Spinosin mitigates bone loss in ovariectomy rats by activating the Nrf2/HO-1 pathway, which reduces oxidative stress and improves mitochondrial function.

Postmenopausal osteoporosis (PMOP) is driven by oxidative stress and impaired osteogenic potential. We investigated the protective effects of Spinosin (SPI) using rat bone marrow mesenchymal stem cells (BMSCs) and an ovariectomized (OVX) rat model. Oxidative stress was induced by H2O2. We measured reactive oxygen species (ROS) levels, mitochondrial ultrastructure via transmission electron microscopy (TEM), and the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Results showed that SPI significantly reduced ROS accumulation and preserved mitochondrial integrity and membrane potential. Mechanistically, SPI activated the Nrf2/HO-1 pathway, upregulating osteogenic markers such as RUNX2. In vivo, oral SPI treatment (20 or 40 mg/kg) effectively restored bone volume and microarchitecture in OVX rats. These bone-protective effects were largely abolished by the Nrf2 inhibitor ML385. In conclusion, SPI alleviates oxidative stress-induced BMSC dysfunction and bone loss through Nrf2/HO-1 activation, highlighting its potential as a natural therapeutic agent for PMOP.