Sayuti_2023_Molecules_28_

Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H(2)O(2)), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as 'kesum', is widely used in traditional medicine. P. minus has been reported to exhibit a few medicinal and pharmacological properties. The current study aimed to investigate the neuroprotective effects of P. minus ethanolic extract (PMEE) on H(2)O(2)-induced neurotoxicity in SH-SY5Y cells. LC-MS/MS revealed the presence of 28 metabolites in PMEE. Our study showed that the PMEE provided neuroprotection against H(2)O(2)-induced oxidative stress by activating the Nrf2/ARE, NF-kappaB/IkappaB and MAPK signaling pathways in PMEE pre-treated differentiated SH-SY5Y cells. Meanwhile, the acetylcholine (ACH) level was increased in the oxidative stress-induced treatment group after 4 h of exposure with H(2)O(2). Molecular docking results with acetylcholinesterase (AChE) depicted that quercitrin showed the highest docking score at -9.5 kcal/mol followed by aloe-emodin, afzelin, and citreorosein at -9.4, -9.3 and -9.0 kcal/mol, respectively, compared to the other PMEE's identified compounds, which show lower docking scores. The results indicate that PMEE has neuroprotective effects on SH-SY5Y neuroblastoma cells in vitro. In conclusion, PMEE may aid in reducing oxidative stress as a preventative therapy for neurodegenerative diseases.