| First Author | Yu L | Year | 2024 |
| Journal | Phytother Res | Volume | 38 |
| Issue | 9 | Pages | 4815-4831 |
| PubMed ID | 39225174 | Mgi Jnum | J:360719 |
| Mgi Id | MGI:7787213 | Doi | 10.1002/ptr.8060 |
| Citation | Yu L, et al. (2024) Thonningianin A from Penthorum chinense Pursh as a targeted inhibitor of Alzheimer's disease-related beta-amyloid and Tau proteins. Phytother Res 38(9):4815-4831 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disorder characterized by complex pathogenesis mechanisms. Among these, beta-amyloid plaques and hyperphosphorylated Tau protein tangles have been identified as significant contributors to neuronal damage. This study investigates thonningianin A (TA) from Penthorum chinense Pursh (PCP) as a potential inhibitor targeting these pivotal proteins in AD progression. The inhibitory potential of PCP and TA on Abeta fibrillization was initially investigated. Subsequently, ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and biolayer interferometry were employed to determine TA's affinity for both Abeta and Tau. The inhibitory effects of TA on the levels and cytotoxicity of AD-related proteins were then assessed. In 3xTg-AD mice, the therapeutic potential of TA was evaluated. Additionally, the molecular interactions between TA and either Abeta or Tau were explored using molecular docking. We found that PCP-total ethanol extract and TA significantly inhibited Abeta fibrillization. Additionally, TA demonstrated strong affinity to Abeta and Tau, reduced levels of amyloid precursor protein and Tau, and alleviated mitochondrial distress in PC-12 cells. In 3xTg-AD mice, TA improved cognition, reduced Abeta and Tau pathology, and strengthened neurons. Moreover, molecular analyses revealed efficient binding of TA to Abeta and Tau. In conclusion, TA, derived from PCP, shows significant neuroprotection against AD proteins, highlighting its potential as an anti-AD drug candidate. |
