Skip to content
2000
image of Potential Mechanism of Gumibao Decoction in Treating Glucocorticoid-induced Osteoporosis Based on Network Pharmacology and Experimental Verification

Abstract

Objective

Gumibao decoction, a traditional Chinese herbal prescription, has demonstrated promising effects in treating osteoporosis; however, the underlying mechanism remains unclear. We investigated the regulatory mechanisms of Gumibao decoction in osteoporosis through network pharmacology analysis and validated its therapeutic effects using animal experiments.

Methods

The TCMSP database was used to screen the bioactive constituents of Gumibao decoction and identify their associated targets. Disease targets for osteoporosis were acquired through the GeneCards, PharmGKB, DrugBank, OMIM, and TTD databases. A Protein–Protein Interaction (PPI) network was generated. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were subsequently performed for the core targets identified in the PPI network. Moreover, a glucocorticoid-induced osteoporosis model was established in Sprague–Dawley (SD) rats by administering methylprednisolone and dexamethasone, and the regulatory effects of Gumibao decoction on osteoporosis were evaluated using bone mass detection and western blotting.

Results

The network pharmacology analysis identified quercetin, (−)-Epigallocatechin-3-Gallate (EGCG), kaempferol, luteolin, and fisetin as the primary bioactive components of Gumibao decoction. Core target proteins included AKT1, TP53, JUN, CTNNB1, and IL1B. The KEGG pathway enrichment analysis revealed the significant involvement of the TGF-β signalling pathway, osteoclast differentiation, and the MAPK signalling pathway in mediating its anti-osteoporotic effects. validation demonstrated that Gumibao decoction significantly ameliorated glucocorticoid-induced reductions in Bone Mineral Density (BMD) and deterioration of bone microstructure. Furthermore, protein expression analysis revealed significantly reduced levels of Smad4, phospho-Smad2/3, and TGF-β1 in the model group compared with the blank control group. Notably, all Gumibao decoction treatment groups exhibited significant upregulation of Smad4, P-Smad2/3, and TGF-β1 expression compared with the model group, validating the network pharmacology predictions implicating the TGF-β pathway.

Discussion

Research on the components of Gumibao decoction has shown that it can regulate homeostasis between osteoblasts and osteoclasts through multiple targeted pathways, thereby positively modulating bone density, bone microstructure, and bone markers. This ultimately inhibits osteoclast differentiation and stimulates osteoblast proliferation, effectively alleviating and preventing osteoporosis.

Conclusion

Gumibao decoction effectively improves glucocorticoid-induced osteoporosis, potentially by upregulating the expression of TGF-β1, P-Smad2/3, and Smad4 through the TGF-Β/Smad pathway, promoting bone formation, and restoring bone metabolic balance in glucocorticoid-induced osteoporosis rats.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073388008251008041439
2026-01-08
2026-01-30

  • From This Site

    /content/journals/cchts/10.2174/0113862073388008251008041439
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Wang D. Chen Y. Huang J. Zhang Y. Sun C. Shen Y. Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma. Biocell 2023 47 2 329 338 10.32604/biocell.2023.023489 36570878
    [Google Scholar]
  2. Auger J.P. Zimmermann M. Faas M. Stifel U. Chambers D. Krishnacoumar B. Taudte R.V. Grund C. Erdmann G. Scholtysek C. Uderhardt S. Ben Brahim O. Pascual Maté M. Stoll C. Böttcher M. Palumbo-Zerr K. Mangan M.S.J. Dzamukova M. Kieler M. Hofmann M. Blüml S. Schabbauer G. Mougiakakos D. Sonnewald U. Hartmann F. Simon D. Kleyer A. Grüneboom A. Finotto S. Latz E. Hofmann J. Schett G. Tuckermann J. Krönke G. Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids. Nature 2024 629 8010 184 192 10.1038/s41586‑024‑07282‑7 38600378
    [Google Scholar]
  3. Zhang L. Li X. Ying T. Wang T. Fu F. The use of herbal medicines for the prevention of glucocorticoid-induced osteoporosis. Front. Endocrinol. 2021 12 744647 10.3389/fendo.2021.744647 34867788
    [Google Scholar]
  4. Chen C.L. Wang J.Y. Superiority of denosumab over bisphosphonates in preventing and treating glucocorticoid-induced osteoporosis: A systematic review and meta-analysis with GRADE quality assessment. Front. Endocrinol. 2024 15 1407692 10.3389/fendo.2024.1407692 39744180
    [Google Scholar]
  5. Humphrey M.B. Russell L. Danila M.I. Fink H.A. Guyatt G. Cannon M. Caplan L. Gore S. Grossman J. Hansen K.E. Lane N.E. Ma N.S. Magrey M. McAlindon T. Robinson A.B. Saha S. Womack C. Abdulhadi B. Charles J.F. Cheah J.T.L. Chou S. Goyal I. Haseltine K. Jackson L. Mirza R. Moledina I. Punni E. Rinden T. Turgunbaev M. Wysham K. Turner A.S. Uhl S. 2022 American college of rheumatology guideline for the prevention and treatment of Glucocorticoid-Induced osteoporosis. Arthritis Rheumatol. 2023 75 12 2088 2102 10.1002/art.42646 37845798
    [Google Scholar]
  6. Wang J. Xue J.S. Huang S.M. Recent advancements in prevention and treatment of osteoporosis with traditional Chinese medicine: A long way from lab bench to bedside. Curr. Mol. Pharmacol. 2023 16 3 321 330 10.2174/1874467215666220414145641 35431007
    [Google Scholar]
  7. Wong S.K. Chin K.Y. Ima-Nirwana S. Quercetin as an agent for protecting the bone: A review of the current evidence. Int. J. Mol. Sci. 2020 21 17 6448 10.3390/ijms21176448 32899435
    [Google Scholar]
  8. Huang Y.Y. Wang Z.H. Deng L.H. Wang H. Zheng Q. Oral administration of quercetin or its derivatives inhibit bone loss in animal model of osteoporosis. Oxid. Med. Cell. Longev. 2020 2020 1 21 10.1155/2020/6080597 33194005
    [Google Scholar]
  9. Xi J. Li Q. Luo X. Li J. Guo L. Xue H. Wu G. Epigallocatechin 3 gallate protects against secondary osteoporosis in a mouse model via the Wnt/β catenin signaling pathway. Mol. Med. Rep. 2018 18 5 4555 4562 10.3892/mmr.2018.9437 30221714
    [Google Scholar]
  10. Chen S.T. Kang L. Wang C.Z. Huang P.J. Huang H.T. Lin S.Y. Chou S.H. Lu C.C. Shen P.C. Lin Y.S. Chen C.H. (−)-Epigallocatechin-3-gallate decreases osteoclastogenesis via modulation of RANKL and osteoprotegrin. Molecules 2019 24 1 156 10.3390/molecules24010156 30609798
    [Google Scholar]
  11. Wong S.K. Chin K.Y. Ima-Nirwana S. The osteoprotective effects of kaempferol: The evidence from in vivo and in vitro studies. Drug Des. Devel. Ther. 2019 13 3497 3514 10.2147/DDDT.S227738 31631974
    [Google Scholar]
  12. Sharma A.R. Nam J.S. Kaempferol stimulates WNT/β-catenin signaling pathway to induce differentiation of osteoblasts. J. Nutr. Biochem. 2019 74 108228 10.1016/j.jnutbio.2019.108228 31678747
    [Google Scholar]
  13. Adhikary S. Choudhary D. Ahmad N. Karvande A. Kumar A. Banala V.T. Mishra P.R. Trivedi R. Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival. Nutrition 2018 53 64 76 10.1016/j.nut.2017.12.003 29655780
    [Google Scholar]
  14. Jing Z. Wang C. Yang Q. Wei X. Jin Y. Meng Q. Liu Q. Liu Z. Ma X. Liu K. Sun H. Liu M. Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3β signaling pathway in vivo and in vitro. J. Cell. Physiol. 2019 234 4 4472 4490 10.1002/jcp.27252 30192012
    [Google Scholar]
  15. Zheng L. Luteolin stimulates proliferation and inhibits late differentiation of primary rat calvarial osteoblast induced by high-dose dexamethasone via Sema3A/NRP1/Pleixin A1. Curr. Pharm. Biotechnol. 2021 22 11 1538 1545 10.2174/1389201021666201216150442 33327910
    [Google Scholar]
  16. Molagoda I.M.N. Kang C-H. Lee M-H. Choi Y.H. Lee C-M. Lee S. Kim G-Y. Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation, inhibiting osteoporosis. Biochem. Pharmacol. 2021 192 114676 10.1016/j.bcp.2021.114676 34256044
    [Google Scholar]
  17. Zhang Y. Wang N. Ma J. Chen X.C. Li Z. Zhao W. Expression profile analysis of new candidate genes for the therapy of primary osteoporosis. Eur. Rev. Med. Pharmacol. Sci. 2016 20 3 433 440 26914116
    [Google Scholar]
  18. Mukherjee A. Rotwein P. Selective signaling by Akt1 controls osteoblast differentiation and osteoblast-mediated osteoclast development. Mol. Cell. Biol. 2012 32 2 490 500 10.1128/MCB.06361‑11 22064480
    [Google Scholar]
  19. Hasan L.K. Aljabban J. Rohr M. Mukhtar M. Adapa N. Salim R. Aljabban N. Syed S. Syed S. Panahiazar M. Hadley D. Jarjour W. Metaanalysis reveals genetic correlates of osteoporosis pathogenesis. J. Rheumatol. 2021 48 6 940 945 10.3899/jrheum.200951 33262303
    [Google Scholar]
  20. Wang Y. Lu L. Niu Y. Zhang Q. Cheng C. Huang H. Huang X. Huang Q. The osteoporosis risk variant rs9820407 at 3p22.1 acts as an allele-specific enhancer to regulate CTNNB1 expression by long-range chromatin loop formation. Bone 2021 153 116165 10.1016/j.bone.2021.116165 34461284
    [Google Scholar]
  21. Yu T. You X. Zhou H. Kang A. He W. Li Z. Li B. Xia J. Zhu H. Zhao Y. Yu G. Xiong Y. Yang Y. p53 plays a central role in the development of osteoporosis. Aging 2020 12 11 10473 10487 10.18632/aging.103271 32484789
    [Google Scholar]
  22. Lerbs T. Cui L. Muscat C. Saleem A. van Neste C. Domizi P. Chan C. Wernig G. Expansion of bone precursors through jun as a novel treatment for osteoporosis-associated fractures. Stem Cell Reports 2020 14 4 603 613 10.1016/j.stemcr.2020.02.009 32197115
    [Google Scholar]
  23. He Z. Sun Y. Wu J. Xiong Z. Zhang S. Liu J. Liu Y. Li H. Jin T. Yang Y. Yang S. Evaluation of genetic variants in IL‐1B and its interaction with the predisposition of osteoporosis in the northwestern Chinese Han population. J. Gene Med. 2020 22 10 3214 10.1002/jgm.3214 32391643
    [Google Scholar]
  24. Dong Y.P. Deng Y.H. Zhang T. Role of TGF-β, BMP-2, VEGF, and PDGF in fracture healing. Chin J. Clin. Basic Res. Orthop. 2024 14 03 218 225
    [Google Scholar]
  25. Xiao P. Hou P. Lin Z.J. Effects of Yinyanghuo (Epimedium), Dangui (Angelica Sinensis) and their combination drugs on TGF-β1/Smads signaling pathway in rats of postmenopausal osteoporosis. Zhongguo Guzhi Shusong Zazhi 2022 28 06 818 824
    [Google Scholar]
  26. Yuntao W. Qixin Z. Xiaodong G. Yongchao W. Jie H. Influence of exogenous TGFβ1 on the expression of Smad2 and Smad3 in rat bone marrow-derived mesenchymal stem cells. Curr. Med. Sci. 2005 25 1 68 71 10.1007/BF02831390 15934312
    [Google Scholar]
  27. Zhou Y. Gao Y. Xu C. Shen H. Tian Q. Deng H.W. A novel approach for correction of crosstalk effects in pathway analysis and its application in osteoporosis research. Sci. Rep. 2018 8 1 668 10.1038/s41598‑018‑19196‑2 29330445
    [Google Scholar]
  28. Zhao C.H. Li S.C. Li P.H. Research progress of signal molecules regulating osteoclast function. Zhongguo Guzhi Shusong Zazhi 2021 27 9 1361 1365
    [Google Scholar]
  29. Zhou Y. Zheng S.C. Shao H.B. Discussion on the mechanism of bone marrow mesenchymal stem cells in repairing alveolar bone defects in osteoporotic rats based on TGFβ1/Smad signaling pathway. Clin. J. Stomatol. 2023 39 11 643 648
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073388008251008041439
Loading
Potential Mechanism of Gumibao Decoction in Treating Glucocorticoid-induced Osteoporosis Based on Network Pharmacology and Experimental Verification
Bentham Science Publishers ; https://doi.org/10.2174/0113862073388008251008041439
/content/journals/cchts/10.2174/0113862073388008251008041439
/content/journals/cchts/10.2174/0113862073388008251008041439
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: rheumatic diseases ; rheumatoid arthritis ; glucocorticoid-induced osteoporosis ; network pharmacology ; Gumibao decoction ; bone mineral density

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