Persicaria hydropiper attenuates oxidative stress and reactive oxygen species, and inhibits amyloid-β/tau in SH-SY5Y cell lines via multiple pathways of Alzheimer's disease

Background Alzheimer's disease (AD) is a neurodegenerative disorder with progression leading to a decline in cognition. Despite the extensive research, conventional therapies have limited activity and often cause side effects. This demands the need for novel, safer, and effective treatment of AD. Objective The objective of this study was to determine the phytochemical constituents and determine the anti-Alzheimer's activity of Persicaria hydropiper. Methods The total phenol and flavonoid content of the Persicaria (MP) methanol extract was determined, and active principles were identified using GC-MS. The neuroprotective activity was investigated using biochemical assays against Aβ 1–42 -induced neurodegeneration in SH-SY5Y neuroblastoma cell lines. Results Phytochemical analysis revealed the presence of phenols (258.33 mg GAE) and flavonoids (48.31 mg QE). GC-MS identified the anti-inflammatory and antioxidant bioactive compounds. MP exhibited strong ABTS and DPPH radical-scavenging activities and inhibited AChE and BACE1 enzymes. In SHSY5Y cells, MP prevented Aβ 1–42 aggregation, restored cell morphology, reduced reactive oxygen species levels, and preserved mitochondrial membrane potential. It suppressed Aβ and tau fibrillation, downregulated Bax and Caspase, upregulated Bcl2, Beclin-1, LC3B-II, and LAMP1, and reduced IL-6, TNF-α, and GSK3β expression, indicating potent neuroprotective, antioxidant, and anti-inflammatory effects. Conclusions Overall, the results imply that Persicaria hydropiper exhibits protective activity on neuroblastoma cell lines by mitigating oxidative stress, Aβ/tau fibrils, cell death, and inflammation while also inducing autophagy induced by Aβ 1–42 . Further in vivo studies are needed to validate the findings to establish the plant as a potential source of anti-Alzheimer's drug.