Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology

Dong-hao GAN; De-qiang CHEN; Peng FENG; Zhan-wang XU

doi:10.13422/j.cnki.syfjx.20191239

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Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology

Data Mining | 更新时间：2021-02-09

- Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 13, Pages: 186-191(2019)
- 作者机构：
  
  1.山东中医药大学，济南　 250355；
  2.山东中医药大学　附属医院，济南　 250014
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191239
  CLC： R285; R274; R714.257; R592
- Received：08 December 2018，
  
  Published Online：05 March 2019，
  
  Published：05 July 2019
- 稿件说明：
移动端阅览
Dong-hao GAN, De-qiang CHEN, Peng FENG, et al. Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 186-191.
DOI：

Dong-hao GAN, De-qiang CHEN, Peng FENG, et al. Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 186-191. DOI： 10.13422/j.cnki.syfjx.20191239.

摘要

目的：

通过网络药理学思路，预测骨碎补活性成分的作用靶点，结合骨质疏松(OP)相关靶点进行映射，拓扑出相互作用的关键节点进行富集分析，全方位探讨骨碎补抗OP的药理作用机制。

方法：

首先，在中药系统药理学数据库和分析平台(TCMSP)中基于药代动力学特征筛选出骨碎补的主要活性成分，并使用有机小分子生物活性数据库(PubChem)和Swiss Target Prediction数据库根据二维或三维结构相似性预测出相关作用靶点，然后通过人类孟德尔遗传数据库(OMIM)和Pubmed文本挖掘已知的OP治疗靶点，结合预测靶点导入String数据库构建骨碎补治疗OP靶点相互作用网络图，借助CytoNCA软件根据相关节点参数拓扑出相互作用的关键节点，再次导入String构建蛋白质相互作用网络图，最后通过DAVID数据库对关键节点进行生物功能及代谢通路分析。

结果：

筛选出16个骨碎补活性成分，根据靶点预测技术预测出相关靶点118个；经过文本挖掘检索出OP相关靶点316个，根据String网络数据库构建蛋白相互作用网络，经CytoNCA拓扑后，筛选出关键节点97个，富集分析显示骨碎补可能通过多条通路，从增殖、分化、免疫、氧化应激等多个方面，对干细胞、成骨细胞、破骨细胞、免疫细胞等产生调控作用。

结论：

基于网络药理学研究表明，骨碎补可能通过直接或间接作用靶点，参与调控多条主要信号通路，影响多类细胞的增殖、分化，从而起到抗OP的作用，为阐释其抗骨质疏松的物质基础与作用机制提供了科学依据。

Abstract

Objective:

To predict the target of active components of Drynariae Rhizoma by the network pharmacology

map related targets of osteoporosis (OP)

and analyze key nodes of interaction topologically

so as to comprehensively explore the pharmacological mechanism of anti-op of osteoclasts.

Method:

Firstly

the main active components of Drynariae Rhizoma were screened out from TCMSP based on the pharmacokinetic characteristics

and the related targets were predicted by Pubchem and Swiss Target Prediction database according to the Two-dimensional/Three-dimensional(2D/3D)structural similarity. Then

through Online Mendelian Inheritance in Man (OMIM) and Pubmed text

known OP therapeutic targets were mined

based on putative targets

String database was imported to build Drynariae Rhizoma treatment target OP interaction network diagram. With the help of CytoNCA software

the interaction key nodes were topologically identified according to relevant node parameters

and then imported into String database to build the protein interaction network graph. Finally

biological functions and metabolic pathways of key nodes were analyzed through DAVID database.

Result:

Sixteen active components of Drynariae Rhizoma were screened out

and 118 related targets were predicted according to the target prediction technique. Totally 316 known therapeutic targets for OP were retrieved. The protein interaction network was constructed according to the String network database. A total of 97 key nodes were screened via CytoNCA topology. The enrichment analysis showed that Drynariae Rhizoma may play an anti-osteoporosis role by regulating stem cells

osteoblasts

osteoclasts and immune cells through multiple signaling pathways in aspects of proliferation

differentiation

immunity and oxidative stress.

Conclusion:

Studies based on network pharmacology have shown that Drynariae Rhizoma may play an anti-op role through direct or indirect targets and multiple major signaling pathways and affect the proliferation and differentiation of multiple types of cells

in order to provid a scientific basis for explaining the material basis and mechanism of Drynariae Rhizoma's anti-osteoporosis effect.

关键词

Keywords

references

Rachner T D , Khosla S , Hofbauer L C . Osteoporosis: now and the future [J]. Lancet , 2011 , 377 ( 9773 ): 1276 - 1287 .

Twinkle G , Nilanjan D , Sabiha I . The prevention and therapy of osteoporosis: a review on mmerging trends from hormonal therapy to synthetic drugs to plant-based bioactives [J]. J Diet Suppl , 2018 , doi: 10.1080/19390211.2018.1472715 http://doi.org/10.1080/19390211.2018.1472715 .

JIA M , NIE Y , CAO D P , et al . Potential antiosteoporotic agents from plants: a comprehensive review [J]. Evid Based Complement Alternat Med , 2012 , doi: 10.1155/2012/364604 http://doi.org/10.1155/2012/364604 .

吴慧平，陈建伟，许婷婷，等．骨碎补与夜交藤组合物对α-糖苷酶活性的影响 [J]．中国实验方剂学杂志， 2012 ， 18 ( 5 )： 181 - 184 ．

陈云刚，谭国庆，任维龙，等．骨碎补含药血清经wnt/β-catenin信号通路对大鼠骨髓间充质干细胞成骨分化的影响 [J]．中国药理学通报， 2017 ， 33 ( 6 )： 830 - 836 ．

薛海鹏，刘国岩，吴燕，等．骨碎补促进骨髓间充质干细胞增殖及成骨分化 [J]．中国矫形外科杂志， 2018 ， 26 ( 11 )： 1035 - 1040 ．

RU J , LI P , WANG J , et al . TCMSP: a database of systems pharmacology for drug discovery from herbalmedicines [J]. J Cheminform , 2014 , 6 ( 1 ): 13 .

LIU H , WANG J , ZHOU W , et al . Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice [J]. J Ethnopharmacol , 2013 , 146 ( 3 ): 773 - 793 .

XU X , ZHANG W X , HUANG C , et al . A novel chemometric method for the prediction of human oral bioavailability [J]. Int J Mol Sci , 2012 , 13 ( 12 ): 6964 - 6982 .

LI J , ZHAO P , LI Y , et al . Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease [J]. Sci Rep , 2015 , doi: 10.1038/srep15290 http://doi.org/10.1038/srep15290 .

WANG S , WANG H , LU Y . Tianfoshen oral liquid: a CFDA approved clinical traditional Chinese medicine, normalizes major cellular pathways disordered during colorectal carcinogenesis [J]. Oncotarget , 2017 , 8 ( 9 ): 14549 .

WANG Y L , Bryant S H , CHENG T , et al . Pubchem bioassay: 2017 update [J]. Nucleic Acids Res , 2017 , 45 ( D1 ): 955 - 963 .

Gfeller D , Grosdidier A , Wirth M , et al . Swiss target prediction: a web server for target prediction of bioactive small molecules [J]. Nucleic Acids Res , 2014 , 42 ( Web1 ): 32 - 38 .

Shannon P , Markiel A , Ozier O , et al . Cytoscape: a software environment for integrated models of biomolecular interaction networks [J]. Genome Res , 2003 , 13 ( 11 ): 2498 - 2504 .

Hamosh A , Scott A F , Amberger J , et al . Online mendelian inheritance in man (omim), a knowledgebase of human genes and genetic disorders [J]. Nucleic Acids Res , 2001 , 30 ( 1 ): 52 - 55 .

Szklarczyk D , Morris J H , Cook H , et al . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible [J]. Nucleic Acids Res , 2017 , 45 ( D1 ): D362 - D368 .

TANG Y , LI M , WANG J , et al . CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks [J]. Biosystems , 2015 , 127 : 67 - 72 .

LI S , ZHANG Z Q , WU L J , et al . Understanding zheng in traditional Chinese medicine in the context of neuro-endocrine-immune network [J]. IET Syst Biol , 2007 , 1 ( 1 ): 51 - 60 .

WANG Y , LIU Z , LI C , et al . Drug target prediction based on the herbs components: the study on the multitargets pharmacological mechanism of qishenkeli acting on the coronary heart disease [J]. Evid Based Complement Alternat Med , 2012 , 2012 ( 2 ): e698531 .

WEI M , YANG Z , LI P , et al . Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model [J]. Am J Chin Med , 2007 , 35 ( 4 ): 663 - 667 .

LI L , ZENG Z , CAI G . Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1 [J]. Phytomedicine , 2011 , 18 ( 11 ): 985 - 989 .

Albers J , Keller J , Baranowsky A , et al . Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin [J]. J Cell Biol , 2013 , 200 ( 4 ): 537 - 549 .

WU Q , ZHONG Z M , PAN Y , et al . Advanced oxidation protein products as a novel marker of oxidative stress in postmenopausal osteoporosis [J]. Med Sci Monit , 2015 , 21 : 2428 - 2432 .

Manolagas S C . From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis [J]. Endocr Rev , 2010 , 31 ( 3 ): 266 - 300 .

Ambrogini E , Almeida M , Martin-Millan M , et al . Foxo-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice [J]. Cell Metab , 2010 , 11 ( 2 ): 136 - 146 .

Manolagas S C , Maria A . Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism [J]. Mol Endocrinol , 2007 , 21 ( 11 ): 2605 - 2614 .

CHOU C W , Chiang T I , CHANG I C , et al . Expression levels of estrogen receptor α mRNA in peripheral blood cells are an independent biomarker for postmenopausal osteoporosis [J]. BBA Clin , 2016 , 5 : 124 - 129 .

ZOU W , Izawa T , ZHU T , et al . Talin1 and rap1 are critical for osteoclast function [J]. Mol Cell Biol , 2013 , 33 ( 4 ): 830 - 844 .

XI J C , ZANG H Y , GUO L X , et al . The PI3K/AKT cell signaling pathway is involved in regulation of osteoporosis [J]. J Recept Res , 2015 , 35 ( 6 ): 640 - 645 .

Hye K , Myung-Gyou K , Kang-Hyun L . Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of collagen synthesis and its therapeutic efficacy in osteoporotic bone by back-scattered electron imaging and microarchitecture analysis [J]. Molecules , 2013 , 18 ( 12 ): 15474 - 15489 .

LI G , WANG M , HAO L , et al . Angiotensin Ⅱ induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast [J]. Arch Oral Biol , 2014 , 59 ( 5 ): 513 - 523 .

Choi S W , Son Y J , Yun J M , et al . Fisetin inhibits osteoclast differentiation via downregulation of p38 and c-Fos-NFATc1 signaling pathways [J]. Evid Based Complement Alternat Med , 2012 , 2012 ( 6 ): e810563 .

Britto J M . Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption [J]. Endocrinology , 1994 , 134 ( 1 ): 169 - 176 .

Cray J J , Kameron K , Weinberg S M , et al . Effects of thyroxine exposure on osteogenesis in mouse calvarial pre-osteoblasts [J]. PLoS One , 2013 , 8 ( 7 ): e69067 .

WU J B , Fong Y C , Tsai H Y , et al . Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts [J]. Eur J Pharmacol , 2008 , 588 ( 2/3 ): 333 - 341 .

SONG N , ZHAO Z , MA X , et al . Naringin promotes fracture healing through stimulation of angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats [J]. Chem Biol Interact , 2016 , doi: 10.1016/j.cbi.2016.10.020 http://doi.org/10.1016/j.cbi.2016.10.020 .

LIU M , LI Y , YANG S T . Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells [J]. J Tissue Eng Regen Med , 2017 , 11 ( 1 ): 276 - 284 .

GUO D , WANG J , WANG X , et al . Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu) [J]. J Ethnopharmacol , 2011 , 138 ( 2 ): 451 - 457 .

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