Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784648463286272000
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
work_keys_str_mv AT zhanghuihao integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT zhouchengcong integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT zhangzhiguo integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT yaosai integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT bianyishan integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT fufangda integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT luohuan integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT liyan integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT yanshuxin integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT geyuying integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT chenyuying integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT zhankunyu integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT yueming integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT duweibin integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT tiankun integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT jinhongting integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT lixiaofeng integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT tongpeijian integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT ruanhongfeng integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis
AT wuchengliang integrationofnetworkpharmacologyandexperimentalvalidationtoexplorethepharmacologicalmechanismsofzhuanggubusuiformulaagainstosteoporosis