Cornus Officinalis Iridoid Glycosides Protect against Chronic Renal Failure in Rats by Activating the Nrf2-antioxidant Pathway

Abstract

Objective: To investigate the therapeutic effects of Cornus officinalis iridoid glycosides (CIG) on rats with chronic renal failure (CRF).

Methods: CRF was induced in adult male Sprague Dawley rats by nephrectomy. The rats were randomly divided into six groups: sham, sham+high-dose CIG (120 mg/kg/d for 14 days), CRF, CRF+low-dose CIG (60 mg/kg/d for 14 days), CRF+high-dose CIG, and CRF+high-dose CIG+ML385 (an inhibitor of nuclear factor erythroid 2-related factor 2 (Nrf2), single administration at 30 mg/kg). The pathohistological changes in renal tissues were evaluated with histological staining. The biomarker levels of renal function, oxidative stress, inflammation, and apoptosis, as well as Nrf2 expression in renal tissues were determined.

Results: The rats in the sham and sham+high-dose CIG groups showed normal renal tissues. The rats in the CRF group displayed severe renal tissue damage/fibrosis and elevated biomarkers of renal dysfunction, which were accompanied by decreased nuclear and cytoplasmic Nrf2 expression and elevated levels of oxidative stress, inflammatory, and apoptotic markers in renal tissues. CIG treatment of CRF rats attenuated renal tissue damage and fibrosis, with the high-dose drug showing more significant improvements. The high-dose CIG also restored renal function in CRF rats, upregulated Nrf2, and downregulated oxidative stress, inflammatory, and apoptotic markers in renal tissues. These effects of high-dose CIG on CRF rats were reversed by ML385.

Conclusions: CIG activates the Nrf2-antioxidant pathway to ameliorate oxidative and inflammatory renal tissue damage and restore renal function in CRF rats.

Keywords: Cornus officinalis iridoid glycosides; chronic renal failure; inflammation; nuclear factor erythroid 2 (NF-E2)-related factor 2; oxidative stress.