Oral Icariin Nanoparticles Ameliorate Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress

Chronic inflammatory liver conditions, such as nonalcoholic fatty liver disease (NAFLD), are frequently exacerbated by oxidative stress, rendering the neutralization of reactive oxygen species (ROS) crucial for their amelioration. Oral administration of nanoparticles (NPs) presents an optimal strategy for NAFLD management due to its convenience. This research aimed to overcome the poor water solubility and low bioavailability of icariin (ICA) by engineering an oral nanosystem, ICA-loaded poly(lactic-<i>co</i>-glycolic acid)-poly(ethylene glycol) (PLGA) NPs with chitosan (CS) and mannose surface modification (ICA-NPs), to augment ICA's antioxidant potency against NAFLD. Methods involved comprehensive in vitro characterization of ICA-NPs (including dispersibility, biocompatibility, HepG2 targeting, and ROS scavenging capabilities) and in vivo studies in high-fat diet (HFD)-induced NAFLD mice, assessing liver accumulation, ROS scavenging, and antiobesity effects across multiple experimental groups. Results demonstrated that this targeted oral NP system significantly amplified ICA's therapeutic impact, leading to substantial reductions in body weight, diminished white adipose tissue accumulation, decreased hepatic lipid content, improved hepatic function, and a notable suppression of ROS in the livers of NAFLD-afflicted mice. In conclusion, by harnessing the precision of targeted delivery, this oral nanosystem not only enhances ICA's therapeutic efficacy but also establishes a safe and effective platform for the oral administration of herbal remedies for liver conditions, suggesting a promising avenue for advancing herbal medicine in liver disease treatment.