The Extract of Bark Promotes Bone Healing by Activating Adenosine A2A Receptor

Introduction: Bone fracture is a common reason causing human disability. The delay union and nonunion rates are approximately 5-10% despite patients receiving active treatment. Currently, there is a limited number of drugs directly accelerating bone healing, especially direct extracts from plants. Moreover, the pharmacological effects of bark are still unknown. This study aimed to explore the effects and mechanisms of bark in bone healing.

Methods And Results: First, the promoting effects of bark on bone healing were verified by the mice femur fracture model as bark increased the callus formation and enhanced the biomechanical stability during the bone healing process. Second, the target gene of bark in bone healing identified by bioinformatics analysis and immunofluorescence validation was . Third, 410 main compound compositions of bark were explored by a non-target metabolomic analysis, where 190 of them were neg ion mode, and 220 were pos ion mode. Molecular docking was used to predict the regulatory effect of the compounds on adora2a (adenosine A2A receptor), and ursonic acid had the lowest binding energy with adora2a. Finally, nfkb1 was the transcription factor (TF) of adora2a, and ursonic acid also had the lowest binding energy by bioinformatic analysis and molecular docking.

Conclusion: Overall, bark water extract was a new plant extract on promoting bone healing; in addition, the mechanism of it might be activating adora2a though Nfkb1.