Rosmarinic acid alleviates renal tubular injury in obesity-related hypertension by inhibiting the IL-18R1/MYD88/IRAK4 pathway.

Renal tubular injury induced by pro-inflammatory cytokines is the key pathological basis for the progression of obesity-related hypertensive (OBH) nephropathy. Rosmarinic acid (RA) is an important active ingredient in many traditional Chinese medicines and exhibits a variety of pharmacological properties in the treatment of kidney diseases. Further work is needed to understand the underlying molecular mechanisms. In this study, the results showed that in OBH rats, RA significantly decreased blood pressure and Lee index, and improved pathological injury of the renal tubulointerstitial region. Luminex liquid chip assay revealed high levels of IL-18 in the circulation of OBH rats, and that RA had an inhibitory effect on this pro-inflammatory marker. Treatment with RA attenuated the levels of IL-18R1, MYD88, IRARK4, p-IKKα and p-NF-κB proteins and improved the injury and inflammatory response of renal tubules both in vivo and in vitro. The same effect was also observed in NRK-52E cells stimulated with RA-treated rat serum. In vitro, further results revealed that the inhibitory effects of RA on the MYD88/IRAK4/NF-κB pathway and inflammatory injury in MRK-52E cells were blocked in the presence of IL-18R1 overexpression, but were enhanced in the presence of IL-18 neutralizing antibodies. In conclusion, RA alleviates renal tubular injury in OBH rats by inhibiting IL-18-mediated activation of IL-18R1/MYD88/IRAK4 pathway, thereby delaying the progression of OBH-induced kidney disease.