Network Pharmacology Analysis of Epimedium in the Treatment of Osteoporotic Fracture

Abstract

Abstract: Objective To identify the the molecular mechanism of epimedium in the treatment of osteoporotic fracture based on network pharmacology. Methods The main active components and targets of epimedium was screened in the Chinese Medicine Computing System Pharmacology Analysis Platform (TCMSP), and a prediction for osteoporotic fracture targets in GeneCards database, OMIM database, PharmGkb database, TTD database and DrugBank database was performed. The common targets of epimedium and osteoporotic fracture were got by Venn diagrams. Cytoscape3.6.1 was used to construct a Chinese medicine-ingredient-disease-target regulation network, then establish a protein-protein interaction network through the STRING data platform, and finally use the R language and Bioconductor platform for gene ontology enrichment analysis and gene interaction (KEGG) pathway analysis. Results The treatment of osteoporotic fracture with epimedium is mainly through 23 active components, 193 key targets and 155 biological signaling pathways. The main active constituents of the drug were quercetin, kaempferol and luteolin. The key targets were AKT1, TP53, Jun, HSP90AA1, CASP3, etc. The key pathway was Lipid and atherosclerosis signaling pathway. Conclusion This study shows the action characteristic of epimedium in the treatment of osteoporotic fracture may be achieved by multi-components, multi-targets and multi-biological signaling pathways through network pharmacology,and it provide a scientific theoretical basis for the further research and experiments．

Key words: traditional Chinese medicine, epimedium, osteoporotic fracture, network pharmacology, mechanism

CLC Number:

R683

ZHANG Wen-zheng, LI Chun-pu, CHEN Lei, GUO Dong-mei, LI Jun, ZHANG Yuan-yuan, WEI Kai-bin, ZHANG Ya. Network Pharmacology Analysis of Epimedium in the Treatment of Osteoporotic Fracture[J]. ZHONGHUA YANGSHENG BAOJIAN, 2024, 42(5): 81-85.

References

[1] LIU J, CURTIS E M, COOPER C, et al.State of the art in osteoporosis risk assessment and treatment[J]. Journal of Endocrinological Investigation, 2019,42(10):1149-1164.
[2] MA Y Z, WANG Y M, LIU Q, et al.2018 China guideline for the diagnosis and treatment of senile osteoporosis[J]. Chin J Gerontol,2019,39(11): 2557-2575.
[3] OUMER K S, LIU Y, YU Q, et al.Awareness of osteoporosis among 368 residents in China: a cross-sectional study[J]. BMC Musculoskelet Disord, 2020,21(1):197.
[4] BEAUDART C, BIVER E, BRUYèRE O, et al. Quality of life assessment in musculo-skeletal health[J]. Aging clinical and experimental research,2018,30(5):413-418.
[5] WANG S J, YUE W, RAHMAN K, et al.Mechanism of treatment of kidney deficiency and osteoporosis is similar by traditional Chinese medicine[J]. Curr Pharm Des,2016,22(3):312-320.
[6] 黄明炜,廖勇敢.淫羊藿总黄酮调节骨代谢作用及药理机制的研究新进展[J].中国骨质疏松杂志,2014,20(4):452-456.
[7] 中华人民共和国药典(2015年版).第1部[M].北京:中国医药科技出版社,2015:526-529.
[8] 杨帆,邓兆智,韩云,等.中药治疗骨质疏松症的用药规律探析[J].广东药学院学报,2003,19(1):70-71.
[9] 宋敏,刘涛,巩彦龙,等.基于中医传承辅助平台系统的骨质疏松症组方用药规律分析[J].中国骨质疏松杂志,2017,23(4):519-523.
[10] 万亚宁,李双蕾,蒋云霞,等.淫羊藿及其复方制剂治疗糖皮质激素性骨质疏松症的研究进展[J].中国骨质疏松杂志,2019,25(5):713-716.
[11] LI S, ZHANG B.Traditional Chinese medicine network pharmacology: theory,methodology and application[J]. Chin J Nat Med,2013,11(2):110-120.
[12] ZHANG R, ZHU X, BAI H, et al.Network pharmacology databases for traditional Chinese medicine: Review and assessment[J]. Frontiers in pharmacology,2019,10:123.
[13] 解晶,李丰,石彬彬,等.系统药理学:TCMSP 解析中医基础理论研究进展[J].世界中医药,2019,14(10):2627-2635.
[14] TAO W, XU X, WANG X, et al.Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease[J]. J Ethnopharmacol,2013,145(1):1-10.
[15] 罗静初. UniProt 蛋白质数据库简介[J]. 生物信息学,2019,17(3):131-144.
[16] FISHILEVICH S, NUDEL R, RAPPAPORT N, et al.Gene Hancer: genome-wide integration of enhancers and target genes in Gene Cards[J]. Database (Oxford),2017,2017:28.
[17] 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.
[18] SZKLARCZYK D, MORRIS JH, 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):D362-362,D368.
[19] YU G, WANG LG, HAN Y, et al.cluster Profiler: an R package for comparing biological themes among gene clusters[J]. OMICS,2012, 16(5):284-287.
[20] GE Q, CHEN L, TANG M, et al.Analysis of mulberry leaf components in the treatment of diabetes using network pharmacology[J]. Eur J Pharmacol,2018,833:50-62.
[21] TOSHIO H W, KOICHIRO O M, MORIHIKO M D, et al.The effects ofselective estrogen receptor modulator treatment following hormone replacement therapy on elderly postmenopausal women with osteoporosis[J]. Nitric Oxide,2016,24(4):919-931.
[22] 卞伟,孙宏,刘凯,等.槲皮素对骨质疏松大鼠骨生物力学性能及骨代谢的影响[J].吉林中医药,2016,3(8):814-817.
[23] YUAN Z, MIN J, ZHAO Y, et al.Quercetin rescued TNF-alpha-induced impairments in bone marrow-derived mesenchymal stem cell osteogenesis and improved osteoporosis in rats[J]. Am J Transl Res,2018,10(12):4313-4321.
[24] 刘军,刘峰,闫楚奇,等.槲皮素对双膦酸盐治疗老年性骨质疏松患者骨代谢指标改善效果的分析[J].中国骨质疏松杂志,2020,26(7):1044-1048.
[25] KIM C J, SHIN S H, KIM B J, et al.The effects of kaempferol-inhibited autophagy on osteoclast formation[J]. Int J Mol Sci,2018,19(1):125.
[26] SHARMA A R, NAM J S.Kaempferol stimulates WNT/β-catenin signaling pathway to induce differentiation of osteoblasts[J]. J Nutr Biochem,2019,74:108228.
[27] 赵晶. 杜仲叶提取物山奈酚对卵巢去势大鼠骨生成的影响及其与mTOR信号通路的关系研究[D].南昌:南昌大学,2019.
[28] ZHAO J, WU J, XU B W, et al.Kaempferol promotes bone formation in part via the mTOR signaling pathway[J]. Mol MedRep,2019,20(6):5197-5207.
[29] KIM T H, JUNG J W, HA B G, et al.The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss[J]. J Nutr Biochem,2011,22(1):8-15.
[30] JING Z, WANG C, YANG Q, et al.Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3β signaling pathway in vivo and in vitro[J]. J Cell Physiol, 2019,234(4):4472-4490.
[31] 黎海霞,许阳,邓凯丽,等.GWGS 芯片整合分析识别外周血细胞中与骨质疏松症相关的枢纽基因[J].生命科学研究,2020,24(2):102-108.
[32] MUKHERJEE A, ROTEEIN P.Selective signaling by Akt1 controls osteob last differentiation and osteoblast-mediated osteo-clast development[J]. Mol Cell Biol,2012,32(2):490-500.
[33] YU T, YOU X M, ZHOU H C, et al.p53 plays a central role in the development of osteoporosis[J]. Aging(Albany NY),2020,12(11):10473-10487.
[34] 武密山,赵素芝,任立中,等.柚皮苷对乳鼠成骨细胞增殖及c-fos、c-jun表达的影响[J].中国药理学通报,2011,27(5):677-681.
[35] LERBS T, CUI L, MUSCAT C, et al.Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures[J]. Stem Cell Reports,2020,14(4):603-613.
[36] YANG X L, CUI Z Z, ZHANG H, et al.Causal link between lipid profile and bone mineral density: A mendelian randomization study[J]. Bone,2019,127: 37-43.
[37] MISHRA B H, MISHRA P P, MNONEN N, et al.Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis:The cardiovascular risk in young finns study[J]. Bone,2019,131:115-160.
[38] 李丽婷. PPARγ2内源性配体对成骨细胞及骨髓细胞骨代谢相关基因表达的影响[D].太原:山西医科大学,2011.
[39] YIN Z, Z W, WU Q, et al. Glycyrrhizic acid suppresses osteoclast differentiation and postmenopausal osteoporosis by modulating the NF-κB, ERK, and JNK signaling pathways[J]. Eur J Pharmacol,2019,859:172550.
[40] 许赫,刘长山,窦建新.骨保护素与动脉粥样硬化的研究进展[J].中国动脉硬化杂志,2017,25(9):968-972.
[41] 王寓平. AGEs/RAGE 通过 MAPK 信号通路促进大鼠内皮祖细胞向成骨细胞分化[D].泸州:西南医科大学,2017.
[42] 李运江. IL-17 对成骨细胞的影响及自噬的作用[D].福州:福建医科大学,2017.
[43] KATO S, KAWASE M, KATO D, et al.Decrease of bone mineral density in Japanese patients with non-metastatic prostate cancer treated with androgen deprivation therapy[J]. J Bone Miner Metab,2019,37(1):72-80.