| First Author | Nam Y | Year | 2024 |
| Journal | Biomed Pharmacother | Volume | 177 |
| Pages | 117090 | PubMed ID | 38968796 |
| Mgi Jnum | J:353055 | Mgi Id | MGI:7708755 |
| Doi | 10.1016/j.biopha.2024.117090 | Citation | Nam Y, et al. (2024) Platycodon grandiflorum root extract inhibits Abeta deposition by breaking the vicious circle linking oxidative stress and neuroinflammation in Alzheimer's disease. Biomed Pharmacother 177:117090 |
| abstractText | Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Abeta deposition. Thus, we aim to identify the mechanism through which PGE inhibits Abeta deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H(2)O(2)- and Abeta-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Abeta deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Abeta-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Abeta-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Abeta, and inhibits neuroinflammation and Abeta deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes. |
