| Popis: |
Background Accumulating evidence has indicated that inflammatory damage plays a vital role in the pathogenesis of Alzheimer’s disease (AD) and represents one of the therapeutic targets. Z-Guggulsterone (Z-GS) is an active component extracted from myrrh, which has been widely used as an anti-inflammatory agent. The present study was to investigate the anti-inflammatory and neuroprotective effects of Z-GS on the disease progression, as well as the underlying mechanisms in the transgenic mouse models of AD. Methods Using behavioral, histological, and biochemical methods, outcomes of Z-GS treatment on neuropathology and cognitive deficits were studied in the APPswe/PS1dE9 mice. Results We found that Z-GS treatment resulted in a dramatic improvement of learning and memory deficits, a significant decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a marked alleviation in neuroinflammation, and a profound reduction in synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was strongly suppressed with Z-GS treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice. In addtion, Z-GS modulated anti-inflammatory pathway via decreasing phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65, which was achieved by inhibiting the activation of TLR4. Conclusions Collectively, Our results demonstrate that Z-GS protects neurons against inflammatory damage in AD, and this neuroprotective property involves the TLR4/NF-κB signaling pathway. |
