer’s disease via inhibiting neuropathology and modulating gut microbiota

• DOI: 10.1016/j.jare.2021.03.012
• Publication Date: 2021-03-31T18:08:48Z
• Authors: Chang Qu; Qiao-Ping Li; Zi-Ren Su; Siu-Po Ip; Qiu-Ju Yuan; You-Liang Xie; Qing-Qing Xu; Wen Yang; Yan-Feng Huang; Yan-Fang Xian; Zhi-Xiu Lin
• Keywords: Honokiol; Neuropathology

Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer's disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy.A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size excellent stability was developed this study to improve solubility HO. The anti-AD Nano-HO determined.Male TgCRND8 mice were daily orally administered or HO at same dosage (20 mg/kg) for 17 consecutive weeks, followed by assessment spatial learning memory functions using Morris Water Maze test (MWMT).Our pharmacokinetic indicated that oral greatly improved Nano-HO. In addition, significantly cognitive deficits inhibited neuroinflammation via suppressing levels TNF-α, IL-6 IL-1β brain, preventing activation microglia (IBA-1) astrocyte (GFAP), reducing β-amyloid (Aβ) deposition cortex hippocampus mice. Moreover, more effective than modulating amyloid precursor protein (APP) processing β-secretase, as well enhancing Aβ-degrading enzymes like neprilysin (NEP). Furthermore, markedly tau hyperphosphorylation decreasing ratio p-Tau (Thr 205)/tau regulating tau-related apoptosis proteins (caspase-3 Bcl-2). attenuated ratios p-JNK/JNK p-35/CDK5, while p-GSK-3β (Ser9)/GSK-3β. Finally, prevented gut microflora dysbiosis a potent manner free HO.Nano-HO improving impairments inhibiting Aβ deposition, through JNK/CDK5/GSK-3β signaling pathway. also potently modulated microbiota community protect These results suggest has good potential further development into agent AD treatment.