Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

Ying Huai; Wen-Juan Zhang; Wei Wang; Kai Dang; Shan-Feng Jiang; Dan-Ming Li; Meng Li; Qiang Hao; Zhi-Ping Miao; Yu Li; Ai-Rong Qian

doi:10.1016/j.chmed.2021.06.001

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

Chin Herb Med. 2021 Jun 3;13(3):313-331. doi: 10.1016/j.chmed.2021.06.001. eCollection 2021 Jul.

Authors

Ying Huai^{1

2

3}, Wen-Juan Zhang^{1

2

3}, Wei Wang^{1

2

3}, Kai Dang^{1

2

3}, Shan-Feng Jiang^{1

2

3}, Dan-Ming Li⁴, Meng Li⁵, Qiang Hao⁵, Zhi-Ping Miao^{1

2

3}, Yu Li^{1

2

3}, Ai-Rong Qian^{1

2

3}

Affiliations

¹ Laboratory for Bone Metabolism, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
² Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
³ NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
⁴ Department of Radiation Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
⁵ State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

Abstract

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment.

Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis.

Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis.

Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Keywords: asperosaponin VI; betulinic acid; calycosin; drug discovery; hederagenin; luteolin; osteoporosis; systems pharmacology; traditional Chinese medicine.