Protective effects of Kaempferol on hepatic apoptosis via miR-26a-5p enhancement and regulation of TLR4/NF-κB and PKCδ in a rat model of nonalcoholic fatty liver

Abstract

This study aimed to evaluate kaempferol's, a dietary flavonoid widely present in plants, potential impact on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms. In this study, 60 adult male rats were used and divided into a control group receiving a standard pellet diet, a kaempferol-treated group receiving kaempferol (250 mg/kg), a high-fat diet (HFD) group receiving HFD, and a kaempferol-treated HFD group. At the end of the experiment, the total lipid profile and liver enzymes were assayed in the serum. Additionally, oxidative stress (malondialdehyde and superoxide dismutase), inflammatory (tumor necrosis factor-alpha), apoptotic (caspase 3) markers, and nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR4) concentrations were assayed in the liver tissues. Furthermore, miR-26a and PKCδ gene expression and beclin 1 immunohistochemical expression were determined in liver tissues. Our findings revealed that kaempferol significantly protects against the development of NAFLD in rats as well as inflammatory, oxidative, and apoptotic changes in their liver tissues by inhibiting PKCδ and the TLR-4/NF-κB signaling pathway while enhancing autophagy (Beclin 1 expression) via upregulating miR-26a expression. Accordingly, kaempferol holds promise as a complementary medication for the prevention of NAFLD. Nonetheless, more research is needed to fully understand its additional effects on liver tissue and to develop novel medications that activate miR-26a.

A link between lipid metabolic abnormalities and miRNAs was demonstrated as upregulating miR-26a-5p by kaempferol mitigates the inflammation, apoptosis, and disrupted autophagy via regulating TLR4/NF-κB pathway and PKC in NAFLD.