Scutellarin Prevents Nonalcoholic Fatty Liver Disease (NAFLD) and Hyperlipidemia via PI3K/AKT-Dependent Activation of Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2) in Rats

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism.Material/MethodsSprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing. Enzyme activity assay, immunofluorescence, Western blot, and quantitative RT-PCR were performed to analyze the factors of the oxidant/antioxidant system and pathway.ResultsAfter the high-fat diet and chronic stress administration for 12 weeks, serum and liver lipid metabolism of treatment groups with the different doses of SCU effectively improved and the degree of oxidative damage reduced. Using Western blot assay and immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins significantly increased after SCU treatment for 4 weeks (P<0.01). The hepatic mRNA expression of HO-1, NQO1, and Nrf2 in SCU treatment groups was upregulated significantly through quantitative RT-PCR assay (P<0.05). However, compared to the positive control group, no difference was detected in the SCU (100 or 300 mg/kg) groups (P>0.05). These results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress.ConclusionsThe antioxidant effects of SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2 nuclear translocation, which increases expression of HO-1 and NQO1. We therefore suggest that breviscapine may be a potentially useful therapeutic strategy for NAFLD and hyperlipidemia.

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

“…Western blotting demonstrated that miR-199a-3p promoted the expression of LC3BII, suggesting that miR-199a-3p stimulates the autophagy of HUVECs. The PI3K/AKT signaling pathway is associated with the physiological and pathological processes of the body and has important regulatory functions for cell survival, apoptosis and the synthesis and secretion of inflammatory factors (36). It has been reported that PI3K/AKT and its downstream NF-κB signaling pathway promote proliferation, migration and tube formation in endothelial cells (37).…”

The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches

“…In addition, a modulator of PPARγ, apigenin, was also revealed to attenuate NAFLD by Nrf2-associated regulation of oxidative stress and hepatocyte lipid metabolism (Feng et al, 2017). Moreover, for the prevention of NAFLD, scutellarin, which is a natural drug with active components of breviscapine, was shown to be effective by enhancing the Nrf2-mediated antioxidant system in high-fat diet- and chronic stress-subjected rats (Fan et al, 2017).…”

Scutellarin Exerts Hypoglycemic and Renal Protective Effects in db/db Mice via the Nrf2/HO-1 Signaling Pathway

“…, possesses pharmacological properties such as anti-inflammation [16], antioxidant effects [17], and the inhibition of adipogenesis [18]. SCU exerts antioxidant effects via Nrf2 nuclear translocation and has been found to enhance the expression levels of heme oxygenase 1 (HO-1) [19]. SCU-loaded Chit-DC-VB12 nanoparticles have been found to downregulate the central retinal artery resistivity index and angiogenesis-related proteins' expressions of retinas in type 2 diabetic rats [20].…”