Xi Zheng1, Jingyi Wang1, Junlin Zhou2, Dong Wang2. 1. Department of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China. 2. Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China.
Abstract
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 Ilex cornuta bark are still unknown. This study aimed to explore the effects and mechanisms of Ilex cornuta bark in bone healing. Methods and Results: First, the promoting effects of Ilex cornuta bark on bone healing were verified by the mice femur fracture model as Ilex cornuta bark increased the callus formation and enhanced the biomechanical stability during the bone healing process. Second, the target gene of Ilex cornuta bark in bone healing identified by bioinformatics analysis and immunofluorescence validation was ADORA2A. Third, 410 main compound compositions of Ilex cornuta 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, Ilex cornuta bark water extract was a new plant extract on promoting bone healing; in addition, the mechanism of it might be activating adora2a though Nfkb1.
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 Ilex cornuta bark are still unknown. This study aimed to explore the effects and mechanisms of Ilex cornuta bark in bone healing. Methods and Results: First, the promoting effects of Ilex cornuta bark on bone healing were verified by the mice femur fracture model as Ilex cornuta bark increased the callus formation and enhanced the biomechanical stability during the bone healing process. Second, the target gene of Ilex cornuta bark in bone healing identified by bioinformatics analysis and immunofluorescence validation was ADORA2A. Third, 410 main compound compositions of Ilex cornuta 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, Ilex cornuta bark water extract was a new plant extract on promoting bone healing; in addition, the mechanism of it might be activating adora2a though Nfkb1.
Authors: H M Berman; J Westbrook; Z Feng; G Gilliland; T N Bhat; H Weissig; I N Shindyalov; P E Bourne Journal: Nucleic Acids Res Date: 2000-01-01 Impact factor: 16.971
Authors: Paul Shannon; Andrew Markiel; Owen Ozier; Nitin S Baliga; Jonathan T Wang; Daniel Ramage; Nada Amin; Benno Schwikowski; Trey Ideker Journal: Genome Res Date: 2003-11 Impact factor: 9.043
Authors: Jonathan M Bekisz; Roberto L Flores; Lukasz Witek; Christopher D Lopez; Christopher M Runyan; Andrea Torroni; Bruce N Cronstein; Paulo G Coelho Journal: J Craniomaxillofac Surg Date: 2017-11-21 Impact factor: 2.078
Authors: Christopher D Lopez; Jonathan M Bekisz; Carmen Corciulo; Aranzazu Mediero; Paulo G Coelho; Lukasz Witek; Roberto L Flores; Bruce N Cronstein Journal: Adv Drug Deliv Rev Date: 2018-06-18 Impact factor: 15.470
Authors: Stephen K Burley; Charmi Bhikadiya; Chunxiao Bi; Sebastian Bittrich; Li Chen; Gregg V Crichlow; Jose M Duarte; Shuchismita Dutta; Maryam Fayazi; Zukang Feng; Justin W Flatt; Sai J Ganesan; David S Goodsell; Sutapa Ghosh; Rachel Kramer Green; Vladimir Guranovic; Jeremy Henry; Brian P Hudson; Catherine L Lawson; Yuhe Liang; Robert Lowe; Ezra Peisach; Irina Persikova; Dennis W Piehl; Yana Rose; Andrej Sali; Joan Segura; Monica Sekharan; Chenghua Shao; Brinda Vallat; Maria Voigt; John D Westbrook; Shamara Whetstone; Jasmine Y Young; Christine Zardecki Journal: Protein Sci Date: 2021-11-06 Impact factor: 6.725