Role and possible mechanism of diosmetin in alleviating nephritis response in MRL/lpr lupus nephritis mice

Abstract

Objective To investigate the protective effect of diosmetin on lupus nephritis and its possible mechanism. Methods Ten C57BL/6 mice were used as control group, and 50 MRL/lpr lupus mice were randomly divided into MRL/lpr group, dexamethasone group, and 3 doses of diosmetin groups (0.25, 0.50 and 1.00 mg/kg). After intraperitoneal injection for 7 d, the serum and kidney tissues of all mice were collected. HE staining was used to observe the morphological changes of the kidneys. Corresponding kits were used to measure the levels of serum creatinine, blood urea nitrogen, and serum anti-double-stranded DNA antibody, as well as the expression levels of IL-1β, IL-6, and TNF-α in the serum and renal tissue. The protein levels of NLRP3, ASC, Caspase-1, IL-1β, p-NF-κB and p-IκBα in renal tissues were detected by Western blotting. Results Compared with the MRL/lpr group, the medium and high dose diosmetin groups and the dexamethasone group had reduced infiltration of inflammatory cells in the kidney tissue, and significantly decreased levels of serum creatinine, blood urea nitrogen and serum anti-double-chain DNA antibody (P < 0.05). Meanwhile, the protein expression levels of IL-1β, IL-6 and TNF-α in the serum and kidney tissues were also significantly decreased (P < 0.05). Compared with the MRL/lpr group, the protein levels of NLRP3, ASC, Caspase-1, IL-1β and p-NF-κB were remarkably decreased (P < 0.05), while that of p-IκBα was notably increased in the medium and high dose diosemetin groups and the dexamethasone group(P < 0.05). Conclusion Diosmetin has a protective effect on the kidney of MRL/lpr mice, and the mechanism may be related to the inhibition of NLRP3 and NF-κB signaling pathway.

Keywords

• diosmetin
• mrl/lpr lupus nephritis
• inflammation
• nlrp3 pathway
• nf-κb pathway