<i>Eucommia ulmoides</i> extract regulates oxidative stress to maintain calcium homeostasis and improve diabetic osteoporosis

Diabetic osteoporosis (DOP) is a secondary disease that severely affects the health and quality of life of patients with diabetes mellitus. This study aimed to explore the bone protective effect of aqueous extract of <i>Eucommia ulmoides</i> (EUL) in DOP mice. DOP mice were established using a high-sugar, high-fat diet and streptozotocin (STZ) (35 mg/kg for three consecutive days), and the EUL aqueous extract (2.5 g/kg/day) was orally administered for 6 weeks. The serum levels of oxidative stress-related factors, calcium, and phosphorus were assessed using biochemical assays. The osteoprotective effect of EUL was assessed using micro-computer tomography, three-point bending assay, histological analysis, and immunoblotting. Quantitative real-time polymerase chain reaction and western blotting were performed to detect the expression levels of calcium transport channel factors in the kidney and small intestine tissues. Furthermore, the expression levels of nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>) and heme oxygenase-1 (<i>HO-1</i>) in the femur, kidney, and small intestine tissues were detected using western blotting and quantitative real-time polymerase chain reaction. EUL aqueous extract reduced blood glucose levels, increased body weight, and relieved symptoms in DOP mice (<i>p</i> < .05). It also increased bone mineral density, improved the bone microstructure, decreased the number of femoral osteoclasts, and increased the expression of femoral Runx2 and Bmp2 in DOP mice (<i>p</i> < .01). After 6 weeks of EUL aqueous extract administration, serum levels of SOD, CTA, calcium, and phosphorus were upregulated, whereas MDA levels were decreased (<i>p</i> < .01). The aqueous EUL extract also upregulated the expression of TRPV5, PMCA-1b, and CaBP-9 k in the kidney and small intestine of DOP mice (<i>p</i> < .01). Furthermore, the expression of <i>Nrf2</i> and <i>HO-1</i> in the kidney, small intestine, and femur tissues was increased (<i>p</i> < .01). EUL aqueous extract reduced blood glucose levels in DOP mice and regulated oxidative stress through the <i>Nrf2/HO-1</i> pathway, thereby maintaining calcium homeostasis and ultimately improving bone quality. Our study suggested that EUL aqueous extract may be effective in the treatment of DOP.