Torularhodin bilosomes attenuate high-fat diet-induced chronic kidney disease in mice by regulating the TLR4/NF-κB pathway

Abstract

Torularhodin is a carotenoid that exerts beneficial effects on chronic kidney disease (CKD), which is strongly linked to a high-fat diet (HFD), however, its functional properties have not yet been fully determined. In this study, torularhodin bilosomes, which feature good processing properties and physical stability, were chosen for delivery. We evaluated their effect on mice with CKD induced by HFD and determined the relevant mechanisms. In HFD-fed mice, both structural and functional renal injury was observed, including significant increases in BUN, SCr, urinary protein levels, capillary basement membrane thickening, and inflammatory cell infiltration. The results showed that SOD content, GSH-px content, and CAT activity were all significantly higher, while the MDA level was significantly lower in the tor-emu and tor-bilo groups, indicating that torularhodin effectively alleviated oxidative stress. In addition, the expression of the inflammatory factors TNF-a, IL-6, and IL-1β was reduced in the torularhodin group compared with the model group, and both the transcription and expression of the TLR4, MyD88, TIRAP, TRIF, and NF-κB proteins related to the TLR4/NF-κB pathway were reduced. Mechanistically, torularhodin reduced the renal inflammatory response by decreasing TLR4 protein expression and the signaling of proteins such as MyD88, as well as preventing NF-κB from undergoing dissociation, reducing its transcriptional activity, and decreasing the release of downstream pro-inflammatory mediators. In conclusion, torularhodin bilosomes can alleviate high-fat diet-induced CKD in mice by modulating the TLR4/NF-κB pathway. This result further deepens the understanding of torularhodin activity and confirms the role of torularhodin as an effective health supplement.