Morroniside in Cornus officinalis Sieb. et Zucc. protects renal tubular epithelial cells from hypoxia/reoxygenation damage by inhibiting oxidative stress and ferroptosis.

Abstract

Acute kidney injury (AKI) is a critical condition with high morbidity and mortality, often caused by ischemia/reperfusion (I/R) injury. Morroniside (MOR), derived from Cornus officinalis, has anti-inflammatory and antioxidant properties. This study investigates its effects on AKI induced by hypoxia/reoxygenation (H/R) in renal tubular epithelial cells. H/R-induced HK-2 cells were treated with MOR (0.5, 1.0, and 2.0 ‍μM). Cell viability was assessed using CCK-8, and oxidative stress was evaluated via reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. Ferroptosis was examined through GPX4 and ACSL4 expression. The Nrf2/HO-1 signaling pathway was analyzed by Western blotting. Results show that MOR alleviates H/R-induced cell damage and oxidative stress by increasing cell viability, reducing lactate dehydrogenase (LDH) release, ROS, and MDA levels, while enhancing SOD and GSH activities. It also inhibits ferroptosis by upregulating GPX4 and downregulating ACSL4. Additionally, MOR activates the Nrf2/HO-1 signaling pathway. These findings suggest that MOR protects renal tubular epithelial cells from H/R injury by reducing oxidative damage and inhibiting ferroptosis, potentially through the Nrf2/HO-1 pathway.