Liying Wu1, Youguo Hao2, Chuanqiang Dai3, Zhibang Zhang4, Munazza Ijaz5, Sobhy M Ibrahim6, Ghulam Murtaza7, Zhiguang Yao8,9. 1. Department of Orthopedics, Fushun Mining Bureau General Hospital of Liaoning Health Industry Group (The Seventh Affiliated Hospital of China Medical University), Fushun, Liaoning 113008, China. 2. Department of Rehabilitation, Shanghai Putuo People's Hospital, Shanghai 200060, China. 3. Department of Orthopedics, The First People's Hospital of Ziyang, Ziyang, Sichuan 641300, China. 4. Department of Bone and Joint Surgery, Qinghai Fifth People's Hospital, Xining, Qinghai 810007, China. 5. Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan. 6. Department of Biochemistry, College of Science, King Saud University, P.O. Box: 2455, Riyadh 11451, Saudi Arabia. 7. Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan. 8. Graduate School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China. 9. Department of Orthopedics, Haining Hospital of Traditional Chinese Medicine, Haining, Zhejiang 314400, China.
Abstract
PURPOSE: Bone trauma is a clinical condition that afflicts the majority of the world's population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Achyranthis bidentatae Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma. METHODS: An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6. RESULTS: The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7). CONCLUSIONS: The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.
PURPOSE: Bone trauma is a clinical condition that afflicts the majority of the world's population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Achyranthis bidentatae Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma. METHODS: An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6. RESULTS: The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7). CONCLUSIONS: The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.
Authors: Katja Prystaz; Kathrin Kaiser; Anna Kovtun; Melanie Haffner-Luntzer; Verena Fischer; Anna E Rapp; Astrid Liedert; Gudrun Strauss; Georg H Waetzig; Stefan Rose-John; Anita Ignatius Journal: Am J Pathol Date: 2017-11-13 Impact factor: 4.307