Wenjuan Zhang1, Kaiyue Xue1, Yongguang Gao1, Ying Huai1, Wei Wang1, Zhiping Miao1, Kai Dang1, Shanfeng Jiang1, Airong Qian2. 1. Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research Center for Special Medicine and Health Systems Engineering, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China. 2. Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research Center for Special Medicine and Health Systems Engineering, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China. Electronic address: qianair@nwpu.edu.cn.
Abstract
AIMS: Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone mass decrease and microstructural degradation, which may increase the risk of bone fracture and leading to high morbidity. Dipsaci Radix (DR), one typical traditional Chinese medicine (TCM), which has been applied in the treatment of OP with good therapeutic effects and few side effects. However, the underlying molecular mechanisms of DR to treat OP have not been fully elucidated. In this study, we aim to dissect the molecular mechanism of DR in the treatment of OP. MATERIALS AND METHODS: A systems pharmacology approach was employed to comprehensively dissect the action mechanisms of DR for the treatment of OP. KEY FINDINGS: 10 compounds were screened out as the potential active ingredients with excellent biological activity based on in silico ADME (absorption, distribution, metabolism and excretion) prediction model. Then, 36 key protein targets of 6 compounds were identified by systems drug targeting model (SysDT) and they were involved in several biological processes, such as osteoclast differentiation, osteoblast differentiation and anti-inflammation. The target-pathway network indicated that targets are mainly mapped in multiple signaling pathways, i.e., MAPK, Tumor necrosis factor α (TNF-α), NF-κb and Toll-like receptor pathways. The in vitro results indicated that the compounds ursolic acid and beta-sitosterol effectively inhibited the osteoclast differentiation. SIGNIFICANCE: These results systematically dissected that DR exhibits the therapeutic effects of OP by the regulation of immune system-related pathways, which provide novel perspective to drug development of OP.
AIMS: Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone mass decrease and microstructural degradation, which may increase the risk of bone fracture and leading to high morbidity. Dipsaci Radix (DR), one typical traditional Chinese medicine (TCM), which has been applied in the treatment of OP with good therapeutic effects and few side effects. However, the underlying molecular mechanisms of DR to treat OP have not been fully elucidated. In this study, we aim to dissect the molecular mechanism of DR in the treatment of OP. MATERIALS AND METHODS: A systems pharmacology approach was employed to comprehensively dissect the action mechanisms of DR for the treatment of OP. KEY FINDINGS: 10 compounds were screened out as the potential active ingredients with excellent biological activity based on in silico ADME (absorption, distribution, metabolism and excretion) prediction model. Then, 36 key protein targets of 6 compounds were identified by systems drug targeting model (SysDT) and they were involved in several biological processes, such as osteoclast differentiation, osteoblast differentiation and anti-inflammation. The target-pathway network indicated that targets are mainly mapped in multiple signaling pathways, i.e., MAPK, Tumor necrosis factor α (TNF-α), NF-κb and Toll-like receptor pathways. The in vitro results indicated that the compounds ursolic acid and beta-sitosterol effectively inhibited the osteoclast differentiation. SIGNIFICANCE: These results systematically dissected that DR exhibits the therapeutic effects of OP by the regulation of immune system-related pathways, which provide novel perspective to drug development of OP.