Mechanistic Insights into the Anti-Osteoporotic Effects of Naringin via Network Pharmacology and Molecular Docking Studies

Xiaodong Li; Xin Qi; Yincang Wang; Xinyue Yang; Xiangyu Cui; Dawang Wang; Boyuan Kang; Xiaofeng Zhang*; Xilin Xu*

Xiaodong Li, Xin Qi, Yincang Wang, Xinyue Yang, Xiangyu Cui, Dawang Wang, Boyuan Kang, Xiaofeng Zhang* and Xilin Xu*

Volume5-Issue8
Dates: Received: 2024-07-30 | Accepted: 2024-08-04 | Published: 2024-08-05
Pages: 880-895

Abstract

Background: Naringin, a natural flavonoid prevalent in citrus fruits, is known for its antioxidant, anti-inflammatory, and antitumor properties. Recent studies suggest its potential influence on bone metabolism, proposing it as an anti-osteoporotic agent. However, specific mechanisms of action remain unclear.
Objective: This study aimed to validate the anti-osteoporotic effects of naringin by combining network pharmacology analysis and molecular docking validation.

Methods: Employing network pharmacology and molecular docking, we constructed an analysis framework for "Naringin-Targets-GO and KEGG-Osteoporosis" using Cytoscape software and R software. This framework integrated various online public databases, Protein-Protein Interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking using AutoDock Vina software.

Results: We identified 272 target genes associated with naringin and 5,785 target genes related to osteoporosis, with 197 overlapping genes. Further analysis led to the selection of eight core targets: TP53, TNF, JUN, STAT3, AKT1, ESR1, BCL2, and IL6. GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that naringin might influence osteoporosis progression by regulating biological processes, such as apoptosis, cell proliferation, and inflammatory responses, as well as signaling pathways, such as TNF, FoxO, and PI3K-Akt. Molecular docking validation confirmed the high binding affinity of naringin to the eight core targets, with binding energies below 7.2 kcal/mol.

Conclusion: The therapeutic mechanism of naringin against osteoporosis may involve the regulation of gene expression, including TP53, IL6, TNF, JUN, STAT3, AKT1, ESR1, and BCL2, and mediating signaling pathways such as TNF, FoxO, IL-17, PI3K-Akt, AMPK, and VEGF, thereby affecting multiple biological processes, such as bidirectional regulation of osteoblast proliferation and apoptosis, angiogenesis, and downregulation of inflammatory responses.

FullText HTML FullText PDF DOI: 10.37871/jbres1967

Certificate of Publication

Copyright

How to cite this article

Li X, Qi X, Wang Y, Yang X, Cui X, Wang D, Kang B, Zhang X, Xu X. Mechanistic Insights into the Anti-Osteoporotic Effects of Naringin via Network Pharmacology and Molecular Docking Studies. J Biomed Res Environ Sci. 2024 Aug 05; 5(8): 880-895. doi: 10.37871/jbres1967, Article ID: JBRES1967, Available at: https://www.jelsciences.com/articles/jbres1967.pdf

Subject area(s)

Orthopedics

Pharmacology

References

Gregson CL, Armstrong DJ, Bowden J, Cooper C, Edwards J, Gittoes NJL, Harvey N, Kanis J, Leyland S, Low R, McCloskey E, Moss K, Parker J, Paskins Z, Poole K, Reid DM, Stone M, Thomson J, Vine N, Compston J. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2022 Apr 5;17(1):58. doi: 10.1007/s11657-022-01061-5. Erratum in: Arch Osteoporos. 2022 May 19;17(1):80. doi: 10.1007/s11657-022-01115-8. PMID: 35378630; PMCID: PMC8979902.
Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019 Jan 26;393(10169):364-376. doi: 10.1016/S0140-6736(18)32112-3. PMID: 30696576.
Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 2017 Nov;5(11):898-907. doi: 10.1016/S2213-8587(17)30188-2. Epub 2017 Jul 7. PMID: 28689769; PMCID: PMC5798872.
Adamczak A, Ożarowski M, Karpiński TM. Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants. J Clin Med. 2019 Dec 31;9(1):109. doi: 10.3390/jcm9010109. PMID: 31906141; PMCID: PMC7019947.
Zhang F, Huang X, Qi Y, Qian Z, Ni S, Zhong Z, Zhang X, Li D, Yu B. Juglanin Inhibits Osteoclastogenesis in Ovariectomized Mice via the Suppression of NF-κB Signaling Pathways. Front Pharmacol. 2021 Jan 27;11:596230. doi: 10.3389/fphar.2020.596230. PMID: 33708115; PMCID: PMC7941268.
Ge X, Zhou G. Protective effects of naringin on glucocorticoid-induced osteoporosis through regulating the PI3K/Akt/mTOR signaling pathway. Am J Transl Res. 2021 Jun 15;13(6):6330-6341. PMID: 34306372; PMCID: PMC8290725.
Cao X, Lin W, Liang C, Zhang D, Yang F, Zhang Y, Zhang X, Feng J, Chen C. Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway. Immunol Res. 2015 Jul;62(3):357-67. doi: 10.1007/s12026-015-8665-x. PMID: 26032685.
Ma X, Lv J, Sun X, Ma J, Xing G, Wang Y, Sun L, Wang J, Li F, Li Y, Zhao Z. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone. Sci Rep. 2016 Apr 25;6:24562. doi: 10.1038/srep24562. PMID: 27109829; PMCID: PMC4842995.
Cao G, Hu S, Ning Y, Dou X, Ding C, Wang L, Wang Z, Sang X, Yang Q, Shi J, Hao M, Han X. Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity. Front Pharmacol. 2024 Apr 2;15:1370900. doi: 10.3389/fphar.2024.1370900. PMID: 38628648; PMCID: PMC11019011.
Wang F, Rong P, Wang J, Yu X, Wang N, Wang S, Xue Z, Chen J, Meng W, Peng X. Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation. Food Funct. 2022 Jun 6;13(11):6419-6432. doi: 10.1039/d2fo00952h. PMID: 35616518.
Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014 Apr 16;6:13. doi: 10.1186/1758-2946-6-13. PMID: 24735618; PMCID: PMC4001360..
Davis AP, Grondin CJ, Johnson RJ, Sciaky D, Wiegers J, Wiegers TC, Mattingly CJ. Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Res. 2021 Jan 8;49(D1):D1138-D1143. doi: 10.1093/nar/gkaa891. PMID: 33068428; PMCID: PMC7779006.
Kim S. Getting the most out of PubChem for virtual screening. Expert Opin Drug Discov. 2016 Sep;11(9):843-55. doi: 10.1080/17460441.2016.1216967. Epub 2016 Aug 5. PMID: 27454129; PMCID: PMC5045798.
Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019 Jul 2;47(W1):W357-W364. doi: 10.1093/nar/gkz382. PMID: 31106366; PMCID: PMC6602486.
Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Gable AL, Fang T, Doncheva NT, Pyysalo S, Bork P, Jensen LJ, von Mering C. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. doi: 10.1093/nar/gkac1000. PMID: 36370105; PMCID: PMC9825434.
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016 Jun 20;54:1.30.1-1.30.33. doi: 10.1002/cpbi.5. PMID: 27322403.
Piñero J, Ramírez-Anguita JM, Saüch-Pitarch J, Ronzano F, Centeno E, Sanz F, Furlong LI. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 2020 Jan 8;48(D1):D845-D855. doi: 10.1093/nar/gkz1021. PMID: 31680165; PMCID: PMC7145631.
Bardou P, Mariette J, Escudié F, Djemiel C, Klopp C. jvenn: an interactive Venn diagram viewer. BMC Bioinformatics. 2014 Aug 29;15(1):293. doi: 10.1186/1471-2105-15-293. PMID: 25176396; PMCID: PMC4261873.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 Nov;13(11):2498-504. doi: 10.1101/gr.1239303. PMID: 14597658; PMCID: PMC403769.
Momota R, Ohtsuka A. Network of anatomical texts (NAnaTex), an open-source project for visualizing the interaction between anatomical terms. Anat Sci Int. 2018 Jan;93(1):149-153. doi: 10.1007/s12565-017-0410-1. Epub 2017 Jul 24. PMID: 28741222.
Ariel de Lima D, Helito CP, de Lima LL, Clazzer R, Gonçalves RK, de Camargo OP. HOW TO PERFORM A META-ANALYSIS: A PRACTICAL STEP-BY-STEP GUIDE USING R SOFTWARE AND RSTUDIO. Acta Ortop Bras. 2022 May 23;30(3):e248775. doi: 10.1590/1413-785220223003e248775. PMID: 35694025; PMCID: PMC9150877.
Tang Y, Li M, Wang J, Pan Y, Wu FX. CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems. 2015 Jan;127:67-72. doi: 10.1016/j.biosystems.2014.11.005. Epub 2014 Nov 15. PMID: 25451770.
Hu Y, Yuan W, Cai N, Jia K, Meng Y, Wang F, Ge Y, Lu H. Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models. Life (Basel). 2022 Jun 29;12(7):980. doi: 10.3390/life12070980. PMID: 35888070; PMCID: PMC9322149.
Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(5):P3. Epub 2003 Apr 3. PMID: 12734009.
Morris GM, Huey R, Olson AJ. Using AutoDock for ligand-receptor docking. Curr Protoc Bioinformatics. 2008 Dec;Chapter 8:Unit 8.14. doi: 10.1002/0471250953.bi0814s24. PMID: 19085980.
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235. PMID: 10592235; PMCID: PMC102472.
Paquet E, Viktor HL. Macromolecular structure comparison and docking: an algorithmic review. Curr Pharm Des. 2013;19(12):2183-93. doi: 10.2174/1381612811319120006. PMID: 23016846.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan 30;31(2):455-61. doi: 10.1002/jcc.21334. PMID: 19499576; PMCID: PMC3041641.
Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 2010 May;24(5):417-22. doi: 10.1007/s10822-010-9352-6. Epub 2010 Apr 17. PMID: 20401516; PMCID: PMC2881210.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023 Jan 6;51(D1):D587-D592. doi: 10.1093/nar/gkac963. PMID: 36300620; PMCID: PMC9825424.
Gan J, Deng X, Le Y, Lai J, Liao X. The Development of Naringin for Use against Bone and Cartilage Disorders. Molecules. 2023 Apr 25;28(9):3716. doi: 10.3390/molecules28093716. PMID: 37175126; PMCID: PMC10180405.
Lodewyckx L, Lories RJ. WNT Signaling in osteoarthritis and osteoporosis: what is the biological significance for the clinician? Curr Rheumatol Rep. 2009 Feb;11(1):23-30. doi: 10.1007/s11926-009-0004-6. PMID: 19171108.
Jiang Q, Li WQ, Aiello FB, Mazzucchelli R, Asefa B, Khaled AR, Durum SK. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 2005 Aug-Oct;16(4-5):513-33. doi: 10.1016/j.cytogfr.2005.05.004. PMID: 15996891.
Callil-Soares PH, Biasi LCK, Pessoa Filho PA. Effect of preprocessing and simulation parameters on the performance of molecular docking studies. J Mol Model. 2023 Jul 15;29(8):251. doi: 10.1007/s00894-023-05637-x. PMID: 37452150.
Chinnamadhu A, Ramakrishnan J, Suresh S, Ramadurai P, Poomani K. Dynamics and binding affinity of nucleoside and non-nucleoside inhibitors with RdRp of SARS-CoV-2: a molecular screening, docking, and molecular dynamics simulation study. J Biomol Struct Dyn. 2023 Dec;41(20):10396-10410. doi: 10.1080/07391102.2022.2154844. Epub 2022 Dec 12. PMID: 36510678.
Rosignoli S, Paiardini A. Boosting the Full Potential of PyMOL with Structural Biology Plugins. Biomolecules. 2022 Nov 27;12(12):1764. doi: 10.3390/biom12121764. PMID: 36551192; PMCID: PMC9775141.
Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013 Mar;27(3):221-34. doi: 10.1007/s10822-013-9644-8. Epub 2013 Apr 12. PMID: 23579614.
Kumar S, Nussinov R. Salt bridge stability in monomeric proteins. J Mol Biol. 1999 Nov 12;293(5):1241-55. doi: 10.1006/jmbi.1999.3218. PMID: 10547298.
Chandler D. Interfaces and the driving force of hydrophobic assembly. Nature. 2005 Sep 29;437(7059):640-7. doi: 10.1038/nature04162. PMID: 16193038.
Bornhof AB, Bauzá A, Aster A, Pupier M, Frontera A, Vauthey E, Sakai N, Matile S. Synergistic Anion-(π) n-π Catalysis on π-Stacked Foldamers. J Am Chem Soc. 2018 Apr 11;140(14):4884-4892. doi: 10.1021/jacs.8b00809. Epub 2018 Apr 2. PMID: 29608309.
LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-2102. doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28. Erratum in: Osteoporos Int. 2022 Oct;33(10):2243. doi: 10.1007/s00198-022-06479-8. PMID: 35478046; PMCID: PMC9546973.
Li J, Fu SF, Yang Y, An R, Liu HY, Mao HP. Clinical practice of traditional Chinese medicine for the treatment of postmenopausal osteoporosis: a literature review. Climacteric. 2022 Dec;25(6):562-569. doi: 10.1080/13697137.2022.2102894. Epub 2022 Aug 2. PMID: 35916317.
Zeng X, Zheng Y, He Y, Zhang J, Peng W, Su W. Microbial Metabolism of Naringin and the Impact on Antioxidant Capacity. Nutrients. 2022 Sep 13;14(18):3765. doi: 10.3390/nu14183765. PMID: 36145140; PMCID: PMC9502552.
Yu KE, Alder KD, Morris MT, Munger AM, Lee I, Cahill SV, Kwon HK, Back J, Lee FY. Re-appraising the potential of naringin for natural, novel orthopedic biotherapies. Ther Adv Musculoskelet Dis. 2020 Dec 8;12:1759720X20966135. doi: 10.1177/1759720X20966135. PMID: 33343723; PMCID: PMC7727086.
Bharti S, Rani N, Krishnamurthy B, Arya DS. Preclinical evidence for the pharmacological actions of naringin: a review. Planta Med. 2014 Apr;80(6):437-51. doi: 10.1055/s-0034-1368351. Epub 2014 Apr 7. PMID: 24710903.
Gan J, Deng X, Le Y, Lai J, Liao X. The Development of Naringin for Use against Bone and Cartilage Disorders. Molecules. 2023 Apr 25;28(9):3716. doi: 10.3390/molecules28093716. PMID: 37175126; PMCID: PMC10180405.
Yu X, Shen G, Shang Q, Zhang Z, Zhao W, Zhang P, Liang D, Ren H, Jiang X. A Naringin-loaded gelatin-microsphere/nano-hydroxyapatite/silk fibroin composite scaffold promoted healing of critical-size vertebral defects in ovariectomised rat. Int J Biol Macromol. 2021 Dec 15;193(Pt A):510-518. doi: 10.1016/j.ijbiomac.2021.10.036. Epub 2021 Oct 25. PMID: 34710477.
Iantomasi T, Romagnoli C, Palmini G, Donati S, Falsetti I, Miglietta F, Aurilia C, Marini F, Giusti F, Brandi ML. Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs. Int J Mol Sci. 2023 Feb 14;24(4):3772. doi: 10.3390/ijms24043772. PMID: 36835184; PMCID: PMC9963528.
McLean RR. Proinflammatory cytokines and osteoporosis. Curr Osteoporos Rep. 2009 Dec;7(4):134-9. doi: 10.1007/s11914-009-0023-2. PMID: 19968917.
Ang ES, Yang X, Chen H, Liu Q, Zheng MH, Xu J. Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-κB and ERK activation. FEBS Lett. 2011 Sep 2;585(17):2755-62. doi: 10.1016/j.febslet.2011.07.046. Epub 2011 Aug 6. PMID: 21835177.
Tanaka Y, Nakayamada S, Okada Y. Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):325-8. doi: 10.2174/1568010054022015. PMID: 16101541.
Han Y, Gao H, Gan X, Liu J, Bao C, He C. Roles of IL-11 in the regulation of bone metabolism. Front Endocrinol (Lausanne). 2024 Jan 30;14:1290130. doi: 10.3389/fendo.2023.1290130. PMID: 38352248; PMCID: PMC10862480.
Fischer V, Haffner-Luntzer M. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Semin Cell Dev Biol. 2022 Mar;123:14-21. doi: 10.1016/j.semcdb.2021.05.014. Epub 2021 May 20. PMID: 34024716.
Jung YY, Kim C, Shanmugam MK, Deivasigamani A, Chinnathambi A, Alharbi SA, Rangappa KS, Hui KM, Sethi G, Mohan CD, Ahn KS. Leonurine ameliorates the STAT3 pathway through the upregulation of SHP-1 to retard the growth of hepatocellular carcinoma cells. Cell Signal. 2024 Feb;114:111003. doi: 10.1016/j.cellsig.2023.111003. Epub 2023 Dec 2. PMID: 38048857.
Wang W, Mao J, Chen Y, Zuo J, Chen L, Li Y, Gao Y, Lu Q. Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling. Clin Exp Pharmacol Physiol. 2022 Jan;49(1):113-121. doi: 10.1111/1440-1681.13591. Epub 2021 Oct 21. PMID: 34525226.
Rhee J, Park SH, Kim SK, Kim JH, Ha CW, Chun CH, Chun JS. Inhibition of BATF/JUN transcriptional activity protects against osteoarthritic cartilage destruction. Ann Rheum Dis. 2017 Feb;76(2):427-434. doi: 10.1136/annrheumdis-2015-208953. Epub 2016 May 4. PMID: 27147707; PMCID: PMC5284350.
Zhang Y, Liang J, Liu P, Wang Q, Liu L, Zhao H. The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies. Front Endocrinol (Lausanne). 2022 Dec 16;13:1063815. doi: 10.3389/fendo.2022.1063815. PMID: 36589815; PMCID: PMC9800780.
Pavalko FM, Gerard RL, Ponik SM, Gallagher PJ, Jin Y, Norvell SM. Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3. J Cell Physiol. 2003 Feb;194(2):194-205. doi: 10.1002/jcp.10221. PMID: 12494458.
Zhang H, Zhou C, Zhang Z, Yao S, Bian Y, Fu F, Luo H, Li Y, Yan S, Ge Y, Chen Y, Zhan K, Yue M, Du W, Tian K, Jin H, Li X, Tong P, Ruan H, Wu C. Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis. Front Endocrinol (Lausanne). 2022 Jan 28;12:841668. doi: 10.3389/fendo.2021.841668. PMID: 35154014; PMCID: PMC8831245.
Chokalingam K, Roforth MM, Nicks KM, McGregor U, Fraser D, Khosla S, Monroe DG. Examination of ERα signaling pathways in bone of mutant mouse models reveals the importance of ERE-dependent signaling. Endocrinology. 2012 Nov;153(11):5325-33. doi: 10.1210/en.2012-1721. Epub 2012 Sep 26. PMID: 23015293; PMCID: PMC3473212.
Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell. 2007 Sep 7;130(5):811-23. doi: 10.1016/j.cell.2007.07.025. PMID: 17803905.
Scheffler JM, Gustafsson KL, Barrett A, Corciulo C, Drevinge C, Del Carpio Pons AM, Humeniuk P, Engdahl C, Gustafsson JÅ, Ohlsson C, Carlsten H, Lagerquist MK, Islander U. ERα Signaling in a Subset of CXCL12-Abundant Reticular Cells Regulates Trabecular Bone in Mice. JBMR Plus. 2022 Jun 17;6(8):e10657. doi: 10.1002/jbm4.10657. PMID: 35991530; PMCID: PMC9382863.
Newton K, Strasser A, Kayagaki N, Dixit VM. Cell death. Cell. 2024 Jan 18;187(2):235-256. doi: 10.1016/j.cell.2023.11.044. PMID: 38242081.
Wang T, Peng W, Zhang F, Zheng Y, Wang Z, Yuan D. [Effects of nicotinamide mononucleotide adenylyl transferase 3 on mitochondrial function and anti-oxidative stress of rabbit bone marrow mesenchymal stem cells via regulating nicotinamide adenine dinucleotide levels]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2020 May 15;34(5):621-629. Chinese. doi: 10.7507/1002-1892.201910037. PMID: 32410431; PMCID: PMC8171852.
Yu GY, Zheng GZ, Chang B, Hu QX, Lin FX, Liu DZ, Wu CC, Du SX, Li XD. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway. Stem Cells Int. 2016;2016:7130653. doi: 10.1155/2016/7130653. Epub 2016 Mar 16. PMID: 27069482; PMCID: PMC4812486.
Wang L, Zhang YG, Wang XM, Ma LF, Zhang YM. Naringin protects human adipose-derived mesenchymal stem cells against hydrogen peroxide-induced inhibition of osteogenic differentiation. Chem Biol Interact. 2015 Dec 5;242:255-61. doi: 10.1016/j.cbi.2015.10.010. Epub 2015 Oct 19. PMID: 26482937.
Jiang Y, Luo W, Wang B, Wang X, Gong P, Xiong Y. Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life Sci. 2020 Apr 1;246:117422. doi: 10.1016/j.lfs.2020.117422. Epub 2020 Feb 11. PMID: 32057903.
Zhao J, Lin F, Liang G, Han Y, Xu N, Pan J, Luo M, Yang W, Zeng L. Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking. Front Endocrinol (Lausanne). 2022 Jan 5;12:815891. doi: 10.3389/fendo.2021.815891. PMID: 35069454; PMCID: PMC8766719.
Zha L, He L, Liang Y, Qin H, Yu B, Chang L, Xue L. TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation. Biomed Pharmacother. 2018 Jun;102:369-374. doi: 10.1016/j.biopha.2018.03.080. Epub 2018 Mar 22. PMID: 29571022.
Yao H, Yao Z, Zhang S, Zhang W, Zhou W. Upregulation of SIRT1 inhibits H2O2‑induced osteoblast apoptosis via FoxO1/β‑catenin pathway. Mol Med Rep. 2018 May;17(5):6681-6690. doi: 10.3892/mmr.2018.8657. Epub 2018 Mar 1. PMID: 29512706.
Rong Chan, Liao Liya, Lin Daojian. Naringin attenuates dexamethasone-induced apoptosis in MC3T3-E1 cells via regulation of mitochondrial apoptotic pathway. Journal of Clinical and Experimental Medicine. 2017;16(05):417-420.
Li Y, Su J, Sun W, Cai L, Deng Z. AMP-activated protein kinase stimulates osteoblast differentiation and mineralization through autophagy induction. Int J Mol Med. 2018 May;41(5):2535-2544. doi: 10.3892/ijmm.2018.3498. Epub 2018 Feb 16. PMID: 29484369; PMCID: PMC5846672.
Kanazawa I, Takeno A, Tanaka KI, Notsu M, Sugimoto T. Osteoblast AMP-Activated Protein Kinase Regulates Postnatal Skeletal Development in Male Mice. Endocrinology. 2018 Feb 1;159(2):597-608. doi: 10.1210/en.2017-00357. PMID: 29126229.
Kline J, Lee W, Wofford K. INTRAPEC Technique Controls Pectoralis Spasm and Pain for Subpectoral Breast Implantation: A Retrospective Study. Plast Reconstr Surg Glob Open. 2020 Feb 26;8(2):e2646. doi: 10.1097/GOX.0000000000002646. PMID: 32309091; PMCID: PMC7159948.
Shangguan WJ, Zhang YH, Li ZC, Tang LM, Shao J, Li H. Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. Int J Mol Med. 2017 Dec;40(6):1741-1749. doi: 10.3892/ijmm.2017.3160. Epub 2017 Sep 28. PMID: 29039439; PMCID: PMC5716435.