Elucidation of Pharmacological Mechanism Underlying the Anti-Alzheimer's Disease Effects of Evodia rutaecarpa and Discovery of Novel Lead Molecules: An In Silico Study.
Lulu Zhang, Jia Xu, Jiejie Guo, Yun Wang, Qinwen Wang
Molecules August 3, 2023 DOI: 10.3390/molecules28155846 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In silico study with behavioral experiment Peer reviewed |
|---|---|
| Population | AD model mice |
| Intervention | E. rutaecarpa extract |
| Keywords | Alzheimer’s disease Evodia rutaecarpa Hormones Migraines Neurotransmitter inflammation Pharmacology network Dementia Herbal medicine #alzheimersresearch alzheimer's disease Neurodegeneration #traditionalmedicine chinese medicine Natural remedies |
| Citations | 9 |
| Key findings | Evodia rutaecarpa compounds target Alzheimer's disease through multiple pathways, with alkaloids binding strongly to key proteins involved in serotonergic signaling, hormones, anti-neuroinflammation, transcription regulation, and molecular chaperones. |
Abstract
Alzheimer's disease (AD) is a brain disease with a peculiarity of multiformity and an insidious onset. Multiple-target drugs, especially Chinese traditional medicine, have achieved a measure of success in AD treatment. Evodia rutaecarpa (Juss.) Benth. (Wuzhuyu, WZY, i.e., E. rutaecarpa), a traditional Chinese herb, has been identified as an effective drug to cure migraines. To our surprise, our in silico study showed that rather than migraines, Alzheimer's disease was the primary disease to which the E. rutaecarpa active compounds were targeted. Correspondingly, a behavioral experiment showed that E. rutaecarpa extract could improve impairments in learning and memory in AD model mice. However, the mechanism underlying the way that E. rutaecarpa compounds target AD is still not clear. For this purpose, we employed methods of pharmacology networking and molecular docking to explore this mechanism. We found that E. rutaecarpa showed significant AD-targeting characteristics, and alkaloids of E. rutaecarpa played the main role in binding to the key nodes of AD. Our research detected that E. rutaecarpa affects the pathologic development of AD through the serotonergic synapse signaling pathway (SLC6A4), hormones (PTGS2, ESR1, AR), anti-neuroinflammation (SRC, TNF, NOS3), transcription regulation (NR3C1), and molecular chaperones (HSP90AA1), especially in the key nodes of PTGS2, AR, SLCA64, and SRC. Graveoline, 5-methoxy-N, N-dimethyltryptamine, dehydroevodiamine, and goshuyuamide II in E. rutaecarpa show stronger binding affinities to these key proteins than currently known preclinical and clinical drugs, showing a great potential to be developed as lead molecules for treating AD.