Chi-Fung Cheng1, Jeff Chien-Fu Lin2, Fuu-Jen Tsai3, Chao-Jung Chen4, Jian-Shiun Chiou5, Chen-Hsing Chou6, Te-Mao Li7, Ting-Hsu Lin8, Chiu-Chu Liao9, Shao-Mei Huang10, Ju-Pi Li11, Jung-Chun Lin12, Chih-Chien Lin13, Bo Ban14, Wen-Miin Liang15, Ying-Ju Lin16. 1. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan. Electronic address: jimmy.bbww@hotmail.com. 2. Department of Statistics, National Taipei University, Taipei, Taiwan; Department of Orthopedic Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: cflin@mail.ntpu.edu.tw. 3. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. Electronic address: d0704@mail.cmuh.org.tw. 4. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address: cjchen@mail.cmu.edu.tw. 5. Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan. Electronic address: lphotoimpact@hotmail.com. 6. Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan. Electronic address: jasing75912@hotmail.com. 7. School of Chinese Medicine, China Medical University, Taichung, Taiwan. Electronic address: leedemaw@mail.cmu.edu.tw. 8. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: t10058@yahoo.com.tw. 9. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: chiuchu0201@gmail.com. 10. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: n3022337@hotmail.com. 11. School of Chinese Medicine, China Medical University, Taichung, Taiwan; Rheumatism Research Center, China Medical University Hospital, Taichung, Taiwan. Electronic address: d888203@gmail.com. 12. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: lin2511@tmu.edu.tw. 13. Department of Cosmetic Science, Providence University, Taichung, Taiwan. Electronic address: chchlin@pu.edu.tw. 14. Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, Jining, Shandong, China. Electronic address: banbo@mail.jnmc.edu.cn. 15. Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan. Electronic address: wmliang@mail.cmu.edu.tw. 16. Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan. Electronic address: yjlin.kath@gmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis is one of the most common bone diseases; it is characterized by bone loss and is a risk factor for hip fracture. Chinese herbal medicines (CHMs) and their related natural compounds have been used for treating many diseases, including bone diseases, since ancient times in China and are regarded as a cost-effective complementary therapy. AIM OF THE STUDY: The goal of this study was to investigate the osteoprotective mechanisms of these three Chinese herbs and their related natural compounds. The effects of CHMs and related natural compounds on RANKL-induced osteoclastogenesis in vitro were investigated. MATERIALS AND METHODS: A network pharmacology method was applied to study CHM-related natural compounds and their osteoporosis targets. In addition, their effect on RANKL-induced osteoclastogenesis in RAW264.7 cells was also investigated in vitro. RESULTS: Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae exhibited protective effects against mortality in hip fracture patients. Furthermore, these three herbs inhibited RANKL-induced TRAP activities and reduced the expression of bone resorption-related genes in RAW264.7 cells. Network analysis of natural compound (ingredient)-target interactions identified 11 natural compounds. Signal pathway analyses suggested that these compounds may target cytokine-cytokine receptor interactions, including RANKL-induced osteoclastogenesis. Five novel natural compounds exhibited reduced RANKL-induced TRAP activities and bone resorption-related gene expression. CONCLUSION: The clinically used CHMs, Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae, and natural compounds obtained from them may suppress RANKL-induced osteoclastogenesis in vitro.
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis is one of the most common bone diseases; it is characterized by bone loss and is a risk factor for hip fracture. Chinese herbal medicines (CHMs) and their related natural compounds have been used for treating many diseases, including bone diseases, since ancient times in China and are regarded as a cost-effective complementary therapy. AIM OF THE STUDY: The goal of this study was to investigate the osteoprotective mechanisms of these three Chinese herbs and their related natural compounds. The effects of CHMs and related natural compounds on RANKL-induced osteoclastogenesis in vitro were investigated. MATERIALS AND METHODS: A network pharmacology method was applied to study CHM-related natural compounds and their osteoporosis targets. In addition, their effect on RANKL-induced osteoclastogenesis in RAW264.7 cells was also investigated in vitro. RESULTS: Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae exhibited protective effects against mortality in hip fracturepatients. Furthermore, these three herbs inhibited RANKL-induced TRAP activities and reduced the expression of bone resorption-related genes in RAW264.7 cells. Network analysis of natural compound (ingredient)-target interactions identified 11 natural compounds. Signal pathway analyses suggested that these compounds may target cytokine-cytokine receptor interactions, including RANKL-induced osteoclastogenesis. Five novel natural compounds exhibited reduced RANKL-induced TRAP activities and bone resorption-related gene expression. CONCLUSION: The clinically used CHMs, Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae, and natural compounds obtained from them may suppress RANKL-induced osteoclastogenesis in vitro.