Red rice bran extract (RRBE) is rich in phytonutrients and has been shown to have anti-diabetic, anti-inflammatory, and antioxidant properties. However, its anti-hepatic steatosis and anti-dyslipidemic properties have not been thoroughly investigated. This study examined the aforementioned properties of RRBE, the underlying mechanism by which it alleviated non-alcoholic fatty liver disease in high-fat diet (HFD)-fed mice, and its major bioactive constituents. The mice were divided into four groups based on their diet: (1) low-fat diet (LFD), (2) LFD with high-dose RRBE (1 g/kg/day), (3) HFD, and (4) HFD with three different doses of RRBE (0.25, 0.5, and 1 g/kg/day). The administration of RRBE, especially at medium and high doses, significantly mitigated HFD-induced hepatosteatosis and concomitantly improved the serum lipid profile. Further, RRBE modified the level of expression of lipid metabolism-related genes (adipose triglyceride lipase (ATGL), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL), liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1c (SREBP-1c), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and carnitine palmitoyltransferase 1A (CPT1A)) in hepatic or adipose tissues and improved the expression of hepatic high-density lipoprotein cholesterol (HDL-C) cmetabolism-related genes (hepatic lipase (HL) and apolipoprotein A-ǀ (ApoA-ǀ)). RRBE also attenuated markers of liver injury, inflammation, and oxidative stress, accompanied by a modulated expression of inflammatory (nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)), pro-oxidant (p47^phox), and apoptotic (B-cell lymphoma protein 2 (Bcl-2)-associated X and Bcl-2) genes in the liver. High-performance liquid chromatography analyses indicated the presence of protocatechuic acid, γ-oryzanol, vitamin E, and coenzyme Q10 in RRBE. Our data indicate that RRBE alleviates HFD-induced hepatosteatosis, dyslipidemia, and their pathologic complications in part by regulating the expression of key genes involved in lipid metabolism, inflammation, oxidative stress, and apoptosis.

Elaeagnus latifolia (EL) is a wild fruit known for containing several health-promoting compounds. This study aimed to evaluate the effects of EL fruit extract on high-fat diet (HFD)-induced obesity and lipopolysaccharide (LPS)-activated macrophages. Mice fed an HFD and given EL fruit extract for 10 weeks exhibited significantly lower body weight, reduced lipid accumulation, diminished oxidative stress in adipocytes, and decreased macrophage infiltration compared to those not receiving the EL extract. Moreover, the EL fruit extract activated the transcription factors Pparg and Cebpa, initiating adipogenesis and modulating the expression of NF-κB/Nrf-2-induced target genes. This resulted in smaller adipocyte size, reduced inflammation, and less oxidative stress in HFD-fed mice. In vitro, the EL extract induced a shift in macrophage phenotype from M1 to M2, reduced IκBα/NF-κB phosphorylation, and effectively decreased energy production in macrophages by downregulating the expression of several proteins involved in glycolysis and the tricarboxylic acid cycle. This mechanistic study suggests that administering EL fruit extract could be an effective strategy for managing obesity and its associated pathologies.