Hepatoprotective Effects of Quercetin‐Chitosan Nanoparticles on Nonalcoholic Fatty Liver Disease: In Vivo Study

Metabolic dysfunction associated steatotic liver disease (MASLD) is a common chronic liver disorder characterized by hepatic steatosis, inflammation, and progression to fibrosis and cirrhosis. Despite advances in pharmacotherapy, including thyroid hormone receptor β agonists (resmetirom) and GLP 1 receptor agonists, no universally accepted curative treatment exists. Nutraceuticals such as quercetin offer promising hepatoprotective effects, yet their clinical translation is limited by low bioavailability and stability. In this study, we evaluated the therapeutic potential of chitosan-encapsulated quercetin (Que-CH) nanoparticles in a high-fat diet rat model of MASLD. Que-CH nanoparticles were characterized by particle size (~190 nm), positive zeta potential (+56.5 mV), and 65% encapsulation efficiency. Treatment with Que-CH significantly reduced serum IL-1β, improved liver histology by decreasing macro- and microvesicular steatosis, and lowered the Bax/Bcl-2 ratio, indicating reduced hepatocyte apoptosis. These results suggest that Que-CH nanoparticles enhance the bioactivity of quercetin, exerting anti-inflammatory, anti-apoptotic, and lipid-lowering effects in MASLD. This study highlights the potential of nanocarrier-based nutraceutical interventions as complementary strategies for liver steatosis management, while further mechanistic studies and pharmacokinetic evaluations are warranted to support clinical translation.