Targeted activation of Nrf2/HO‐1 pathway by Corynoline alleviates osteoporosis development

Oxidative stress is preferentially treated as a risk factor for the development and progression of osteoporosis. Corynoline as a component of Corydalis bungeana Turcz presents antioxidative and anti‐inflammatory properties. In the present study, the effects of Corynoline on osteoblasts following hydrogen peroxide (H2O2)‐induced injury were evaluated accompanied by the investigation of the molecular mechanisms involved. It was found that Corynoline downregulated the intracellular reactive oxygen species (ROS) generation and restored the osteogenic potential of the disrupted osteoblasts by H2O2 exposure. Furthermore, Corynoline was revealed to activate the Nrf2/HO‐1 signaling pathway, while ML385 (an Nrf2 inhibitor) would prevent the Corynoline‐mediated positive effects on the disrupted osteoblasts. In terms of the animal experiments, Corynoline treatment contributed to a significantly alleviated bone loss. These findings indicate that Corynoline may significantly attenuate the H2O2‐induced oxidative damage of osteoblasts via the Nrf2/HO‐1 signaling pathway, providing novel insights to the development of treatments for osteoporosis induced by oxidative injury. Corynoline could upregulate the antioxidative enzyme expression in H2O2‐treated osteoblasts by activating the Nrf2 pathway, reducing the negative effect of oxidative stress, and strengthening the function of osteoblasts. The in vitro experiment results also showed that Corynoline delayed osteoporosis progression in the rat model and restored Nrf2 in situ expression. Overall, Corynoline could activate the Nrf2 pathway and mitigate or suppress osteoporosis‐related bone loss through the Nrf2 pathway, showing promise as a potential treatment for osteoporosis.