Skip to content
2000
Volume 20, Issue 9
  • ISSN: 1574-8855
  • E-ISSN: 2212-3903

Abstract

Background

Danxiong Huoxue tablets has been used clinically to prevent and treat heterotopic ossification (HO) after total hip arthroplasty, but its therapeutic mechanism is not clear.

Objectives

This study investigated the potential mechanism of action of Danxiong Huoxue tablets against HO using network pharmacology and molecular docking methods.

Methods

The TCMID and SymMap databases and the existing literature were used to screen the active ingredients and targets of Danxiong Huoxue tablets, and the targets of heterotopic ossification were obtained from Gene Cards, DisGeNET, and PharmGkb databases. The PPI network diagram was constructed using the String database and Cytoscape 3.9.1 software. Finally, the core targets were analyzed by GO and KEGG enrichment and validated by molecular docking.

Results

A total of 39 active ingredients and 328 corresponding targets of Danxiong Huoxue tablets were identified, which were enriched in signaling pathways, such as PI3K/Akt and MAPK. Molecular docking verified that there was good binding activity between the core targets and the corresponding components.

Conclusion

Danxiong Huoxue tablets may prevent and treat HO by acting on key targets, such as SRC, AKT1, JUN, and TNF, and regulating the PI3K/Akt signaling pathway and MAPK signaling pathway.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdth/10.2174/0115748855341056240911101658
2024-09-27
2026-01-21

  • From This Site

    /content/journals/cdth/10.2174/0115748855341056240911101658
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SuiC. RobinsonT.E. WilliamsR.L. EisensteinN.M. GroverL.M. Triggered metabolism of adenosine triphosphate as an explanation for the chemical heterogeneity of heterotopic ossification.Commun. Chem.20236122710.1038/s42004‑023‑01015‑z37857687
     [Google Scholar]
  2. WangH. WangX. ZhangQ. LiangY. WuH. Matrine reduces traumatic heterotopic ossification in mice by inhibiting M2 macrophage polarization through the MAPK pathway.Biomed. Pharmacother.202417711713010.1016/j.biopha.2024.11713039018873
     [Google Scholar]
  3. HermanZ.J. EdelmanD.G. IlyasA.M. Heterotopic Ossification After Elbow Fractures.Orthopedics2021441101610.3928/01477447‑20201119‑0333238018
     [Google Scholar]
  4. TeasellR.W. MehtaS. AubutJ.L. AsheM.C. SequeiraK. MacalusoS. TuL. A systematic review of the therapeutic interventions for heterotopic ossification after spinal cord injury.Spinal Cord201048751252110.1038/sc.2009.17520048753
     [Google Scholar]
  5. ŁęgoszP. OtworowskiM. SibilskaA. StarszakK. KotrychD. KwapiszA. SynderM. Heterotopic Ossification: A Challenging Complication of Total Hip Arthroplasty: Risk Factors, Diagnosis, Prophylaxis, and Treatment.BioMed Res. Int.201920191810.1155/2019/386014231119167
     [Google Scholar]
  6. AgarwalS. LoderS. CholokD. LiJ. BreulerC. DrakeJ. BrownleyC. PetersonJ. LiS. LeviB. Surgical Excision of Heterotopic Ossification Leads to Re-Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence.Stem Cells Transl. Med.20176379980610.5966/sctm.2015‑036528297577
     [Google Scholar]
  7. KanS.L. YangB. NingG.Z. ChenL.X. LiY.L. GaoS.J. ChenX.Y. SunJ.C. FengS.Q. Nonsteroidal Anti-inflammatory Drugs as Prophylaxis for Heterotopic Ossification after Total Hip Arthroplasty.Medicine (Baltimore)20159418e82810.1097/MD.000000000000082825950691
     [Google Scholar]
  8. MujtabaB. TaherA. FialaM.J. NassarS. MadewellJ.E. HanafyA.K. AslamR. Heterotopic ossification: radiological and pathological review.Radiol. Oncol.201953327528410.2478/raon‑2019‑003931553710
     [Google Scholar]
  9. ZhuJ. FuH. ZhangB. GongZ. Observation on the Clinical Efficacy of Danxiong Huoxue Tablets Combined with Arthroscopic Rotator Cuff Repair for the Treatment of Rotator Cuff Injury of Qi Stagnation and Blood Stasis Type.J Guangzhou Univ Tradit Chin Med2023400922122217
     [Google Scholar]
  10. HuangZ CaiL. Effect of Living Blood Spirit Tablets on heterotopic ossification after total hip arthroplasty. Chin Arch Tradit Chin Med20022002615-6
     [Google Scholar]
  11. DuH. LiZ. SuL. HeZ. TanX. HouF. HeT. PanY. XuS. CaoL. DongS. MaY. Synthesis, characterization, and mechanistic insights into the enhanced anti-inflammatory activity of baicalin butyl ester via the PI3K-AKT pathway.Front. Pharmacol.202415141737210.3389/fphar.2024.141737239104394
     [Google Scholar]
  12. LiuB. LiuH. Experimental Research Progress of Chinese Herbal Epimedium in the Treatment of Osteoporosis.Zhongguo Zhongyiyao Xiandai Yuancheng Jiaoyu2021194194197
     [Google Scholar]
  13. WangY. FangQ. ZhengC. Research Progress of Phytochemistry, Pharmacological Action and Quality Control ofSalvia Miltiorrhiza.China Pharm20202915610
     [Google Scholar]
  14. LiQ. WuX. New progress in research on chemical constituents and pharmacological action of Ligusticum chuanxiong Hort.Chem. Eng.20203416264
     [Google Scholar]
  15. DengC. LiuS. XuX. Research Progress on Chemical Constituents and Pharmacological Effects of Sappan lignum.Zhongguo Xiandai Zhongyao2020225810826
     [Google Scholar]
  16. WangL. WangY. ZhuM. Research Progress on Active Ingredients and Pharmacological of Eupolyphaga Sinesis Walker.Chem Ind Times20173163436
     [Google Scholar]
  17. LinY. WenY. HuangH. LiF. DengY. FengJ. Research Progress on Chemical Constituents and Pharmacological Effects of Dragon’s Blood.Chinese Journal of Ethnomedicine and Ethnopharmacy20202965055
     [Google Scholar]
  18. LiY. WenY. YangX. ChenL. LiangX. YuanJ. Chemical constituents from ethyl acetate extract of Eupatorium adenophorum.Chin. Tradit. Herbal Drugs2020514932936
     [Google Scholar]
  19. MaZ. SaiS. DuoJ. Content Determination of 6 Kinds of Triterpene Acid in Tibetan Medicine Rubus biflorus by Pre-column Derivatization HPLC/FLD-APCI/MS.China Pharm2019301622432247
     [Google Scholar]
  20. KangK. ZhangJ. LiuS. LiN. Simultaneous Determination of Tetrandrine and Fangchinoline in HuamoyanTablets/Granules by Solid Phase Extraction-HPLC Method.Chinese Journal of Drug Evaluation2020373196200
     [Google Scholar]
  21. FengX. LiuZ. WangH. Extraction of active components from mulberry branches and their antibacterial and antioxidant activities.Jiangsu Agricultural Sciences2020487217221
     [Google Scholar]
  22. JiJ. YuB. Analysis of Traumatic Heterotopic Ossification from “Xigu Belongs to Bone” Theory.Clinical Journal of Traditional Chinese Medicine20243603475478
     [Google Scholar]
  23. HuM. FengY. ZhouR. Exploration on the Mechanism of Panax Notoginseng Saponins in the Treatment of Heterotopic Ossification based on Network Pharmacology and Molecular Docking.Zhongyao Xinyao Yu Linchuang Yaoli20233407948958
     [Google Scholar]
  24. ZhuW. Analysis of the Preventive Effect of Buyang Huanwu Decoction on Postoperative Heterotopic Ossification after Total Hip Arthroplasty.J Math Med2019326918920
     [Google Scholar]
  25. DeyD. WheatleyB.M. CholokD. AgarwalS. YuP.B. LeviB. DavisT.A. The traumatic bone: trauma-induced heterotopic ossification.Transl. Res.20171869511110.1016/j.trsl.2017.06.00428668522
     [Google Scholar]
  26. LiL. TuanR.S. Mechanism of traumatic heterotopic ossification: In search of injury-induced osteogenic factors.J. Cell. Mol. Med.20202419110461105510.1111/jcmm.1573532853465
     [Google Scholar]
  27. EganK.P. DuqueG. KeenanM.A. PignoloR.J. Circulating osteogentic precursor cells in non-hereditary heterotopic ossification.Bone2018109616410.1016/j.bone.2017.12.02829305336
     [Google Scholar]
  28. Felix-IlemhenbhioF. PickeringG.A.E. Kiss-TothE. WilkinsonJ.M. Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.Int. J. Mol. Sci.20222313698310.3390/ijms2313698335805978
     [Google Scholar]
  29. HuangY. WangX. LinH. The hypoxic microenvironment: a driving force for heterotopic ossification progression.Cell Commun. Signal.20201812010.1186/s12964‑020‑0509‑132028956
     [Google Scholar]
  30. ZengH. ZhanX. NiuY. Pathogenesis and progress of diagnosis and treatment of traumatic heterotopic ossification.Med J Chin People’s Armed Police Forces20223317580
     [Google Scholar]
  31. WuY.X. WuT. XuB. XuX. ChenH. LiX. WangG. Protocatechuic acid inhibits osteoclast differentiation and stimulates apoptosis in mature osteoclasts.Biomed. Pharmacother.20168239940510.1016/j.biopha.2016.05.00827470378
     [Google Scholar]
  32. Wan OsmanW.N. Che Ahmad TantowiN.A. LauS.F. MohamedS. Epicatechin and scopoletin rich Morinda citrifolia (Noni) leaf extract supplementation, mitigated Osteoarthritis via anti-inflammatory, anti-oxidative, and anti-protease pathways.J. Food Biochem.2019433e1275510.1111/jfbc.1275531353568
     [Google Scholar]
  33. WangT. LiS. YiC. WangX. HanX. Protective Role of β-Sitosterol in Glucocorticoid-Induced Osteoporosis in Rats via the RANKL/OPG Pathway.Altern. Ther. Health Med.2022287182535648689
     [Google Scholar]
  34. MatsubaraT. YasudaK. MizutaK. KawaueH. KokabuS. Tyrosine kinase src is a regulatory factor of bone homeostasis.Int. J. Mol. Sci.20222310550810.3390/ijms2310550835628319
     [Google Scholar]
  35. SchreiberC. SaraswatiS. HarkinsS. GruberA. CremersN. ThieleW. RothleyM. PlaumannD. KornC. ArmantO. AugustinH.G. SleemanJ.P. Loss of ASAP1 in mice impairs adipogenic and osteogenic differentiation of mesenchymal progenitor cells through dysregulation of FAK/Src and AKT signaling.PLoS Genet.2019156e100821610.1371/journal.pgen.100821631246957
     [Google Scholar]
  36. AlvandiZ. OpasM. c-Src kinase inhibits osteogenic differentiation via enhancing STAT1 stability.PLoS One20201511e024164610.1371/journal.pone.024164633180789
     [Google Scholar]
  37. ChenM. ShanL. GanY. TianL. ZhouJ. ZhuE. YuanH. LiX. WangB. Metastasis suppressor 1 controls osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling.Cell. Mol. Life Sci.202279210710.1007/s00018‑022‑04147‑y35094173
     [Google Scholar]
  38. MoonJ.B. KimJ.H. KimK. YounB.U. KoA. LeeS.Y. KimN. Akt induces osteoclast differentiation through regulating the GSK3β/NFATc1 signaling cascade.J. Immunol.2012188116316910.4049/jimmunol.110125422131333
     [Google Scholar]
  39. SuzukiE. Ochiai-ShinoH. AokiH. OnoderaS. SaitoA. SaitoA. AzumaT. Akt activation is required for TGF-β1-induced osteoblast differentiation of MC3T3-E1 pre-osteoblasts.PLoS One2014912e11256610.1371/journal.pone.011256625470129
     [Google Scholar]
  40. KawamuraN. KugimiyaF. OshimaY. OhbaS. IkedaT. SaitoT. ShinodaY. KawasakiY. OgataN. HoshiK. AkiyamaT. ChenW.S. HayN. TobeK. KadowakiT. AzumaY. TanakaS. NakamuraK. ChungU. KawaguchiH. Akt1 in osteoblasts and osteoclasts controls bone remodeling.PLoS One2007210e105810.1371/journal.pone.000105817957242
     [Google Scholar]
  41. KaplanF.S. ShoreE.M. Bone morphogenetic proteins and c-fos: Early signals in endochondral bone formation.Bone1996191Suppl.S13S2110.1016/S8756‑3282(96)00129‑98830995
     [Google Scholar]
  42. HwangS.G. YuS.S. LeeS.W. ChunJ.S. Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway.FEBS Lett.2005579214837484210.1016/j.febslet.2005.07.06716099458
     [Google Scholar]
  43. GuiT. WeiY. LuoL. LiJ. ZhongL. YaoL. BeierF. NelsonC.L. TsourkasA. LiuX.S. Enomoto-IwamotoM. YuF. ChengZ. QinL. Activating EGFR Signaling Attenuates Osteoarthritis Development Following Loading Injury in Mice.J. Bone Miner. Res.202037122498251110.1002/jbmr.471736178273
     [Google Scholar]
  44. QinL. BeierF. EGFR Signaling: Friend or Foe for Cartilage?JBMR Plus201932e1017710.1002/jbm4.1017730828691
     [Google Scholar]
  45. IsajiM. HoriuchiK. KondoS. NakagawaT. IshizakaT. AmakoM. ChibaK. Suppression of TNF-α activity by immobilization rescues Mkx expression and attenuates tendon ossification in a mouse Achilles tenotomy model.J. Orthop. Res.2024jor.2590610.1002/jor.2590638806292
     [Google Scholar]
  46. KitaK. KimuraT. NakamuraN. YoshikawaH. NakanoT. PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation.Genes Cells200813883985010.1111/j.1365‑2443.2008.01209.x18782222
     [Google Scholar]
  47. ZhangH. ChenX. XueP. MaX. LiJ. ZhangJ. FN1 promotes chondrocyte differentiation and collagen production via TGF-β/PI3K/Akt pathway in mice with femoral fracture.Gene202176914525310.1016/j.gene.2020.14525333098939
     [Google Scholar]
  48. McGonnellI.M. GrigoriadisA.E. LamE.W.F. PriceJ.S. SuntersA. A specific role for phosphoinositide 3-kinase and AKT in osteoblasts?Front. Endocrinol. (Lausanne)201238810.3389/fendo.2012.0008822833734
     [Google Scholar]
  49. TangL. WuM. LuS. ZhangH. ShenY. ShenC. LiangH. GeH. DingX. WangZ. Fgf9 Negatively Regulates Bone Mass by Inhibiting Osteogenesis and Promoting Osteoclastogenesis via MAPK and PI3K/AKT Signaling.J. Bone Miner. Res.202036477979110.1002/jbmr.423033316109
     [Google Scholar]
  50. DongJ. XuX. ZhangQ. YuanZ. TanB. The PI3K/AKT pathway promotes fracture healing through its crosstalk with Wnt/β-catenin.Exp. Cell Res.2020394111213710.1016/j.yexcr.2020.11213732534061
     [Google Scholar]
  51. ZhengH. LiuJ. TycksenE. NunleyR. McAlindenA. MicroRNA-181a/b-1 over-expression enhances osteogenesis by modulating PTEN/PI3K/AKT signaling and mitochondrial metabolism.Bone20191239210210.1016/j.bone.2019.03.02030898695
     [Google Scholar]
  52. ChangH.H. LinI.C. WuC.W. HungC.Y. LiuW.C. WuC.Y. ChengC.L. WuK.L.H. High fructose induced osteogenic differentiation of human valve interstitial cells via activating PI3K/AKT/mitochondria signaling.Biomed. J.202245349150310.1016/j.bj.2021.06.00834229104
     [Google Scholar]
  53. SmithC.O. EliseevR.A. Energy Metabolism During Osteogenic Differentiation: The Role of Akt.Stem Cells Dev.202130314916210.1089/scd.2020.014133307974
     [Google Scholar]
  54. ChenC. SongC. LiuB. WangY. JiaJ. PangK. WangY. WangP. Activation of BMP4/SMAD pathway by HIF-1α in hypoxic environment promotes osteogenic differentiation of BMSCs and leads to ectopic bone formation.Tissue Cell20248810237610.1016/j.tice.2024.10237638608407
     [Google Scholar]
  55. ZhangZ. YaoL. YangJ. WangZ. DuG. PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review).Mol. Med. Rep.20181843547355410.3892/mmr.2018.937530106145
     [Google Scholar]
  56. ValerJ.A. Sánchez-de-DiegoC. GámezB. MishinaY. RosaJ.L. VenturaF. Inhibition of phosphatidylinositol 3-kinase α ( PI 3Kα) prevents heterotopic ossification.EMBO Mol. Med.2019119e1056710.15252/emmm.20191056731373426
     [Google Scholar]
  57. Van AllerG.S. CarsonJ.D. TangW. PengH. ZhaoL. CopelandR.A. TumminoP.J. LuoL. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor.Biochem. Biophys. Res. Commun.2011406219419910.1016/j.bbrc.2011.02.01021300025
     [Google Scholar]
  58. ZhangJ. FuB. ChenX. ChenD. YangH. Protocatechuic acid attenuates anterior cruciate ligament transection-induced osteoarthritis by suppressing osteoclastogenesis.Exp. Ther. Med.202019123224031853294
     [Google Scholar]
  59. Sung HsiehH.H. ChungM.T. AllenR.M. RanganathanK. HabboucheJ. CholokD. ButtsJ. KauraA. Tiruvannamalai-AnnamalaiR. BreulerC. PriestC. LoderS.J. LiJ. LiS. StegemannJ. KunkelS.L. LeviB. Evaluation of salivary cytokines for diagnosis of both trauma-induced and genetic heterotopic ossification.Front. Endocrinol. (Lausanne)201787410.3389/fendo.2017.0007428484423
     [Google Scholar]
  60. ChowY.Y. ChinK.Y. The role of inflammation in the pathogenesis of osteoarthritis.Mediators Inflamm.2020202011910.1155/2020/829392132189997
     [Google Scholar]
  61. SchettG. ZwerinaJ. FiresteinG. The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis.Ann. Rheum. Dis.200867790991610.1136/ard.2007.07427817827184
     [Google Scholar]
  62. BeamerE. CorrêaS.A.L. The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission.Front. Cell Dev. Biol.2021963563610.3389/fcell.2021.63563633585492
     [Google Scholar]
  63. LiuR. HaoD. XuW. LiJ. LiX. ShenD. ShengK. ZhaoL. XuW. GaoZ. ZhaoX. LiuQ. ZhangY. β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice.Pharm. Biol.201957116116810.1080/13880209.2019.157746130905278
     [Google Scholar]
  64. RuanH. MuJ. Effect of Epicatechin on Inflammatory Cytokines in LPS-induced RAW264.7 Cell.Zhongguo Shiyan Fangjixue Zazhi2017234159163
     [Google Scholar]
  65. HeM. LiuJ. FangY. WangF. HanQ. LiuX. Research progress of Chinese medicine in treating blood stasis in osteoarthritis of the knee.Hubei Journal of Traditional Chinese Medicine20224465963
     [Google Scholar]
  66. MeiY. WeiL. ChaiC. ZouL. LiuX. ChenJ. TanM. WangC. CaiZ. ZhangF. YinS. A method to study the distribution patterns for metabolites in xylem and phloem of spatholobi caulis.Molecules201925116710.3390/molecules2501016731906156
     [Google Scholar]
  67. LendeA.B. KshirsagarA.D. DeshpandeA.D. MuleyM.M. PatilR.R. BafnaP.A. NaikS.R. Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice.Inflammopharmacology201119525526310.1007/s10787‑011‑0086‑421748471
     [Google Scholar]
  68. JalaliO BestM WongA SchaefferB BauerB JohnsonL. Protocatechuic Acid as a Topical Antimicrobial for Surgical Skin Antisepsis: Preclinical Investigations.JB JS Open Access202053e19.00079
     [Google Scholar]
  69. BettaiebA CremoniniE KangH KangJ HajFG OteizaPI Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice.Int J Biochem Cell Biol201681Pt B38392
     [Google Scholar]
  70. MonikaP. ChandraprabhaM.N. MurthyK.N.C. Catechin, epicatechin, curcumin, garlic, pomegranate peel and neem extracts of Indian origin showed enhanced anti-inflammatory potential in human primary acute and chronic wound derived fibroblasts by decreasing TGF-β and TNF-α expression.BMC Complementary Medicine and Therapies202323118110.1186/s12906‑023‑03993‑y37268940
     [Google Scholar]
  71. MorkS. JohannessenM. Škalko-BasnetN. JøraholmenM.W. Chitosan and liposomal delivery systems for epicatechin or propyl gallate targeting localized treatment of vulvovaginal candidiasis.Int. J. Pharm.202466212448910.1016/j.ijpharm.2024.12448939032871
     [Google Scholar]
  72. GogoiD. PalA. ChattopadhyayP. PaulS. DekaR.C. MukherjeeA.K. First report of plant-derived β-sitosterol with antithrombotic, in vivo anticoagulant, and thrombus-preventing activities in a mouse model.J. Nat. Prod.201881112521253010.1021/acs.jnatprod.8b0057430406661
     [Google Scholar]
  73. HuangS. HeX. HuangC. HeW. ZhaoH. DaiJ. XuG. Thrombin-targeted screening of anticoagulant active components from Polygonum amplexicaule D. Don var. sinense Forb by affinity ultrafiltration coupled with UPLC-Q-TOF-MS.Phytochem. Anal.20243551112112210.1002/pca.334638500381
     [Google Scholar]
  74. FuY. JiaY. SunY. LiuX. YiJ. CaiS. Dietary flavonoids alleviate inflammation and vascular endothelial barrier dysfunction induced by advanced glycation end products in vitro.Nutrients2022145102610.3390/nu1405102635268006
     [Google Scholar]
  75. HalderS.K. AhmadI. ShathiJ.F. MimM.M. HassanM.R. JewelM.J.I. DeyP. IslamM.S. PatelH. MorshedM.R. ShakilM.S. HossenM.S. A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an in silico structure-based drug discovery.Mol. Biotechnol.202466461262510.1007/s12033‑022‑00582‑136307631
     [Google Scholar]
/content/journals/cdth/10.2174/0115748855341056240911101658
Loading
Network Pharmacology and Molecular Docking to Explore the Mechanism of Action of Danxiong Huoxue Tablets for the Prevention and Treatment of Heterotopic Ossification
Curr Drug Ther 20, 1288 (2025); https://doi.org/10.2174/0115748855341056240911101658
/content/journals/cdth/10.2174/0115748855341056240911101658
/content/journals/cdth/10.2174/0115748855341056240911101658
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Danxiong Huoxue tablets; heterotopic ossification; mechanism database; molecular docking; network pharmacology

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test