Targeting Mitochondrial Dysfunction to Treat Diabetic Osteoporosis: Role of Neoprzewaquinone A.
Abstract
BACKGROUND: Diabetic osteoporosis (DMOP) involves impaired bone formation driven by mitochondrial dysfunction and osteoblast apoptosis. Current treatments do not address these mechanisms.
OBJECTIVE: To evaluate whether Neoprzewaquinone A (NEO), a natural compound from Salvia miltiorrhiza, can protect bone by restoring mitochondrial integrity and activating survival signaling.
METHODS: Bioinformatics, molecular docking, and biophysical assays were combined with in vitro and in vivo studies. Mouse osteoblasts were exposed to glucolipotoxic conditions, and DMOP was induced in C57BL/6 mice. NEO's effects on mitochondrial morphology, mitochondrial membrane potential, ATP production, ROS, apoptosis markers, and PI3K/AKT/mTOR signaling were assessed using imaging, flow cytometry, western blotting, and micro-CT.
RESULTS: Glucolipotoxic stress caused mitochondrial damage, ROS accumulation, and suppression of ELF5/PRKD2 and PI3K/AKT/mTOR signaling. NEO bound PRKD2 with high affinity (KD ≈ 10⁻6 M), restored pathway activation, reduced ROS, attenuated HGPA-induced mitochondrial depolarization, restored ATP levels, and preserved mitochondrial ultrastructure. In diabetic mice, oral NEO improved bone mineral density, trabecular architecture, and mechanical strength without detectable toxicity.
CONCLUSION: NEO mitigates diabetic bone loss by rescuing mitochondrial function and activating the ELF5/PRKD2/PI3K/AKT/mTOR axis. These findings highlight mitochondrial protection as a promising…
Read the paper
Related studies
- Development of a crushable foam model for human trabecular bone
- Data-driven motion compensation in HR-pQCT.
- Modeling of structure, quality, and function in the orthodontic patient
- Exploring the mechanism of Heidihuang Pill in the treatment of osteoporosis based on network pharmacology, molecular docking, and experimental validation
- Effect of fabric on the accuracy of computed tomography-based finite element analyses of the vertebra
- Use of interventions involving virtual reality tasks during the climacteric: a systematic review
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.