A heteropolysaccharide from Hypsizygus ulmarius fruit bodies attenuates D-galactose-induced cognitive decline by enhancing mitochondrial function and improving antioxidant activity in mice

The study aimed to examine the antioxidant properties in vitro and the in vivo D-galactose-induced oxidative damage model from the fruiting bodies of Hypsizygus ulmarius Polysaccharide (HUP), which have an average molecular weight of 2.076 × 10³ Da and are primarily composed of glucose and galactose, with minor sugars including xylose, rhamnose, fucose, and mannose. Through in vitro antioxidant tests, HUP exhibited iron-reducing ability, β-carotene bleaching inhibition, and hydroxyl radical scavenging action. Additionally, in vivo antioxidant assays demonstrated that HUP at 200 or 400 mg/kg BW and α-tocopherol as positive control could significantly increase the activities of enzymic antioxidants (CAT, SOD, GSH-Px, GST, and GR), non-enzymic antioxidants (TAOC, GSH, Vit C), in the serum and brain of D-Gal aging-induced mice. The levels of LPO, HPO, PCO, and AOPP levels were decreased on treatment with HUP and boosted the brain, spleen, and thymus indices, improved learning and memory, and stimulated the immune system in older mice. Treatment with HUP also reduced an increase in acetylcholinesterase activity. The decreased activities of NADH dehydrogenase, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH) in the brain mitochondria were restored to normal levels. In all biochemical parameters, the HUP had a dose-dependent positive effect, with 400 mg/kg being the most beneficial According to the current findings, HUP may offer a new source of natural antioxidants for use in functional foods and nutritional supplements.