A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.

Background/Objectives: Gamma-oryzanol (ORZ), a bioactive compound extracted from rice bran oil, has health-promoting properties but limited therapeutic use due to poor stability and bioavailability. This study aimed to synthesize gamma-oryzanol-encapsulated nanoparticles (ORZ-NPs) and investigate their anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages. Methods: ORZ-NPs were synthesized via nanoprecipitation and characterized by dynamic light scattering and transmission electron microscopy. ORZ content was assessed using high performance liquid chromatography. In vitro release was determined using a dialysis method. Inducible nitric oxide synthase (iNOS) was assessed by Western blotting, nitric oxide (NO) by Griess assay, and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Results: ORZ-NPs exhibited spherical morphology with a mean particle size of 93.320 ± 2.027 nm, polydispersity index 0.149 ± 0.025, and zeta potential −22.400 ± 0.252 mV. ORZ remained stable for 90 days. In vitro release reached 70% at 24 h in PBS (pH 7.4). At 50 μg mL⁻¹, ORZ-NPs significantly decreased iNOS and NO production (approximately 65% of control, p < 0.01), without affecting TNF-α or IL-6. Conclusions: ORZ-NPs demonstrate selective anti-inflammatory activities by suppressing iNOS and NO production while pro-inflammatory cytokines remain unaffected. These findings suggest a partial modulatory effect on the inflammatory signaling pathway.