Discovery of Taxus chinensis fruit wine as potentially functional food against Alzheimer's disease by UHPLC-QE-MS/MS, network pharmacology and molecular docking.

Abstract

Nowadays, there is no specific cure for Alzheimer's disease (AD), but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. However, the chemical constituents and molecular mechanisms of TCFW still remain unknown. In this study, chemical profiling with UHPLC-QE-MS/MS, network pharmacology and molecular docking were integrated to fastly explore the potential chemicals and mechanisms of TCFW against AD. A total of 31 chemical components in TCFW were detected and identified compared with the solvent wine of TCFW by UHPLC-QE-MS/MS. Then, 27 potential key targets and 14 chemical compounds of TCFW were uncovered for the improvement of AD by network pharmacology and molecular docking. These 14 compounds were reported to have diverse bioactivities such as neuroprotective activity, antifibrotic activity, anticancer activity, antiviral activity and effectiveness in the treatment of neuronal injury, Alzheimer's disease, etc. Among these 27 targets affected by TCFW predicted by our approach, AKT1, PTGS2, NOS3, NOS2, INS, ESR1, ESR2, BDNF, IL6, IL1B, DRD2 and ACHE were significantly altered in AD. The GO and KEGG enrichment analyses revealed that TCFW mainly acted on oxidative response, inflammatory response, insulin secretion, amyloid fibril formation, neurodegenerative pathway-multiple diseases, Alzheimer's disease, longevity regulation pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc, which were the main pathogenesis of AD. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by cognitive and behavioral dysfunction. Nowadays, there is no specific cure for AD, but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. This study proposed a fastly integrated method to explore the potential chemicals and mechanisms of TCFW against AD by UHPLC-QE-MS/MS, network pharmacology and molecular docking. Here, we found that TCFW may ameliorate AD by reversing many biological events, including oxidative stress, inflammatory response, neuronal apoptosis, insulin secretion, amyloid fibril formation, and T cell co-stimulation, which may provide some insights for the development and research of anti-AD drugs.