Mechanism of traditional Chinese medicine Bai Zhi in preventing microgravity induced bone loss based on network pharmacology and transcriptomics
10.16289/j.cnki.1002-0837.2024.04005
- VernacularTitle:基于网络药理学与转录组学探究白芷抗失重性骨质流失机制
- Author:
Xuechao LIANG
1
;
Ye TIAN
;
Kang RU
;
Bo SANG
;
Rui LIANG
;
Airong QIAN
Author Information
1. 西安市特种医学与健康工程重点实验室,西北工业大学生命科学学院,西安 710072
- Keywords:
microgravity;
bone loss;
transcriptome sequencing;
bai zhi;
network pharmacology
- From:Space Medicine & Medical Engineering
2024;35(4):228-234
- CountryChina
- Language:Chinese
-
Abstract:
Objective In this study,we investigated the active ingredients,targets and molecular mechanisms of Bai zhi based on network pharmacology and mRNA transcriptome sequencing technology for the treatment of microgravity induced bone loss,with a view to providing new therapeutic strategies for microgravity induced bone loss diseases.Methods Investigating the antagonistic effect of the traditional Chinese medicine Bai zhi on microgravity induced bone loss by constructing a hindlimb unloading mice model.18 healthy male mice were randomly divided into Control,HLU and HLU+BZ groups,6 mice in each group,and the effects of Bai zhi on the bone mineral density of the model mice were evaluated after 28 d of continuous gavage.Screening the active ingredients and targets of Bai zhi through TCMSP,Genecards,OMIM,TTD,DisGeNET and other network pharmacology databases.A hindlimb tail suspension unloading animal(HLU)model was established,and the differentially expressed genes(DEGs)responding to mechanical unloading were analyzed using transcriptome sequencing methods,and the targets of Bai zhi active ingredients intersected with the targets of the differentially expressed genes responding to mechanical unloading,so that the core gene targets of Bai zhi for intervening in weightlessness bone loss could be obtained;Construction of Bai zhi component-target protein interaction network(PPI)using String database and Cytoscape software,and enrichment and analysis of key signaling pathways of Bai zhi for treating microgravity induced bone loss using R Studio software.Results Bai zhi effectively restored bone loss in hindlimb tail suspension mice.By quantitative analysis of bone mineral density scanning of hindlimb tail suspension mice,the results showed that Bai zhi significantly restored the loss of bone mineral density in the model mice(P?0.001),Bai zhi has obvious improvement effect on mirogravity induced mice bone loss.10 kinds of Bai zhi effective active ingredients were obtained through the network pharmacology database screening,306 components of the action target,1751 osteoporosis-related disease targets,and 33 disease drug common targets were obtained by drawing the intersection of Wayne's diagram calculation.Through target intersection with transcriptome sequencing differentially expressed genes under simulated microgravity conditions,32 core genes of Bai zhi for intervening in microgravity induced bone loss were obtained,including nuclear transcription factor(JUN),Toll-like receptor 4(TLR4),capsaicin receptor(TRPV1),and so on;Enrichment analysis of the 32 core genes was performed,and the results of GO functional enrichment analysis showed that a total of 194 GO terms were obtained,including 123 biological process(BP)terms,which mainly included insulin-like growth factor receptor,glucose homeostasis in vivo,and negative regulation of gene expression;28 Molecular Function(MF)terms,including RNA polymerase II transcription factor activity,ligand-activated sequence-specific DNA binding,and transcription factor binding;there were 43 cellular component(CC)terms,including cytoplasmic membrane,receptor complex,euchromatin,etc.The results of KEGG enrichment analysis indicated that Bai zhi may be involved in the regulation of insulin-like factor,HIF-1 hypoxic stress,AMPK and other signaling pathways to play a therapeutic function for microgravity induced bone loss.Conclusion under simulated microgravity conditions,the effective active ingredients of Bai zhi may inhibit the accumulation of glycosylation end products(AGEs),oxidative stress damage,and the production of inflammatory factors induced by microgravity stress by regulating the expression of differential genes in response to mechanical unloading,and then participate in osteoblast differentiation in the bone microenvironment to alleviate the occurrence of microgravity induced bone loss diseases.