Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

Ying Huaia; b; c; 1，Wen-juan Zhang a; b; c; 1，Wei Wang a; b; c，Kai Dang a; b; c，Shan-feng Jiang a; b; c，Dan-ming Lid，Meng Lie，Qiang Haoe，Zhi-ping Miao a; b; c，Yu Li a; b; c; *，Ai-rong Qian a; b; c; *; Ying Huaia; b; c; 1; Wen-juan Zhang a; b; c; 1; Wei Wang a; b; c; Kai Dang a; b; c; Shan-feng Jiang a; b; c; Dan-ming Lid; Meng Lie; Qiang Haoe; Zhi-ping Miao a; b; c; Yu Li a; b; c; *; Ai-rong Qian a; b; c; *

Archive > Volume 13 Issue 3 > 2021,13(3). DOI:10.1016/j.chmed.2021.06.001 Prev Next

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Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

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摘要:

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.

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This work was supported by the National Natural Science Foundation of China under No. 81901917 and No. 31570940; the key grant BKJ17J004 and the Key Research and Development Project of Shaanxi Province under No. 2018SF-363; China’s Post-doctoral Science Fund under No. 2017M623249 and the Fundamental Research Funds for the Central Universities under No. 3102017OQD050.

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Original articles

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment

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