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Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis
Osteoporosis (OP) is a common skeletal disease, characterized by decreased bone formation and increased bone resorption. As a novel Chinese medicine formula, Zhuanggu Busui formula (ZGBSF) has been proved to be an effective prescription for treating OP in clinic, however, the pharmacological mechani...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831245/ https://www.ncbi.nlm.nih.gov/pubmed/35154014 http://dx.doi.org/10.3389/fendo.2021.841668 |
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author | Zhang, Huihao Zhou, Chengcong Zhang, Zhiguo Yao, Sai Bian, Yishan Fu, Fangda Luo, Huan Li, Yan Yan, Shuxin Ge, Yuying Chen, Yuying Zhan, Kunyu Yue, Ming Du, Weibin Tian, Kun Jin, Hongting Li, Xiaofeng Tong, Peijian Ruan, Hongfeng Wu, Chengliang |
author_facet | Zhang, Huihao Zhou, Chengcong Zhang, Zhiguo Yao, Sai Bian, Yishan Fu, Fangda Luo, Huan Li, Yan Yan, Shuxin Ge, Yuying Chen, Yuying Zhan, Kunyu Yue, Ming Du, Weibin Tian, Kun Jin, Hongting Li, Xiaofeng Tong, Peijian Ruan, Hongfeng Wu, Chengliang |
author_sort | Zhang, Huihao |
collection | PubMed |
description | Osteoporosis (OP) is a common skeletal disease, characterized by decreased bone formation and increased bone resorption. As a novel Chinese medicine formula, Zhuanggu Busui formula (ZGBSF) has been proved to be an effective prescription for treating OP in clinic, however, the pharmacological mechanisms underlying the beneficial effects remain obscure. In this study, we explored the pharmacological mechanisms of ZGBSF against OP via network pharmacology analysis coupled with in vivo experimental validation. The results of the network pharmacology analysis showed that a total of 86 active ingredients and 164 targets of ZGBSF associated with OP were retrieved from the corresponding databases, forming an ingredient-target-disease network. The protein-protein interaction (PPI) network manifested that 22 core targets, including Caspase-3, BCL2L1, TP53, Akt1, etc, were hub targets. Moreover, functional enrichment analyses revealed that PI3K-Akt and apoptosis signalings were significantly enriched by multiple targets and served as the targets for in vivo experimental study validation. The results of animal experiments revealed that ZGBSF not only reversed the high expression of Caspase-3, Bax, Prap, and low expression of Bcl-2 in osteoblasts of the OP mouse model but also contributed to the phosphorylation of Akt1 and expression of PI3K, thereby promoting osteogenesis and ameliorating the progression of OP. In conclusion, this study systematically and intuitively illustrated that the possible pharmacological mechanisms of ZGBSF against OP through multiple ingredients, targets, and signalings, and especially the inhibition of the apoptosis and the activation of PI3K-Akt signaling. |
format | Online Article Text |
id | pubmed-8831245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88312452022-02-12 Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis Zhang, Huihao Zhou, Chengcong Zhang, Zhiguo Yao, Sai Bian, Yishan Fu, Fangda Luo, Huan Li, Yan Yan, Shuxin Ge, Yuying Chen, Yuying Zhan, Kunyu Yue, Ming Du, Weibin Tian, Kun Jin, Hongting Li, Xiaofeng Tong, Peijian Ruan, Hongfeng Wu, Chengliang Front Endocrinol (Lausanne) Endocrinology Osteoporosis (OP) is a common skeletal disease, characterized by decreased bone formation and increased bone resorption. As a novel Chinese medicine formula, Zhuanggu Busui formula (ZGBSF) has been proved to be an effective prescription for treating OP in clinic, however, the pharmacological mechanisms underlying the beneficial effects remain obscure. In this study, we explored the pharmacological mechanisms of ZGBSF against OP via network pharmacology analysis coupled with in vivo experimental validation. The results of the network pharmacology analysis showed that a total of 86 active ingredients and 164 targets of ZGBSF associated with OP were retrieved from the corresponding databases, forming an ingredient-target-disease network. The protein-protein interaction (PPI) network manifested that 22 core targets, including Caspase-3, BCL2L1, TP53, Akt1, etc, were hub targets. Moreover, functional enrichment analyses revealed that PI3K-Akt and apoptosis signalings were significantly enriched by multiple targets and served as the targets for in vivo experimental study validation. The results of animal experiments revealed that ZGBSF not only reversed the high expression of Caspase-3, Bax, Prap, and low expression of Bcl-2 in osteoblasts of the OP mouse model but also contributed to the phosphorylation of Akt1 and expression of PI3K, thereby promoting osteogenesis and ameliorating the progression of OP. In conclusion, this study systematically and intuitively illustrated that the possible pharmacological mechanisms of ZGBSF against OP through multiple ingredients, targets, and signalings, and especially the inhibition of the apoptosis and the activation of PI3K-Akt signaling. Frontiers Media S.A. 2022-01-28 /pmc/articles/PMC8831245/ /pubmed/35154014 http://dx.doi.org/10.3389/fendo.2021.841668 Text en Copyright © 2022 Zhang, Zhou, Zhang, Yao, Bian, Fu, Luo, Li, Yan, Ge, Chen, Zhan, Yue, Du, Tian, Jin, Li, Tong, Ruan and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Zhang, Huihao Zhou, Chengcong Zhang, Zhiguo Yao, Sai Bian, Yishan Fu, Fangda Luo, Huan Li, Yan Yan, Shuxin Ge, Yuying Chen, Yuying Zhan, Kunyu Yue, Ming Du, Weibin Tian, Kun Jin, Hongting Li, Xiaofeng Tong, Peijian Ruan, Hongfeng Wu, Chengliang Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title | Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title_full | Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title_fullStr | Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title_full_unstemmed | Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title_short | Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis |
title_sort | integration of network pharmacology and experimental validation to explore the pharmacological mechanisms of zhuanggu busui formula against osteoporosis |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831245/ https://www.ncbi.nlm.nih.gov/pubmed/35154014 http://dx.doi.org/10.3389/fendo.2021.841668 |
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