An Efficient Starch-Based Delivery System Ameliorates Naringin’s Uptake to Mitigate Acrylamide-Induced Oxidative Stress in Mice

Naringin (NAR), a potent antioxidant flavonoid, suffers from low oral bioavailability, limiting its therapeutic application. Here, an efficient octenyl succinic anhydride-modified porous starch (OSAPS) carrier was adopted to enhance NAR’s delivery and efficacy against acrylamide (AA)-induced oxidative stress. In Caco-2 cells, the OSAPS-NAR complex demonstrated superior cellular uptake and more effectively mitigated AA-induced cytotoxicity compared to free NAR. Causally, this protection was attributed to its enhanced antioxidant capacity to suppress reactive oxygen species generation, maintain mitochondrial membrane potential, and prevent glutathione (GSH) depletion. Critically, these in vitro advantages translated to remarkable in vivo outcomes. The OSAPS-NAR complex led to a striking 7.91-fold increase in peak plasma concentration and an 11.05-fold increase in relative bioavailability in mice. This enhanced pharmacokinetic profile directly translated to superior antioxidant activities in serum and liver tissues by elevating total antioxidant capacity and GSH content, while simultaneously reducing malondialdehyde levels. These effects collectively led to marked amelioration of AA-induced hepatotoxicity, normalization of the liver index, and restoration of hepatic cellular architecture. In conclusion, the complex effectively overcame NAR’s pharmacokinetic limitations, thereby potentiating its ability to modulate cellular redox imbalance and protect against oxidative organ injury. This work provided a robust proof-of-concept for OSAPS-NAR as a promising nutraceutical agent for combating pathologies driven by oxidative stress.