Protective effect of wild polysaccharides extracted from Ulva prolifera on oxidative stress damage in valproic acid-induced neuronal cells

Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, with prenatal exposure to valproic acid (VPA) being a recognized environmental risk factor for ASD, closely associated with its neurotoxic mechanism and oxidative stress. Marine green algae, such as Ulva prolifera , are rich sources of bioactive polysaccharides known for their antioxidant, anti-inflammatory, lipid-lowering, anti-tumor, and neuroprotective properties, with a core focus on antioxidant effects. Therefore, this study aims to investigate the protective effects and potential mechanisms of Ulva prolifera polysaccharides (PUPs) on oxidative stress damage induced by VPA in mouse hippocampal neuronal HT22 cells. Method The primary structure of PUPs was determined through infrared spectroscopy, liquid chromatography, and gel permeation chromatography. PUPs intervention in the VPA-induced HT22 oxidative damage cell model was used to measure oxidative stress factor levels. Results PUPs were characterized as composite polysaccharides with α-glycosidic bonds, sulfate ions, and aldonic acids, containing mannose, rhamnose, glucuronic acid, glucose, galactose, and xylose. The main molecular weight (Mw) was 2.124 kDa (80.535%). In vitro experiments revealed that PUPs significantly increased cell viability in the VPA model, enhanced intracellular SOD and CAT activities to boost antioxidant capacity, and concurrently reduced ROS levels and MDA content. Western blot analysis revealed that PUPs increased Nrf2, HO-1, and IκBα levels, while decreasing the expression levels of Keap1, p-NF-κB-p65/NF-κB-65, p-Erk/Erk, p-p38/p38, and p-JNK/JNK. Conclusions PUPs demonstrate a significant protective effect against VPA-induced oxidative stress damage in HT22 neuronal cells. As a natural antioxidant, PUPs hold promising potential for the prevention and adjunct treatment of ASD-related neuronal oxidative stress damage.