Luteolin’s Potential in Managing Osteoporosis and Bone Metabolism Disorders: Preclinical Insights

Jianqiang Du,1,2,* Wenxiu Qin,2,* Fayan Wen,3,* Dan Zhao,3 Xuesong Yin,3 Ziyu Guo,2 Qijing Feng,1 Enpeng Gu,1 Zhicheng Pan,4 Linjue Wang1 1Department of Orthopedics, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Graduate School, Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China; 4Department of Orthopedics, Binhai New Area Hospital of Traditional Chinese Medicine and the Fourth Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linjue Wang, Email [email protected] Zhicheng Pan, Email [email protected]: Bone homeostasis is a process of dynamic regulation between bone resorption and bone formation, and is the foundation for normal skeletal development in the human body. Once this balance is disrupted, it will lead to bone loss and decreased bone density, profoundly affecting the occurrence and development of bone metabolism-related diseases. For example, common clinical bone metabolic disorders such as osteoporosis, avascular necrosis of the femoral head, and alveolar bone resorption. However, current treatments for bone metabolism-related diseases often have certain limitations, which has driven the development of complementary medicine that helps maintain bone health. Luteolin is a natural flavonoid compound renowned for its exceptional medicinal value and is often used to treat various diseases. In vitro studies indicate that luteolin not only protects osteoblast activity and promotes their osteogenic differentiation, but also inhibits osteoclast activation and their bone resorption function. Simultaneously, it regulates the osteogenic-adipogenic differentiation capacity of bone marrow mesenchymal stem cells, thereby promoting bone formation. Furthermore, Furthermore, in vivo studies indicate that luteolin significantly enhances parameters such as bone mass, trabecular thickness, and density in animal models of bone metabolic disorders, thereby promoting bone remodeling. In terms of mechanisms, luteolin may regulate signaling pathways related to bone metabolism, such as the PI3K/Akt, Wnt, RANKL/RANK/OPG, Nrf2, ERK and JAK/STAT pathways, to inhibit oxidative stress, reduce inflammatory responses, regulate cell death, and modulate the immune microenvironment. Additionally, we explored the pharmacokinetics of luteolin and the current status of drug delivery systems, including luteolin-loaded nanoparticles, biomimetic hydrogels, and porous scaffolds. These systems have effectively achieved controlled release of luteolin, providing drug delivery solutions with clinical translation potential for bone defect repair. The above evidence provides a solid foundation for future applications in bone metabolic homeostasis management and treatment based on luteolin.Keywords: luteolin, bone formation, bone resorption, cell model, animal model, molecular mechanism, pharmacokinetics