Catalpol improves senile osteoporosis by promoting osteogenesis and inhibiting bone resorption through the PI3K/AKT signaling pathway

<title>Abstract</title> <p>Senile osteoporosis (SOP) is core pathology is the imbalance between bone formation and bone resorption, which leads to reduced bone mass and increased bone fragility. Catalpol possesses various biological activities such as antioxidant and anti-inflammatory effects. However, the mechanism by which it improves SOP remains unclear. This study aims to clarify the mechanism of catalpol in improving SOP through the PI3K/AKT signaling pathway. 24 SPF-grade male SD rats were randomly divided into four groups: normal control group, model group, experimental group, and positive control group. Micro-CT, HE, TRAP staining, immunohistochemistry, ELISA, and Western blot were used to detect relevant indicators. The results showed that after catalpol intervention, the bone microstructure parameters of the rat femur, such as BMD and Tb.N were significantly increased, while Tb.Sp was decreased. The number of osteoblasts was increased, and the number of osteoclasts was decreased. In the serum, the level of the bone formation marker PINP was elevated, and the level of the bone resorption marker β-CTX was reduced. In the bone tissue, the expression of osteogenic marker proteins was upregulated, and the expression of osteoclastic marker proteins was downregulated. Meanwhile, the expression of PI3K protein and the ratio of P-AKT to AKT were significantly increased. The above results indicate that catalpol can bidirectionally regulate bone metabolism by activating the PI3K/AKT signaling pathway. It promotes bone formation, inhibits bone resorption, restores bone homeostasis, and improves SOP, thereby holding promise as a potential candidate drug for the clinical prevention and treatment of SOP.</p>