| First Author | Liu J | Year | 2022 |
| Journal | Biochem Pharmacol | Volume | 202 |
| Pages | 115149 | PubMed ID | 35714682 |
| Mgi Jnum | J:326136 | Mgi Id | MGI:7293917 |
| Doi | 10.1016/j.bcp.2022.115149 | Citation | Liu J, et al. (2022) Z-Guggulsterone attenuates cognitive defects and decreases neuroinflammation in APPswe/PS1dE9 mice through inhibiting the TLR4 signaling pathway. Biochem Pharmacol 202:115149 |
| abstractText | Growing evidence indicates that inflammatory damage is implicated in the pathogenesis of Alzheimer's disease (AD). Z-Guggulsterone (Z-GS) is a natural steroid, which is extracted from Commiphora mukul and has anti-inflammatory effects in vivo and in vitro. In the present study, we investigated the disease-modifying effects of chronic Z-GS administration on the cognitive and neuropathological impairments in the transgenic mouse models of AD. We found that chronic Z-GS administration prevented learning and memory deficits in the APPswe/PS1dE9 mice. In addition, Z-GS treatment significantly decreased cerebral amyloid-beta (Abeta) levels and plaque burden via inhibiting amyloid precursor protein (APP) processing by reducing beta-site APP cleaving enzyme 1 (BACE1) expression in the APPswe/PS1dE9 mice. We also found that Z-GS treatment markedly alleviated neuroinflammation and reduced synaptic defects in the APPswe/PS1dE9 mice. Furthermore, the activated TLR4/NF-kappaB signaling pathways in APPswe/PS1dE9 mice were remarkably inhibited by Z-GS treatment, which was achieved via suppressing the phosphorylation of JNK. Collectively, our data demonstrate that chronic Z-GS treatment restores cognitive defects and reverses multiple neuropathological impairments in the APPswe/PS1dE9 mice. This study provides novel insights into the neuroprotective effects and neurobiological mechanisms of Z-GS on AD, indicating that Z-GS is a promising disease-modifying agent for the treatment of AD. |
